6. ANTIINFECTIVE DRUGS

6. 1 Anthelminthics

6.1.1.   Intestinal Anthelminthics

ALBENDAZOLE

General   Information

Drug Code                        Preparation                                                          Strength

         479                         Suspension Albendazole                                           400 mg/ 10ml

         447                         Tab. Albendazole                                                     400 mg

Description of the Drug

Albendazole is a broad speturm anthelmintic agent, belonging to the benzimidazole group of drugs.

Mode of Action

Synthesis of the parasite’s microtubules and also by decreasing glucose uptake. It is larvicidal in hookworm infections and ovicidal in ascariasis, ankylostomiasis, trichuriasis.

Pharmacokinetics

Albendazole is poorly absorbed from the gastro-intestinal tract, but if administered with a fatty meal, absorption increases.  Undergoes first-pass metabolism.  It has a plasma half –life of about 8.5 hours.  Absorbed drug is metabolized in liver and excreted in urine as both active and inactive metabolites.

Clinical  Information

Indications

·    Intestinal nematode infections (ascariasis, enterobiasis, strongyloidasis, ankylostomiasis, necatoriasis and trichuriasis) for prevention of symptoms.

·    Cestode infections (hydatidcyst, taeniasis, neurocysticercosis).

·    Cutaneous larva migrans.

Dosage – 5 mg/kg

Ascariasis, hook worm infections  or trichuriasis.

A single dose of 400 mg is given for adults and children above 2 years, may be repeated after 3 weeks.

Strongyloidiasis and Taeniasis

400 mg daily for 3 consecutive days, repeated after 3 weeks if necessary.

Enterobiasis

Adults – 400 g single dose, repeated after 2 days.

Children aged 2 years or more – 100 mg repeated after 7 days.

Cutaneous Larva migrans

400 mg daily for 3 to 5 days.

Neurocysticercosis

15 mg per kg daily for one month, in 2 divided doses.

Hydatid disease

10-15 mg per kg daily or 400 mg twice daily for adults given for a 28 day cycle with a 2 week interval between cycles. The number of cycles ranges from 1-12, though 3 cycles might be sufficient for most cysts.

Routes of Administration     Oral.

Contraindications

·    Pregnancy.

·    Children less than 2 years.

·    Cirrhosis and hepatic failure.

Precautions / Practice points

·    Monitor the liver function tests and blood counts prior to and every 2 weeks during thereapy.

·    When administered for neurocysticerosis adminster appropriate steroid and anticonvulsants as adjunctive measures.

·    3 weeks after treatement, examine fecal specimen for ova or cysts.  If positive, retreat the patient.

·    Administration Instructions:

-     Administer on empty stomach for luminal parasites, with fatty meal ( which increases absorption) for tissue parasites.

Drug Interactions

Non fatal:

·    Dexamethasone and praziquantel enhances effects of albendazole by increasing the serum levels.

·    Albendazole may increase clearance of carbamazepine.

Adverse Effects

Common effects:

·    Abnormal liver function tests and liver dyfunction.

·    GIT – abdominal pain, nausea, vomiting.

·    Leukopenia and granulocytopenia.

Rare effects:

·    CNS – headache, dizziness, vertigo, disorientation, raised intracranial tension.

·    Hypersensitivity reactions – rash or urticaria may occur.

Drug Toxicity

Diarrhoea, vomiting, tachycardia, respiratory distress.

Treatment of Toxicity

Gastric lavage and activated charcoal.

Storage

Store in dry place. Drug is very sensitive to humidity.

Shelf Life                     3  years.

6.1.2.   Anti Filarials.

DIETHYL CARBAMAZINE CITRATE

General   Information

Drug Code                        Preparation                                                Strength

         448                         Tab. Diethylcarbamazine citrate                    100 mg

         4876                       Syrup. Diethyl carbamazine citrate                100 mg/5ml

Description of the Drug

It is a synthetic piperazine derivative, active against filarial adult as well as  microfilariae.

Mode of Action

It acts by immobilizing and sensitizing the microfilarias making them more susceptible to phagocytosis and other host mechanisms.

Pharmacokinetics

It is readily absorbed from the GIT. Plasma half life is 2-3 hours.  It is widely distributed in tissues and is excreted in the urine both as unchanged as well as metabolites.

Clinical  Information

Indications

·    Lymphatic filariasis due to W.bancrofti, Brugia malayi and B.timori.

·    Tropical Eosinophilia.

·    Loasis due to Loa loa.

·    Larva migrans – cutaneous and visceral.

Dosage – 5 mg/kg

·    For filariasis – 6 mg/kg/day in 3 divided doses for 3 weeks.

·    For tropical eosinophilia – 2 mg/kg/day thrice daily for 1 week.

·    For larva migrans – 6 mg/kg/day in 3 divded doses for 7-10 days.

Routes of Administration  Oral.

Contraindications

·    Severe renal failure.

·    Elderly, debilitated and hypertensive patients.

Precautions / Practice points

·    Treat malnutrition and anemia in the patient, apart from antifilarial theraphy.

·    If patients are suspected to have malaria, antimalarial therapy should first be administered, then only DEC should be started.

·    Dosage to be adjusted inmild or moderate renal dysfunction.

·    Corticosteroids and antihistaminics to be given during first few days of treatment to reduce symptoms of allergic reaction to the dying parasites.

Drug Interactions

            Causes hypermotility of uterus by interacting with prostaglandins.

Adverse Effects

·    They are rare and usually mild and transient.

·    GIT – nausea, vomiting, anorexia.

·    CNS – headache, dizziness, drowsiness.

·    Allergic reaction from the death of thefilarial worms or microfilariae like fever, malaise, rashes, headache, arthralgia, GI symptoms leucocytosis.

Drug Toxicity

Fatal complications like tachycardia, hypotension, shock and death may occur when DEC given for heavy infestation of onchocerciasis and loasis.

Treatment of Toxicity

Symptomatic and supportive line of management.

Storage

Store in cool, dry, dark place.

Shelf Life                     2  years.

COUMARIN

General   Information

Drug Code                        Preparation                                                Strength

         478                         Tab. Coumarin                                                200 mg

Description of the Drug

It is 5,6 Benzo Alpha Pyrone.

Mode of Action

It activates the macrophages and increases the clearance of proteins from the extracellular space.  Hence, it prevents accumulation of proteins in extracellular space, which leads to fibrosis and obliteration of lymph vessels.

Pharmacokinetics

Well absorbed orally with 80% bioavailability.  Widely distributed, plasma protein binding is present. Metabolized in liver and excreted in urine as glucoronide conjugates.

Clinical  Information

Indications

·    Filarial Lymphoedema.

·    Post radiation lymphoedema and post block dissection lymphoedema of upper and lower Limbs.

·    Chronic venous insufficiency, varicose veins.

Acute:

Post traumatic and post operative swellings.

Dosage – 5 mg/kg

200   Mg twice daily after food.

Routes of Administration  Oral.

Precautions / Practice points

·    Liver function tests should be done prior to and during prolonged therapy.

·    When given for treatment of longstanding lymphoedema, effects are seen only 4-6 weeks after initationof therapy.

Adverse Effects

·    Slight dizziness, headache, mild nausea, diarrhoea or constipation.

·    Rare effects : Hepatotoxicity may occur.

Storage

Store in cool, dry, dark place.

Shelf Life                     2  years.

6.2       Antibacterials.

COTRIMOXAZOLE

General   Information

Drug Code                        Preparation                                                Strength

         4                        Cotrimoxazole oral suspension                     50 ml/bottle ; 5 ml

                                                                                                  containing 40 mg+200 mg

         5                          Tab.  Cotrimoxazole                                  80 mg Trimethoprim +

          400 mg of sulphamethaxazole.

        438                      Cotrimoxazole Tab. (Pediatric)          40 mg Trimethoprim +

                                                                                                200 mg sulphamethoxazole

Description of the Drug

Cotrimoxazole is a combination of the sulphonamide sulphamethoxazole with trimethoprim in the proportion of a 5 to 1.

Mode of Action

Both the componenets of the drug inhibit bacterial folic acid sythesis, but at a different stage in the metabolic pathway.  Sulphamethoxazole inhibits the conversion of PABA to dihydrofolic acid and trimethoprim inhibits dihydrofolate reductase enzymes which converts dihydrofolic acid to tetrahydrofolic acid, which is important for DNA synthesis.

Spectrum of action:

E, coli, Klebsiella, Enterobacter, Proteus, H. influenza, strep, pneumoniae, Shigella,
Salmonella, Pneumocystis carinii.

Pharmacokinetics

It is  well absorbed when given orally and widely distributed.  It penetrates CNS and CSF well.  Above 30-50% is protein bound . It has a half-life of ten hours hence, twice daily dosage is sufficient. Metabolized in the liver, excreted in urine, both as unchanged drug and as metabolites.

Clinical  Information

Indications

·    Uncomplicated urinary tract infections caused by susceptible organisms.  E.coli, Klebsiella, Enterobactoer, Proteus.

·    Gastro enteritis – caused by Cholera, Salmonella, Shigella.

·    Pneumocystis carinii pneumonia in AIDS patients – both for treatement and prophylaxis.

·    Otitis media, upper respiratory tract infection, chronic bronchitis, sinusitis and pneumonias, caused by susceptible strains of H. influenza and Streptococcus.

Dosage – 5 mg/kg

·    For uncomplicated urinary tract infection – single dose of 960 mg.

·    Other infections:

Adutls – 960 mg twice daily.

Children – Trimethoprim 8 mg/kg and sulphamethoxazole 40 mg/kg – 12 hourly.

·    Pneumocystis carinii infections – 20 mg/kg of trimethoprim and 100 mg/kg of methaxafole – 12 hourly.

For prophylaxis of Pneumocystis carinii infection in neutro penic patients – 10 mg/kg/day of trimethoprim neatro with 50 mg/kg/day of suphamethoxazole in 2 divided doses, 3 days in a week Duration  10 days.

Routes of Administration  Oral.

Contraindications

·    Pregnancy, nursing

·    Severe renal failure.

·    Megaloblastic anemia due to folate deficiency.

·    Sulpha drug allergy and hypersensitivity to trimethoprim.

·    Infants below two months.

Precautions / Practice points

·    Use with caution in elderly, renal and hepatic dysfunction risk of adverse effects are more.

·    Chronic alcoholics, malnutrition and patients with malabsorption, (states of a possible folate deficiency). In these patient groups, megaloblastic anemia may be precipitated due to its action as a folate antagonist.

·    Discontinue the use of the drugimmediately if signs of sensitivity (skin rashes) develop.

·    For dosage adjustments in renal failure see appendix.

·    Administration Instructions:

-     Take one hour before meals with water on an empty stomach.

-     Ensure adequate fluid intake and urinary output to prevent crystalluria.

Drug Interactions

Potenitally fatal:

·    Enhances effects of sulphonyl ureas – hypoglycemic episodes may be precipitated.

·    Risk of ventricular arrhythmias with amiodarone is increased when cotrimoxazole is administered.

·    Increased action of oral anticoagulants with risk of major bleeding episodes.

Nonfatal:

·    Antifolate effects of pyrimethamine, phenytoin and methotrexate are increased.

·    Effects of thiazide diuretics may be blunted.

·    Nephrotoxicity of cyclosporin is increased.

Adverse Effects

Common effects :

·    GIT – nausea, vomiting, anorexia.

Rare effects:

Bone marrow – megaloblastic anemia due to folate antagonism,bone marrow depression, agranulocytosis, leucopenia, haemolysis in G6PD deficient persons.

·    Hypersensitivity:

Drug fever, vasculitis, Henoch scholein purpura, serum sickness like syndrome.

Allergic skin reaction – Steven Johnson’s syndrome, exfoliative dermatitis, toxic epidermonecrolysis.

·    Hepatitis :

Fulminant hepatic necrosis can occur.

Drug Toxicity

·    Anorexia, colicky pain, nausea, vomiting, dizziness, drowsiness, headache, pyrexia, haematuria and crystatlluria may be present.  At a later stage jaundice may appear.

·    Bone marrow suppression, megalobastic anemia.

Treatment of Toxicity

·    Gastric lavage and emesis to remove the unabsorbed poison.

·    Continuous monitoring of electrolyte balance, blood counts.

·    Symptomatic treatment.

Storage

Store in well closed, light resistant container in a cool dry place.

Shelf Life                     2  years.

AMPICILLIN

General   Information

Drug Code                        Preparation                                                Strength

37                             Inj. Ampicillin                                            500 mg / vial

                                          Cap. Ampicillin                                          250 mg

Description of the Drug

Ampicillin is an amonopenicillin – a semisynthetic, a broad spectrum, orally active penicillin.  It is a bactericidal agent.

Mode of Action

Ampicillin inhibits peptidoglycan production, hence interferes with bacterial cell wall synthesis, thereby causing death of the bacteria.

Spectrum

It is not effective against penicillinase producing staphylococci, some strains of H. influenza and E.coli have developed resistance to it.

Gram positive:

Streptococcus, Preumococci, Non-penicillinase producing Staphylococci, Bacillus anthracis, Clostridium species, Corynebacterium species, Enterococci, Listeria.

Gram negative:

H. influenza, Neisseria gonorrhoea, Neisseria meningitides, Proteus mirabilis, Salmonella, Shigella, E.coli.

Others :

Actinomycetes.

Pharmacokinetics

Ampicillin is about 50% absorbed from the gastro-intestinal tract after oral administration.  Plasma half-life is about 1-1.5 hours, necessitating a 4 times a day dosage schedule.
Ampicillin is excreted in the urine mainly unchanged.

Clinical  Information

Indications

·    Respiratory tract infections – sinusitis, bronchitis and lower respiratory infections by susceptible organisms like H.influenza, Pneumococci etc.

·    Urinary tract infections by susceptible bacteria like Proteus.

·    GIT infections – diarrhoea and dysentery caused by susceptible strains of Shigella, E.coli, Proteus, Enterococci.

·    Salmonella infections.

·    Gonococcal infections.

Intravenous Preparations are indicated in:

-  intra abdominal infections, cholecystitis, peritonitis etc.

-  skin, soft tissue bone or joint infections due to susceptible organisms.

-  Uncomplicated urinary tract infections caused by susceptible organisms.  E.coli, Klebsiella, Enterobactoer, Proteus.

Dosage

Usual dose:

·    Parenteral:

Adult – 500 mg 6th hourly, can be increased upto 6-10 gm/day in severe infections.

Children – 100 mg/kg/day in 4 divided doses, can be increased upto 400 mg/kg/day in severe infections.

·    Oral :

Adult – 500 mg 6th hourly, upto 4-6 gm/day.

Children – 50-100 mg/kg/day in  4 divided doses, maximum 2-3 gm/day.

Duration  - 10-15 days.

Routes of Administration  Oral  I.M.,   I.V..

Contraindications

             Known allergy to penicillin.

Precautions / Practice points

·    Use with caution in patients with infectious mononucleosis renal impairment, leukemia, and HIV infection – incidence of ampicillin rash is more.

·    For broad-spectrum empirical therapy it can be given with an aminoglycoside antibiotic.

·    For streptococcal infections give for atleast a minimum of 10 days to eradicate infection.

·    For reduction of dose in renal failure, see appendix.

·    Administration Instructions:

-  Give oral capsules one hour before meals.

-  Do not mix with aminoglycosides like gentamicin in the same syringe or IV set.  Use only sterile water or normal saline for reconstitution and use the reconstituted solution within 2 hours.  Do not use dextrose or dextrose containing solution for administering infusions due to limited stability. Maximum concentration of solution to be 50 mg/ml i.e use 10 ml of sterile water to dilute one vial (500 g).  If concentration is more, stability of solution may be compromised.

Drug Interactions

Nonfatal:

·    Renal clearance of ampicillin is retarded by the concomitant administration of probenecid.

·    Should not be given with bacteriostatics like erythromycin wich interferes with the action of ampicillin by decreasing the multiplication of organisms.

·    Amplicillin may decrease the efficacy of estrogen-containing oral contraceptives.

Adverse Effects

Common effects :

·    Gastro-intestinal adverse effects – nausea, vomiting, diarrhoea due to overgrowth of non susceptible organisms.

·    Skin rashes – erthematous maculopapular eruptions are characteristic of amplicillin toxicity and often appear days after commencing treatment.  Starts on the trunk and spreads throughout the body.  This is nonallergic rash and must be differentiated from a hypensensitivity reaction.  Does not requires termination of therapy.

Rare effects:

·    Psuedomembrancous colitis can occur due to overgrowth of clostridium difficle.

·    Hypersensitivity reactions.

·    Mild elevation of liver enzymes.

·    Anemia, leucopenia, thrombocytopenia.

Drug Toxicity

Rare – only in exceedingly high doses, gastro-intestinal distress, signs of neuromuscular irritability due to penicillin toxicity may occur.

Treatment of Toxicity

Discontinue the drug, emesis and lavage if ingested, supportive and symptomatic treatment.

Storage

Keep in a cool place.  Store at a temperature not exceeding 30 C in air tight containers.

Shelf Life

Ampicillin injection                  -    24 months.

Ampicillin Capsules                            -    24 months.

BENZYL PENICILLIN

General   Information

Drug Code                        Preparation                                                Strength

38                             Inj. Benzyl Penicillin                                     10 lacs

Description of the Drug

Benzylpenicillin is a beta-lactam antibiotic whose antibacterial activity is due to the
presence of 6 amino penicillanic acid in its structure.

Mode of Action

Benzyl penicillin is a bactericidal agent, which binds to penicillin binding proteins in the organisms and interferes with the synthesis of bacterial cell wall mucopeptide, peptidoglycan, rendering the cell wall unstable and thereby killing the cell.

Spectrum of action:

Staphylococci (which do not produce penicillinase), Streptococci, Pneumococci, Neisseria gonorrhoea, Neisseria meningitides, Corynebacterium,  B. anthracis, Clostridia, Actinomycetes, Listeria, Leptospirosis, Treponema, Enterococci.

Pharmacokinetics

Benzyl penicillin is rapidly absorbed following intramuscular injection.  Cannot be given orally because it is unstable to gastric acid.  It is widely distributed.  It does not cross the blood brain barrier in healthy patients but in meningitis adequate levels are found in the CSF.  It is metabolized to a limited extent and excreted in the urine by tubules mostly unchanged.  Plasma half life is ½-1 hour ( increased in renal dysfunction).

Clinical  Information

Indications

·    Bacteremia, empyema, pneumonia, pericarditis, infective endocarditis, meningitis caused by streptococcus.

·    Pneumococcal pneumonia.

·    Meningococcal meningitis.

·    Diphtheria.

·    Tetanus and other clostridical infection like gas gangrene.

·    Gonococcal infections – genito urinary infection, meningitis, disseminated infections.

·    Syphilis.

·    Actinomycosis.

·    Fusospirochaetal infections.

·    Listeria, pasturella, anthrax  infections.

Dosage

            Note  : One million units = 0.6 g

Adult  :

Streptococcal endocarditits

Two million units, IV, 4th hourly, usually with an aminoglycoside antibiotic for

atleast 4 weeks.

Neurosyphilis  : 2 to 4 million units, IV, 4th hourly for 10-14 days.

            Duration  - 10-15 days.

Children

            Usual dose 1-4 lakhs/kg/day – 4th hourly for 10-14 days, May be increased in serious and severe infections.

Routes of Administration 

            Intramuscular, Intravenous – continuous or intermittent.

Contraindications

             Known allergy to penicillin.

Precautions / Practice points

·    Administer only after test dose.

·    For dosage reduction in renal failure, see appendix.

·    Administration Instructions:

-     when giving IV, avoid small veins, vessels near nerves and take care to prevent intraarterial injection.

-     Do not mix aminoglycosides or any other substance, as penicillins are incompatible with most solutions.  Always use a separate syringe.

-     Diluents for infusion is to be normal saline or 5% dextrose.

-     When giving IM, upper outer quadrant of buttock is preferred.

Drug Interactions

Nonfatal:

·    Probenecid prolongs the half life of benzyl penicillin by competing with it for renal tubular secretion:

·    Concurrent administration of bacteriostatic drugs like erythromycin and tetracycline reduces the effectiveness of penicillin by decreasing active multiplication of bacilli.

Adverse Effects

Common effects :

·    Local pain on IM administration.

Rare effects:

·    Most important is allergy to the drug which is rare (incidence – 0.5%) resulting in

·    Hypersensitive reactions – urticaria, skin rashes, edema, angioneurotic edema, bronchospasm, respiratory distress and collapse.

·    Serum sickenss like reaction – fever, joint swelling, chills, oral lesions, vasculitis,
eosinophilia, haemolytic anemia and interstitial nephritis.

·    Jarisch Hexheimer reaction in syphilitic patients.

·    Large IV doses may inhibit platelet aggregation and cause thrombocy topenia.

Drug Toxicity

·    Only at doses more than 20 millions units/day.

·    CNS  - convulsions, cerebral irritation, signs of neuromuscular irritability – tremors, asterixis etc.

·    Electrolyte disturbances – hyperkalemia, when potassium salts are used.

Treatment of Toxicity

·    Haemodialysis to remove excess drug.

·    Symptomatic treatment.

Storage

Store below 30o C. Drug is very sensitive to light.

Shelf Life                     -    2 years.

BENZATHINE  PENICILLIN

General   Information

Drug Code                        Preparation                                                Strength

39                             Inj. Benzathine  Penicillin                            12 lakhs/vial

Description of the Drug

Benzathine penicillin is a beta-lactam antibiotic, a salt of penicillin with a prolonged
duration of action.

Mode of Action

Benzathine  penicillin acts by interfering with peptidoglycan formation and bacterial cell wall synthesis.  It is a bactericidal drug.

Spectrum of action:

Staphylococci (which do not produce penicillinase), Streptococci, Pneumococci, Neisseria gonorrhoea, Neisseria meningitidis, Corynebacterium,  B. anthracis, Clostridia, Actinomycetes, Listeria, Leptospirosis, Treponema, Enterococci.

Pharmacokinetics

When benzathine  penicillin is given by intramuscular injection it forms a depot from which it is slowly absorbed from the site of injection.  Hence, onset of action is slow (12-24 hours) but prolonged (15-20 days).  The drug is excreted by the kidney, mostly unchanged.

Clinical  Information

Indications

·    Treatment of     MILD TO MODERATELY severe infections due to penicillin G susceptible organisms.

·    Moderate infections of upper repiratory tract, caused by streptococci.

·    Syphilis early and latent stages, yaws, bejel.

·    Prophylaxis of rheumatic fever, chorea and glomerulo nephritis.

Dosage

For early syphilis (less than one year duration).

Single dose 2.4 million ( 24 lakhs) single dose.

Latent syphilis ( more than one year duration).

2.4 million/week for 3 weeks.

Congenital syphilis

            50000 units/kg.

Other treponemal infections (Yaws, pinta and endemic syphilis (bejel)

Adult  :

12 lakhs single dose.

Children

            < 30 kg – 3-6 lakhs.

> 30 kg – 9 lakhs.

Duration – 1 day.

To prevent reoccurrences of acute rheumatic fever

            12 lakhs every 4 weeks or 6 lakhs every 2 weeks.

Routes of Administration    I.M.

Contraindications

             Known allergy to penicillin.

Precautions / Practice points

·    Administer only after test dose.

·    Administration Instructions:

-     Do not administer near artery or nerve, upper outer quadrant of gluteal region is preferred.

-     Do not give IV, SC or itrarterially.

-     Do not dilute the solution.

Drug Interactions

Nonfatal:

·    Probenecid given concomitantly decreases the renal clearance.

·    Other bacteriostatc drugs like tetracycline, erythromycine decreases the efficiency of drug by decreasing the active multiplicity of bacilli.

Adverse Effects

Common effects :

·    Local pain on IM administration.

Rare effects:

·    Hypersensitivity reactions, especially skin rashes.  Anaphylaxis can occur in susceptible persons – urterica, edema, fever, eosinophilia, serum sickness like reactions, chills, fever, edema, arthralgia.  Treat with oxygen, epinephrine and IV steroids.

·    Some patients with syphilis may experience a Jarisch Hexheimer reaction shortly after starting treatment with penicillin which is probably due to the release of endotoxins from the killed treponemes.  Symptoms include fever, chills, headache and reactions at the site of lesions.  The reaction can be dangerous in cardiovascular syphilis or where here is a serious risk of increased local damage such as in optic atrophy.

·    If injected into an artery, severe neurovascular damage may occur with gangrene requiring amputation of digits.  If injected near nerve, permanent neurological damage may occur.

·    Quadriceps femoris fibrosis and atrophy can occur after repeated injections.

Drug Toxicity

Neuronal hyperirritability, tremors, agitation, hallucinations, confusion, even fits may occur.

Treatment of Toxicity

·    Symptomatic and supportive therapy.

·    Haemodialysis may help in removing the drug.

Storage

Store in a cool dry place.

Shelf Life                     -   36 months.

CEPHATAXIME SODIUM

General   Information

Drug Code                        Preparation                                                Strength

       226                            Inj. Cephataxime Sodium                               1 g/vial

40                             Inj. Cephataxime Sodium                            250 mg vial

Description of the Drug

Cephataxime Sodium is a third-generation cephataxime cephalosporin antibiotic.

Mode of Action

Cephataxime is a bactericidal drug, an inhibitor of peptidoglycn synthesis.  It thereby intereferes with bacterial cell wall synthesis and kills the organism.

Spectrum of action:

Wide range of both gram positive and gram negative organisms.

Gram positive :

Streptococci, Staphylococci (both penicillinase and nonpenicillinase producing species ), Pneumococci.

Gram negative :

E.coli, H. influenza, Klebsiella, Neisseria, Proteus, Serratia, Moracella catarrhalis, Salmonella, Shigella, Yersinia.

Others :

Bacteroids, Clostridium, Peptococcus, Fusobacterium. Moderatly active against pseudomonas.

Pharmacokinetics

The drug must be administered parenterally because of poor oral absorption.  It is widely distributed, CSF penetration is good.  It is partially metabolized in the liver and excereted through the kidneys.

Clinical  Information

Indications

·    Lower respiratory infections : (bronchitis and pneumonias) caused by Streptococcus pyogenes, Pneumococcus, Staphylococcus aureus, E.coli, Klebsiella, H. parainfluenza, H. influenza, Proteus and Pseudomonas.  Also epiglottitis caused by H.influenza.

·    Urinary tract infection – caused by susceptile strains of Staphylococcus epidermidis, Staphylococcus aureus, Enterabactor, Citrobactor, E.coli, Proteus, Pseudomonas, Klebsiella.

·    Infection caused by Neisseria gonorrhoea.

·    Gynaecological – pelvic inflammatory disease, endometritis caused by susceptible species.

·    Gram negative septicaemia by E.coli, klebsiella etc.

·    Skin and deep seated infections caused by Staphylococcus and Streptococcus.

·    Intraabdominal infection, biliary tract infections, Peritonitis caused by E.coli, Streptococci, Klebsiella, Proteus and other susceptible organisms.

·    Bone and joint infection by Staphylococci.

·    Bacterial meningitis caused by Neisseria meningitides, H.influenza, Streptoocci, Klebsiella, E.coli and other susceptible species.

·    Prevention of infection in patients of

-     Abdominal and vaginal hysterectomy.

-     G.I surgery.

-     Genitourinary surgery.

-     Lower section caesarean section.

Dosage

Adult  :  Usual dose :  2-6 gram daily in 2 divided doses.  In severe infections (septicaemia, meningitis etc.) –2 gm IV every 4,6 hours.

Children – 1-12 years.

            < 50 kg – like adults.

             > 50 kg – 100-150 mg/kg/day in 2-3 divided doses.

Neonates : 50 mg/kg/dose IV 12th hourly.

Gonorrhoea : Single 1 g dose IM/IV.

For surgical prophylaxis 1 g 30-90 minutes before surgery.

Duration – 10 days.

Caesarean section

            1 g given intravenously to the mother as soon as the umbilical cord is clamped and two further doses I.M. or I.V 6-12 hours later.

Routes of Administration    IV,    I.M.

Contraindications

·    Individuals allergic to penicillin and cephalosporins.

·    Severe renal failure.

·    Porphyria.

Precautions / Practice points

·    Use with caution in pregnancy and lactation.

·    Adjust the dose in renal dyfunction (see appendix)

·    Monitoring of patients for superinfection and immediate treatment is essential.

·    It treated for more than 10 days, blood counts to be checked regularly.

·    May give false positive tests for urine sugar by glucose oxidase strips or Benedicts tests and may give false positive Coomb tests.

·    Administration Instructions:

-     Headache and arrhythmias can develop if given intravenously too rapidly.  Hence, administer slowly over 3-5 min.

-     Do not mix aminoglycosides in same syringe.

-     If IV infusion is setup, reconstitute only in normal saline or 5% dextrose and use immediately.

-     Reconstituted solutions are stable for 12 hours in room temperature and for 24-48 hours if refrigrated.

Drug Interactions

Nonfatal:

·    Probenecid  decreases the renal excretion and may prolong the serum levels.

·    Frusemide and aminoglycosides may increase the risk of interstitial nephritis.

Adverse Effects

Common effects :

·    Thrombophlebitis following I.V. infusion, irritation if perivascular extravasation, pain and tenderness on IM site.

Rare effects:

·    Prolonged use may result in overgrowth of non-susceptible organisms. Pseudomembranous colitis may develop.

·    Hypersensitivity reactions, especially skin rashes, utricarid,  eosinophilia, fever reactions resembling serum sickness and anaphylaxis.

·    GIT – nausea, vomiting, diarrhoea, colitis.

·    Interstitial nephritis and renal damage may occur.

·    Disulfiram like reaction, agranulocytosis, neutropenia, leukopenia, eosinophilia.

Drug Toxicity

Drug fever, anaphylaxis, diarrhoea, nausea, vomiting.

Treatment of Toxicity

·    Supportive and Symptomatic .

Storage

Store at temperature not exceeding 25 C. Protect from the light.

Shelf Life                     -   2 years.

CIPROFLOXACIN

General   Information

Drug Code                        Preparation                                                Strength

       42                            Inj. Ciprofloxacin I.V                                     200 mg

       231                          Lab. Ciprofloxacin                                           500 mg

Description of the Drug

Ciprofloxacin is a broad spectrum antibacterial agency belonging to the fluroquinolone group of drugs.

Spectrum of Action:

Gram postive:

            Staphylococcus epidermidis.

            Steptococcus preumoniae

            Streptococcus pyogenes

            Staphylococcus aureus.

Gram negative :

E.coli, Salmonella, Shigella, H. influenza, Klebsiella, Serratia, Proteus, Pseudomonas, Moracella, Neisseria, Campylobacter, Enterobacter, Citrobacter and Yersinia.

Others     - Chlamydia, Trachomatis, Mycobacterium tuberculosis.

Mode of Action

Ciprofloxain inhibits the replication of bacterial DNA by interfering with the action of DNA gyrase during bacterial growth and reproduction.  It is a bactericidal agent.

Pharmacokinetics

Ciprofloxacin is rapidly and well absorbed from the gastro intestinal tract.  Plasma half life is about 4 to 5 hours but a twice daily dosing schedule is adequate.  It is eliminated principally unchanged by tubular secretion.  About one third of elimination is by hepatic metabolism and biliary excretion.

Clinical  Information

Indications

·    Respiratory tract:

-     Acute sinustitis caused by H.influenza, Morakella catarrhalis.

-     Lower respiratory infections, chronic bronchitis etc. caused by H.influenza, Streptocaccus pneumoniae, gram negative bacteria like E.coli, Proteus, Pseudomonas, Klebsiella, Enterobacte etc.

-     Nosocomial Pneumona (Klebsiella, H. influenza)

·    Urinary tract infection  (complicated and uncomplicated episodes).

-     caused by E.coli, Klebsiella, Enterobacter, Proteus, Pseudomonas, Serratia and other susceptible organisms.

-     Chronic bacterial prostatitis caused by E.coli, Proteus mirabilis.

·    GIT

-     Infections diarrhoea caused by E.coli, Campylobacter jejuni, Shiegella.

·    Typhoid and paratyphoid fevers by Salmonella species.

Others:

·    Intraabdominal and peritoneal infections, skin and soft tissue infections, bone and joint infections by susceptible organisms.

·    Cervical and urethral gonorrheal infections.

Dosage

For severe infections (severe lower respiratory infections, complicated urinary tract infections, complicated, intraabdominal infections, bone and joint infections)

Orally – 500 mg –750 mg 12th hourly (maximum of 1.5 gm/day).

IV –200-400 mg 12th hourly (maximum of 800 mg/day). Treat for 2-6 weeks depending on the severity of infection.

For sinusitis, uncomplicated or mild urinary tract infection.

Orally –250 mg 12th hourly.

IV – 200 mg 12th hourly for 7-10 days .

For Typhoid

Orally – 500 mg 12th hourly for ten days.

IV – 200 mg IV 12th hourly for 10-14 days.

For gonorrhoea

Orally – single dose of 500 mg

Normal duration is 7-10 days, but in resistant TB duration is prolonged.

Routes of Administration   Oral ,  IV,   

Contraindications   Known hypersensitivity

Precautions / Practice points

·    Avoid use in pregnancy, lactating mothers, children and adolescents less than 18 years because fluroquinolones produce erosion of immature cartilage.

·    Should be used with caution in patients with epilepsy or a history of CNS disorders ( can cause increased intracranial tension and may precipitate convulsions).

·    An adequate fluid intake should be maintained during treatment because of the risk of crystalluria.

·    Do not drive or operate machinery as ciprofloxacin may impair the performance of skilled tasks.  Also abstain from alcohol as its CNS effects are enhanced by alcohol.

·    Avoid ecess exposure to sunlight or wear sunscreens due to risk of photosensitization.

·    Adjust dose in renal failure (see appendix).

·    Instruct the patients to report immediately if pain or inflammation of tendon occurs.

·    Administration Instructions:

-     Oral : Give one hour before meals.  Do not give antacids and minerals simultaneously.  Give plenty of water to maintain hydration.

-     I.V. : Give infusion over 30-60 min.  Do not exceed the supplied concentration of 2mg/ml or mix with other drugs.

Drug Interactions

Potentially fatal:

·    Ciprofloxacin decreases the clearance of theophylline and caffeine.  Seuzires can occur if ciprofloxacin and theophylline are given concomitantly.

·    Nephorotoxicity of cyclosporin is increased.

·    Effects of oral anticoagulants may be enhanced.

Non fatal:

·    The absorption of ciprofloxacin is reduced by antacids containing  aluminium or magnesium.  Dairy products with high calcium content, iron Preparations, sucralfate and zinc salts reduce the absorption of ciprofloxacin.

·    Urinary excretion of ciprofloxacin is reduced by the concomitant administration of  probenecid.

Adverse Effects

Common effects :

·    Gastro-intestinal disturbances include nausea, vomiting, diarrhoea, abdominal pain.

·    Pain and irritation may occur at the site of injection when given IV.

·    Pseudomembranous colitis and superinfection with fungi may occur.

·    CNS – headache, dizziness, reatlessness, drowsiness or insomnia.

·    Musculoskeletal tendonitis and tendon repture.

·    Hypersensitivity type ……………..

Drug Toxicity

Sings of CNS stimulation, headache, siual disturbances, hallucination, seizures can occur, with acute renal failure.

Treatment of Toxicity

Vomiting and gastric lavage.

Storage

Store at airtight container protected from light.

Shelf Life

Ciprofloxacin injection – 2years.

Tab. Ciprofloxacin – 4 years.

CLOXACILLIN

General   Information

Drug Code                    Preparation                                                Strength

       43                            Inj. Cloxacillin                                               250 mg

       52                            Cap. Cloxacillin                                             250 mg

Description of the Drug

Cloxacillin is an antibiotic of the penicillin group, which is penicillinase resistant, as well as acid stable.  Its action is however, less potent than that of penicillin.

Mode of Action

Cloxacillin interferes with the formation of peptigoglycan necessary for bacterial cell wall synthesis.  Specturm of action is similar to penicillin G ( mostly gram positive organisms) but is primarily used for penicillinase producing organisms.  As it is less effective than penicillin it is not used aginst other orgainisms.

Pharmacokinetics

It is stable to acid medium and can be administered orally, but bioavailability is only 50%.  It is widely distributed. On IM administration, peak plasma levels occur 30-60 minutes after injection.  Duration of action is 6 hours, necessitating a 4 times daily dosage schedule.  The drug is metabolized to a limited extent and it is excreted in the urine and bile.

Clinical  Information

Indications

Treatment of infections due to penicillinase producting staphylococci resistant to benzyl penicillin.

·    Bone and joint infections, respiratory infections, soft tissue infections, urinary tract infections caused by penicillinase producing organisms.

·    Endocarditis, septicaemia etc.

·    Peritonitis – treatment as well as prophylaxis in patients on continuous ambulatory peritoneal dialysis.

·    Skin infection such as folliculitis, bullous impetigo furuncles etc.

Dosage

Usual dose (oral and parenteral)

Adults: 250-500 mg 6 hourly upto 4-6 gms/day.

Children ; 50-100 mg/kg/day in 4 divided doses, maximum of 4gm/day.

Duration – 7-10 days.

Routes of Administration    I. V.,  I.M.,  Oral.

Precautions / Practice points

·    With caution in patients with liver disorders – risk of hepatic side effects are more.

·    Should not be administered if patients is suspected to be allergic to beta lactam antibiotics.

·    Dosing intervals should be increased in renal dysfunction.

·    If given in elderly ( more than 55 years) and for more than two weeks, monitor liver function tests (SGOT and SGPT).

·    Administration Instructions:

- Give one hour before meals.

- When giving IV – give very slowly over five minutes.

Reconstitute only with sterile water and DO NOT MIX WITH ANY OTHER ANTIBIOTIC DRUGS.

Drug Interactions

Non fatal:

·    Probenecid reduces the renal clearance of the drug.

·    Cloxacillin may decrease the efficacy of oestrogen containing oral contraceptives.

·    When combined with bacteriostatic agents, its action may be decreased due to inhibition of active bacterial multiplication.

Adverse Effects

Common effects :

·    GI side effects – nausea, vomiting, diarrhoea.

·    Pain on IM administration, thrombophlebitis on IV administration.

Rare effects:

·    Hypersensitivity – skin rashes, drug fever anaphylactic shock in penicillin sensitive persons.

·    Cholestatic hepatitis and hepatic dysfunction.

·    Interstitial nephritis.

Storage

Store at temperature not exceeding 25o C in airtight containers. Not to be freezed.

After Preparation, the solution must be clear and must be used within 24 hours.

Shelf   Life                     2 years.

GENTAMYCIN

General   Information

Drug Code                        Preparation                                                Strength

       46                            Inj. Gentamycin                                               80 mg/2 ml

Description of the Drug

Gentamycin is an aminoglycoside antibiotic derived from Micromonospora purpurea.  It is effective mainly against gram negative organisms.

Mode of Action

It is a bactericidal agent, irreversibly inhibiting bacterial prote in synthesis bybinding to 30S subunit of ribosomes.  Its action is enhanced by antibiotic active against the bacterial cell wall like penicillin.

Specturm of Action.

Mostly on negative organisms like – Pseudomonas aeruginosa, vibrin cholera, Yersinia pestis, Francisella tularensis. Enterobacter jarogenes, Escherichia coli, Klebsiella pneumonia, Proteus, Serratia marcescens, moderately active against Staphylococcous aureus.

Pharmacokinetics

It is not absorbed orally.  After I.M. administration peak serum levels is reached in 30 min and lasts for about 6-8 hours.  It is concentrated in the renal cortex and in the endolymph and perilymph of the inner ear (accounting for nephrotoxicity and ototoxicity). It does not each effective concentration in he CSF.  It is excreted in the urine by glomerular filtration.

Clinical  Information

Indications

·    Gram negative septicaemia and neonatal sepsis.

·    CNS meningitis – along with a betalactam antibiotic.

·    In conjunction with penicillin, for treatment of Infective endocarditis caused by streptococci or enterococci.

·    Complicated urinary tract infections, bilary tract infections, peritonitis, prostatitis, pyelonephritis, respiratory tract infections like pneumonias caused by susceptible gam negative organisms.

·    Prophylaxis of infection in burns patients.

·    With carbenicillin in treatment of pseudomonas aerugirosa infection.

·    In empirical therapy of serious infections when causative organisms is unknown – in conjunction with a betalactam antibiotic.

Routes of Administration     I.M.,  or IV administration.

Dosage

Adults : 3-5 mg/kg/day in 3 divided doses 8th hourly  In case of life threatening infection, dose can be increased to 7mg/kg/day.

Neonates with severe infection – 7.5 mg/kg/day in two equally spaced injections ( 12th hourly).

Children : 5 mg/kg/day in 3 divided doses (8th hourly).

Duration – 7-10 days.

Contraindications

·    Severe renal dysfunction.

·    Allergy to gentamycin.

·    Prexistines hearing and vestibular problems.

·    Pregrancy – it crosses the blood barrier and causes irreversible, bilateral congenital deafness in the foetus.

·    Neuromuscular disorders like myasthenia gravis.

Precautions / Practice points

·    Monitor for nephrotoxicity if the patient is on the drug for more than 2 weeks; by periodic urine examination. Nephrotoxicity is mainifested by decrease in specific gravity, increase in urine proteins, presence of cells or casts, reduced creatinine clearance and increased blood urea nitrogen.  Nephrotoxicity is decreasd by proper hydration and adequate urinary output.

·    Ask patiet to report immediately if tinnitus or vertigo occurs and stop the drug at once. Monitor vestibular and cochlear function if on prolonged therapy.

·    Very high doses of gentamycin experimentally has caused neuromuscular blockade and respiratory paralysis. Hence, administer with caution in patients during anaestheisa on
neuromuscular blocking agents like d-tubocurarine etc.  I.V. calcium gluconate may be used if neuromuscular blockade occurs.

·    Gentamycin is not indicated for the treatment of uncomplicated urinary tract infection.

·    In burns patients, altered pharmacokinetics results in reduced serum concentration of the drug, hence dose adjustments must be done.

·    Dose adjustments to be made in renal dysfunction – divide the dose to be given, by serum creatinine level. If serum creatinine level is 2 mg – only 50% of the dose to be given (also see appendix).

·    Administration Instructions:

-     Give IV injections very slowly (over 3-5 min.) and concentration not exceeding 40 mg/ml.

-     DO NOT MIX WITH ANY OTHER DRUG (like ampicillin ) in the same syringe or IV set due to physical incompatibility.

-     If infusion is set up, diluents to be used are normal saline or 5% dextrose.

Drug Interactions

Potentially fatal:

·    Drugs which increases nephrotoxicity of gentamycin.

-  Cepholosporins.

-  Amphotericin

-  Other aminoglycosides.

-  Cisplatin, vancomycin etc.

-  Cyclosporin.

·    Gentamycin can potentiate neuromuscular blockade of skeletal, muscle relaxants like, d-tubocurarine.

Non fatal:

·    Ototoxicity of gentamicin is increased by diuretics like frusemide and ethacrynic acid.

·    Indomethacin increases the plasma levels of gentamicin.

·    Effects of nondepolarising muscle relaxants are enhanced.

Adverse Effects

            Are dose and duration dependent.

Ototoxicity – Both vestibular & cochlear.

            Headache, dizziness, vertigo, ataxia, hearing loss, tinnintus.

Other mainifestations of neurotoxicity – numbness, twitching of muscle, paraesthesias.

Nephrotoxicity – reversible if drug is withdrawn immediately.

            Acute tubular necrosis and interstitial nephritis may occur.

Neuromuscular blockade – curare like effect of gentamycin resulting in paralysis, respiratory paralysis and apnoea may occur.

Drug Toxicity

·    Signs of 8th  nerve dysfunction – tinnitus, vertigo.

·    Neurotoxicity – Encephalopathy, confusion, leathargy, hallurcinations, convulsions, mental depression.

Treatment of Toxicity

Adequate hydration to maintain a urine output of 3ml/kg/hour.  Haemodoalysis or peritoneal dialysis.  For neuromuscular toxicity – intravenous calcium gluconate administration should be done.

Storage

Keep below 30o C.

Store in airtight containers.

Shelf   Life                     16 months.

PROCAINE PENICILLIN

General   Information

Drug Code                        Preparation                                                Strength

       48                               Inj. Gentamycin                                              

                                          Procaine Penicillin                                         4 lacs/vial

Description of the Drug

It is a beta lactam antibiotic, the Preparation containing procaine penicillin and benzyl penicillin in the ration of  5:1

Mode of Action

Kills growing and dividing bacteria by inhibiting Peptidoglycan production and bacterial cell wall synthesis by interfering with formation of peptigolycan.

Specturm of Action.

Staphylococci (which do not produce penicillinase), Streptococci, Pheumococci, Nersseria gonorrhoea, Neisseria meningitides, Corynebacterium, Bacillus anthracis, Clostridia,
actinomycetes, Listeria, Leptospirochaetes, Treponema, enterococcus.

Pharmacokinetics

When given by IM injection, forms a depot from which the drug is slowly hydrolyzed to release benzyl penicillin.  The benzyl penicillin gives immediate plasma concentration, while procaine penicillin attceives aintains effective concentration of benzyl penicillin for 12-24 hours.  Most of the drug is excreted unchanged in the urine.

Clinical  Information

Indications

Treatement of  MODERATE TO SEVERE infections due to penicillin G susceptible organisms.

·    Moderate to severe infections of upper respiratory tract, caused by susceptible Pnemococci, Streptococci species.

·    Streptococal infections like scarlet fever, erysipelas.

·    Syphilis – latent stages and as an alternative to benzyl penicillin in neuro syphilis.

·    Uncomplicated gonorrhoea.

Dosage

Usual dose in respiratory infections.

·    Adult and children more than 30 g-0.6 – 2.4 million units, once or twice a day, depending on severity of infection.

·    Children less than 30 kg – 3-9 lakhs units.

Streptococcal infection – 6 lakhs units, IM, bd.

For neurosyphilis – 2.4 million units/day with probenecid 500 mg q.i.d. oral for 10-14 days.

Uncomplicated gonorrhoea single dose of 4.8 million units in 2 injection sites, preceded by 1gm of probenecid orally.

Duration upto 4 weeks.

Routes of Administration    Deep  I.M..

Contraindications

In patients hypersensitive to penicillin.

Precautions / Practice points

·    Administer only after test dose, to safeguard against anaphylactic reactions to penicillin.

·    Renal and haematological states to be monitored during prolonged and high dose therapy.

·    Administration Instructions:

-  Upper outer quadrant of gluteal region is preferred.

-  Never administer IV, SC or intra-arterially, since irritation and tissue necrosis occurs.

-  Do not dilute the solution.

Drug Interactions

Non fatal:

·    Probenecid prolongs half life on benzyl penicillin.

·    Bacteriostatic drugs decrease the efficacy reducing active bacillary multiplication (do not give other bacteriostatics along with the drug).

Adverse Effects

Common effects:

Pain at injection site.

Rare effects:

Hypersensitive reactions – anaphylactic shock – urticaria,edema, fever, eosinophilia, serum sickness like reactions chills, fever, edema, arthralgia, may occur in susceptible individuals. Treat with oxygen, epinephrine and IV steroids.

Drug Toxicity

Neuromuscular hyperirritability (agitiation, hallucination, tremors and fits can occur)

Symptomatic and supportive treatment.

Storage

Store at temperatue not exceeding 30oC in air tight containers.

Shelf   Life                     36 months.

AMOXYCILLIN

General   Information

Drug Code                        Preparation                                                Strength

         50                            Cap. Amoxycillin                                            250 mg.

       443                          Amoxycillin oral suspension                          125 mg/ml.

Description of the Drug

Amoxycillin is a sent synthetic penicillin a derivative of ampicillin.  It is bactericidal agent.  Like ampicillin it is orally effective, with the same spectrum of action.

Mode of Action

Amoxycillin interferes with the formation of peptidoglycan, necessary for bacterial cell wall synthesis.  It thereby causes defective cell wall formation and death of the bacteria.

Specturm of Action.

It is not effective against penicillinase producing Staphylococci.

Gram positive:

Streptococcus, Pneumocci, Non-penicillinase producing Staphylococci, Bacillus anthracis, Clostridium species, Corynebacterium species, Enterococci, Listeria.

Gram negative :

H.influenza, Neisseria gonorrhoea, Neisseria meningitidis, Proteus mirabilis, Salmonella, Shigella, E.coli.

Others :

            Actinomycetes.

Pharmacokinetics

Amoxycillin is resistant to inactivation by the gastric acid secretions.  It is rapidly and completely absorbed and has no relation to food. Plasma half  life is 1-3 hours necessitating a 3 or 4 times a day dosing schedule.  Most of the drug is excreted unchanged in the urine.

Clinical  Information

Indications

·    Respiratory tract infections sinusitis, bronchitis, otitismedia, caused by susceptible strains of H.influenza, Pneumococci.

·    GI infection – typhoid, paratyphoid fevers, gastroenteritis caused by Shigella, Enterococcoi etc.

·    Infective endocarditis caused by Streptococcus.

·    Urinary Tract infections by susceptible strains of E.coli, Enterobacter etc.

·    Uncomplicated gonococcal infections.

·    For elimination of H.pylori in acid peptic disease.

·    Prophylaxis of infective endocarditis before dental procedures, minor surgical procedures, invasive investigations.

·    Adjunct in treatement of Listerial meningitis.

Dosage

Usual dose in respiratory infections.

Adults  - 250-500 mg 8th hourly – maximum of 2-3 gm/day.

For uncomplicated gonorrhoea: single dose of 3 gam, preceded by 1 gm of probenecid.

Prophylaxis of endocarditis

3 gm of amoxycillin is given 1 hour before the procedure.

For H.plyori eradication : 250-500 mg 3 times a day, along with tetracycline, metronidazole or bismuth salicylate.

Children – Less than 40 kg – 20-25 mg/kg/day in divided doses.

      More than 40 kg – 250 mg 8th hourly.

Duration  - 10 – 15 days.

Routes of Administration      Oral.

Contraindications

·    Known allergy to penicillin.

·    Severe renal failure.

Precautions / Practice points

·    For streptococcal infection give for atleast 7-10 days.

·    Patients who are hypersensitive to penicillin may be hypersensitive to amoxycillin also.

·    Doses should be reduced in renal dysfunction (see appendix).

·    Periodic monitoring of renal, hepatic and haematologic function tests to be done in prolonged therapy.

·    Administraion Instructions:

-  May be taken with food.

Drug Interactions

Non fatal:

·    Probenecid inhibits the secretion of amoxycillin in the renal tubule and can be used to increase the levels and duration of action of amoxycillin.

·    Amoxycillin reduces the effectiveness of oral contraceptive pills.

Adverse Effects

Common effects:

·    GI side effects – nausea, vomiting and diarrhoea are caused by disruption of the normal balance of intestinal microorganisms (less common than with ampicillin).

·    Skin rash  - maculopapular rash (similar to ampicillin rash, but less common than in)especially in patients with inrections mononucleosis, HIV infection.

Rare effects :

·    Pseudo membranous colitis caused by superinfection with Clostridium difficile.

·    Vaginitis due to candidial overgrowth.

·    Nephrotoxicity  - interstitital nephritis may occur.

·    SGOT and SGPT elevations may occur.

Drug Toxicity

GIT  - abdominal pain, vomiting, diarrhoea.

CNS  - hyperactivity or agitation, hallucinations and tremor may be present.

Renal – may go in for intestitial nephritis and oliguric renal failure.

Treatment of Toxicity

·    Induce emesis, lavage if ingested.

·    Symptomatic therapy.

Storage

Syrup lasts for week, once opened.  Store at room temperature.

Shelf   Life

               Amoxycillin trihydrate capsules         -                   24    months

               Amoxycillin trihydrate capsules         -                   18    months

CHLORAMPHENICOL

General   Information

Drug Code               Preparation                                                Strength

       61               Chloramphenicol Palmitate oral suspension     - 125 mg/ml

      402              Chloramphenicol sodium succinate injection   - 250 mg/ml

       51               Capsule Chloramphenicol                                 - 250 mg.

Description of the Drug

It is a braod spectrum antibiotic obtained from streptomyces venezuelae.

Specturm of Action.

Gram positive:

Staphylococcus species, Streptococcus species, Pneumococci.

Gram negative :

Salmonella, Vibrio cholera, Neisseria, H. influenza, E.coli, Klebsiella, Proteus, Shigella, Campylobacter jejuni, Yersinia pestis etc.

Others :

            Bacteroides species, Rickettsia.

Mode of Action :

It is a bacteriostatic agent.  It inhibits bacterial protein synthesis by binding reversibly to 50 S subunit of bacterial ribosomes.

Pharmacokinetics

When given parenterally, chloramphenicol sodium succinate is split by esterases in the plasma to release active base. When given orally it is absorbed from the gut, as its active base, after being split from palmitate component by gut lipases.  It is widely distributed and penetrates the CNS and CSF well.  Half life is 6-8 hours.  Inactivated in liver mosly by conjugation and excreted in the urine both as unchanged drug (10%) and as metabolites (90%).

Clinical  Information

Indications

·    In typhoid fever  - as an alternative to quinolones or cephalosporins,  (in allergic individuals) or in severe typhoid infections caused by strains resistant to these two groups of drugs.

·    As an alternative to penicillin in meningitis caused by Neisseria meningitidis.

·    Alternative drug in infections caused by H. influenza such as, epiglottitis, respiratory infections, meningitis etc.

·    In severe infections like septicaemia and brain abcess etc.caused susceptible organisms when other drugs have failed.

·    Rickettsial infections.

Dosage

·    In Typhoid :

Adults : Oraz – 500 mg, 6 hourly (maximum 4 gm).

  IV  -  1 gm,  6 hourly (maximum 4 gm ) for 14-21 days.

Children : 50 mg/kg/day in 4 divideed doses  - 14-21 days.

·    In H. influenza pneumonia / meningitis:

Adult : 50 – 100 mg/kg/day – IV for 8-14 days.

Neonates – 25 mgm/kg/day in 6th hourly doses.

Children  - 50 mgm/kg/day in 6th hourly doses.

Duration  - 14-21 days.

Routes of Administration      Oral,   I.V.

Contraindications

·    History of hypersensitivity or bone marrow depression with the drug.

·    Pregnancy, lactation.

·    Hepatic failure.

·    Porphyria.

Precautions / Practice points

·    Baseline blood ovestigation to be done prior to treatment and monitored frequently, during the treatment period.

·    Does not need modifications in dose in case of renal failure since 90% of the drug is excreted as inactive metabolites.

·    Dose to be reduced in hepatic dysfunction

·    In neonates and  infants use only for cases of severe typhoid infection or meningitis.

·    Do not prescribe for trivial infections due to its systemic toxicity.

·    Avoid in pregnancy and lactation.

·    If given for more than a week, look for and treat superinfection with fungi like vaginal and oral candidiasis.

·    Avoid with other bone marrow depressants.

·    Administration Instructions:

-     Make up the injection with water or 5% dextrose.

-     Maximum concentration not exceeding 100 mg/ml i.e use at least 3-5 ml to make up solution.

-     Inject very slowly over 3-5 min.

Drug Interactions:

Potentially fatal:

·    Enhances the effects of sulphonylureas and increases risk of hypoglycemic episodes.

·    Enhances the effects of oral anticagulants and risk of bleeding.

Non fatal:

·    Increases the serum levels of phenytoin.

·    Being a bacteriostatic, can reduce efficacy of bactericidals like penicillins by inhibiting bacterial multiplication.

·    Phenobarbitone, rifampicin and other enzyme inducers increase clearance of chloramphenicol.

Adverse Effects

Common effects:

·    Nausea, vomiting and diarrhoea in 2-5 days of therapy due to alteration of gut microbial flora.  Vaginal candidiasis may also occur.

·    Bone marrow suppression.  At doses more than 50 mg/kg/day, may cause maturation arrest in RBC, causing anemia and reticulocytopenia.  It is reversible if the drug is withdrawn, leucopenia and agranlocytosis can also occur.

Rare effects :

·    Aplastic anemia is a genetically determined idiosyncrasy of the particular individual and is irreversible and not dose dependent.

·    Headache, mental confusion, delirium.

·    Anaphylaxis and hypersensitivity reaction like skin rashes, urticaria and angioedema.

In neonates :

·    Grey baby syndrome (vasomotor collapse in neonates following doses more than 75 mgm/kg/day) – ashen grey skin, low body temperature,vomiting, irregular and rapid respiration, lethargy and flaccidity.

Drug Toxicity

Symptoms are anemia, metabolic acidosis, hypotension and hypothermia.

Treatment of Toxicity

·    Gastric lavage and emesis.

·    Supportive therapy.

Storage

·    Keep below 30o C, protect from light.

·    Once dissolved for parenteral use the solution must be clear and used within 24 hours.

·    Once opened the syrup should be kept cool and used within one week.

Shelf   Life

            Chloramphenicol Palmitate oral suspenision   - 24  months.

Chloramphenicol sodium succinate injection   - 36 months.

Capsule Chloramphenicol                                  - 24 months.

DOXYCYCLINE

General   Information

Drug Code                        Preparation                                                Strength

       53                         Cap. Doxycycline                                             - 100 mg.

Description of the Drug

Doxycycline is a broad spectrum antibacterial agent belonging to the tetracycline group of drugs.

Mode of Action

Doxycycline inhibits bacterial protein synthesis by binding to the 30s subunit of the bacterial ribosome.  It is  a bacteriostatic agent.

Specturm of Action.

Gram negative bacteria :

V. Cholera, E.coli, Klebsiella, Enterobacter, Shigella, Bacteroides, Neisseria gonorrhoea, Calymmatobacterium granulomatis.  H. ducreyi, H. influenza, Yersinia pestis, Moraxella species, Brucella species.

Gram positive bacteria :

Streptococcus pyogenes, Streptococcus faecalis, Pneumococcus, alpha hemolytic streptococcus.

Others :

Chlamydia, Mycoplasma, Ureaplasma, Borrelia species, Treponema, Clostridia, B. anthracis, Rickettsiae, Entamoeba coli, Balantidium coli, Plasmodium falciparum, Actinomycetes.

Pharmacokinetics

It is readily and completely absorbed from the GIT 80-95% is bound to plasma proteins.  Biological half-life is 15-25 hours, excreted in the urine and rest in the bile.  Not metabolized in the liver.

Clinical  Information

Indications

·    In the treatment and prophylaxis of cholera.

·    Treatment of plague.

·    Respiratory infections caused by mycoplasma, ureaplasma and mixed bacterial infections; Chronic bronchitis caused by H.influenza.

·    Chlamydial infections – Trachoma, Psittacosis, Salphingitis, Urethritis and Lymphogranuloma venereum.

·    Adjunct to treatment of pelvic inflammatory disease.

·    Non gonococcal urethritis caused by ureaplasma.

·    Alternative drug in leptospirosis.

·    Prophylaxis in P. falciparum malaria.

·    Infections cuased by borrelia species – Lyme’s disese, relapsing fever.

·    Brucellosis.

·    Granuloma inguinale.

·    Rickettisal infections like rocky mountain spotted fever, typhus fever, Rickettsial pox, tick fever.

·    Chancroid.

·    Acne.

Dosage

Use dose is 200 mg of doxycycline on the first day (100 mg b.d) followed by 100 mg daily.

·    For gonorrhoea and chlamydial genito urinary infection –100 mg b.d for 7-21 days.

·    Malaria prophylaxis – 100 mg daily for 1-2 days before going to endemic area and continued for four weeks after.

Duration upto 21 days.

Route of Administration      Oral.

Contraindications

·    Pregnant women.

·    Lactating mothers.

·    Children below 8 years.

Precautions / Practice points

·    Can be given safely in renal failure.

·    Avoid in prophyria patients.

·    Instruct patients  to avoid sunlight (risk of photosensitisation).

·    Administration Insturctions:

-  Doxycycline  capsules or tablets should be given with plenty of fluids, and with the patient in an upright position.

-  Do not administer with milk, other calcium containing food, antacids, bismuth or iron containing substances.

Drug Interactions:

Potentially fatal:

·    Doxycycline increases plasma cyclosporin levels and may precipitate toxicity.

Non fatal:

·    The drug’s metabolism may be increased by agents that induce hepatic metabolism such as barbiturates, phenytoin, rifampicin, carbamazepine, theraby reducing efficacy of doxycycline.

·    Antacids with calcium, magnesium, bismuth causes decrease in the absorption of doxcycyline.

·    Not to be given with bactericidal drugs like penicillin, since it decreases bacterial multiplication and hence reduced efficacy of the bacteriocidal agent except diseases like Brucellosis and Leptospirosis.

·    Decreases efficacy of oral anticoagulants.

Adverse Effects

Common effects:

·    Nausea, vomiting, epigastric distress, oesophageal ulceration.

·    Superinfection with nonsusceptible organisms – pseudomembranous colitis and vaginal candidiasis can occur.

·    Deposition of the drug in bone and teeth in growing children, causing discolouration and hypoplasia of the teeth and stunting of growth.

Rare effects :

·    Photosensitization – skin rashes, maculo popular and erythematous rashes.

·    Nephrotoxicity – interstitial nephritis can occur.

·    Hypersensitivity reaction – urticaria, angioneurotic edema, serum sickness like reactions.

·    Benign intracranial hypertension may develop, causing headache and visual disturbances.

Drug Toxicity

Symptoms of overdose are – nausea, vomiting, diarrhoea, hypersensitivity reactions.

Treatment of Toxicity

Supportive and symptomatic, maintain hydration and electrolyte balance.

Storage

·    Keep in a cool dry place.  Protect from light.

Shelf   Life                   2 years.

ERYTHROMYCIN

General   Information

Drug Code                        Preparation                                                Strength

       55                          Tab. Erythromycin                                             250 mg.

       62                          Erythromycin oral suspension                           125 mg/ 5 ml.

Description of the Drug

Erythromycin is a macrolide antibiotic produced by streptomyces erythreus with a primary bacteriostatic action.

Mode of Action

Erythromycin acts by inhibiting bacterial protein synthesis by binding reversibly to the 50’s subunit of the ribosome.

Specturm of Action.

Gram positive organisms – Streptococcus, Staphlococcus, Pneumococcus, 

               Corynebacterium, Listeria, Clostridia.

Gram negative organisms  - Bordetella, Neisseria, Campylobacterjejuni.

Others – Chlamydia, Mycoplasma, Ureaplasma, Treponema, H. ducreyi,

Helicobacter,  pylori, Mycobacterium avium intracellulare, Legionella, Actinomycetes.

Pharmacokinetics

Absorbed well from GIT but food reduces absorption, and may be destroyed by acid.  It is widely distributed throughout body tissues.  Mainly excreted in the bile and undergoes enterohepatic circulation some drug is excreted unchanged in the urine.

Clinical  Information

Indications

As an alternative to penicillin in the treatment of :

·    Respiratory infections – sinusitis, bronchitis, pneumonia and lower respiratory infections caused by  Streptococci/ Staphylococci and Pneumococci.

·    Skin and soft tissue infections by Staphylococcus aureus.

·    Gonococcal infections and syphilis.

·    Prophylaxis of infective endocarditis and in rheumatic fever.

Drug of choice in :

·    Pertussis – the disease as well as eradication of carrier state.

·    Legionnaires disease.

·    Campylobacter jejuni enteritis.

·    Chlamydial infection  - Trachoma, LGV, Psittacosis, Nongonococcal urethritis.

Dosage

Usual dose

Adults : 250 – 500 mg 6th hourly.

Children : Oral dose   30-40 mg/kg/day in 4 divided doses.

·    For IE prophylaxis – 1 gm, 1 hour before procedure and 500 mg q.i.d for 2 days afte procedure.

·    For rheumatic fever prophylaxis – 250 mg b.d.  – continous prophylaxis.

·    For chlamydiae urogenital infection  - 500 mg q.i.d. for 7 – 14 days.

Treatment of  syphilis  - 500 mg, q.i.d. for 14-21 days.

Route of Administration      Oral.

Contraindications

·    Acute porphria.

·    Hypersensitivity to macrolides.

·    Hepatic failure.

·    Patients on terfenadine, astemizole.

Precautions / Practice points

·    Use with caution in liver disease since it is primarily excreted by liver.  Montor SGOT and SGPT periodically.  Instruct patients to report immediately if signs of hepatotoxicity occur – jaundice, anorexia, nausea, right hypochondrial pain etc.

·    With caution in pregnancy, lactation.

·    Observe patient for superinfection and treat immediately.

·    Administration Instructions:

-  Give 1 hour before food in the fasting state for better absorption.

Drug Interactions:

Potentially fatal:

·    It increases serum levels and toxicity of theophylline.

·    Enhances effects of oral anticoagulants.

·    Patients on terfenadine, astemizole disopyramide and cisapride – erythromycin alters metabolism of these drugs and causes serious cardiovascular adverse effects – QT prolongation, ventricular arrhythmias and even cardiac arrest.

Non fatal:

·    Inhibits metabolism of carbamazepine, valproate and increases their serum levels.

·    May enhance the effects of benzodiazepines, digoxin, cyclosporin, bromocriptine.

Adverse Effects

Common effects:

·    GIT  - abdominal disconfort, nausea, vomiting, diarrhoea.

Rare effects:

·    Pseudomembranous colitis, superinfection with fungi.

·    Liver – Cholestatic Jaundice and hepatotoxicity, probably as an idiopathic hypersensitivity reaction.

·    Hypersensitivity – Pruritus, urticaria, skin rash and rarely anaphylaxis.

·    Vertigo and reversible hearing loss.

·    Heart  - Prolongation of QT interval, arrhythmias, tachycardia, palpitation and chest pain.

Drug Toxicity

Nausea, vomiting and diarrhoea may occur.

Treatment of Toxicity

General supportive care.

Storage

Store in airtight containers.  Temperature not to exceed 30 C. Protect from Light.

Shelf   Life

Erythromycin stearate oral suspension   - 18 months

Erythromycin stearate Tab  - 3 years.

NORFLOXACIN

General   Information

Drug Code                        Preparation                                                Strength

       57                               Norfloxacin                                                 400 mg

Description of the Drug

Norfloxacin is a fluoroquinolone antibacterial agent.

Spetrum of action :

Gram positive aerobes:

Staphylococcus aureus, Streptococcus, Enterococcus faecalis.

Gram negative aerobes :

E.coli, Klebsiella, Proteus, Neisseria species, H.influenza, Enterobacter, Pseudomonas, Ureaplasma, Salmonella, Shigella, Vibrio species, Citro bacter, Yersinia, campylobacter species.

Mode of Action

It is a  bactericidal agent. It acts by inhibiting the replication of bacterial DNA by interfering with action of DNA gyrase during bacterial growth and reproduction.

Pharmacokinetics

Only 35-70% of oral norfloxacin is absorbed. The plasma half life is 6 hours (but as twice daily dosage schedule is adequate).  The drug is partially metabolized by the liver and is excreted by the kidney (as well as in the faeces).

Clinical  Information

Indications

·    Uncomplicated urinary tract infection – due to E.coli, Klebsiella and other susceptible bacteria.

·    Urethritis or cervicitis due to Neisseria gonorrhoea.

·    Bacterial prostatitis due to E.coli.

Dosage

Urinary tract infections – 400 mg twice daily for 3-21 days, depending on severity of infection.

Gonorrhoea  - single oral dose of 800 mg.

Prostatitis 400 mg twice daily for 28 days.

Duration  - 4 weeks.

Route of Administration      Oral.

Contraindications

            History of hypersensitivity.

Precautions / Practice points

·    Avoid use in pregnancy, lactating mothers, children and adolescents less than 18 years
because fluorouinolones produce erosionof immature cartilage.

·    Should be used with caution in patients with epilepsy or a history of CNS disorders.  (Can cause increased intracranial tension and may precipitate convulsions).

·    An adequate fluid intake should be maintained during treatment because of the risk of crystalluria.

·    Do not drive or operate machinery as norfloxacin may impair performance of skilled tasks.  Also abstain from alcohol as its CNS effects are enhanced by alcohol.

·    Administrative Instructions:

-     Take one hour before meals, with plenty of water.

-     Do not administer with antacids.

Drug Interactions:

Potentially fatal:

·    Norfloxacin decreases the clearance of theophylline and caffeine.  Seizures can occur if norfloxacin and theophylline are given concomitantly.

·    Effects or oral anticoagulants may be enhanced.

·    Increases serum levels of cyclosporins and its nephrotoxicity.

Non fatal :

·    Urinary excretion or norfloxacin is reduced by the concomitant administration of probenecid.

·    The absorption of norfloxacin is reduced by antacids containing aluminium or magnesium.  Dairy products with high calcium content, Zinc and iron Preparations and sucralfate.

·    Nitrofurantoin should not be concomitantly used, because it may antagonize the action of norfloxacin in the urinary tract.

Adverse Effects

Common effects:

·    Gastro-intestinal disturbances like nausea, vomiting, diarrhoea, abdominal pain.

Rare effects:

·    Pseudomembranous colitis and superinfection with fungi may occur .

·    CNS effects like headache, drowsiness, insomnia, tremors, dizziness, restlessness, confusion and rarely convulsions due to increased intracranial tension.

·    Rashes, pruritis, hypersensitivity type reactions including photosensitivity may occur.

·    Crystalluria if urine is alkaline.

Drug Toxicity

Signs of CNS stimulation, acute renal failure and seizures may occur.

Treatment of Toxicity

·    If acute, emesis and gastric lavage for GI decontamination.

·    Symptomatic treatment.

Storage

Keep in a cool dry place.  Protect from light.

Shelf   Life             3 years.

PHENOXYMETHYL PENICILLIN POTASSIUM

General   Information

Drug Code                        Preparation                                                          Strength

       437                          Tab. Phenoxymethyl Penicillin Potassium                125 mg

        58                           Tab. Phenoxymethyl Penicillin Potassium                 250 mg

Description of the Drug

Phenoxymethyl penicillin is a salt of penicillin which is acid-stable and can be given by mouth.

Mode of Action

It is a  bactericidal agent which binds to penicillin binding proteins in the organisms and interferes with synthesis of cell wall mucopeptide peptidoglycan, rendering the bacterial cell wall unstable and thereby killing the cell.

Spectrum of action :

Staphylococci (which do not produce penicillinase), Streptococci, Pneumococci, Neisseria gonorrhoea, N. Meningitidis, Corynebacterium,  B. anthracis, Clostridia, Actinomycetes, Listeria, Leptospirochaetes, Treponema, Enterococcus species.

Pharmacokinetics

Phenoxymethyl penicillin is absorbed well from the gastro intestinal  tract. Plasma half-life is about 30-60 minutes.  Some drug is metabolized in the liver, but mostly excreted unchanged in the urine.

Clinical  Information

Indications

In treatment of mild to moderately severe infections due to organisms susceptible to benzyl penicillin.

·    Mild to moderate infections of the upper respiratory tract caused by suscetible organisms like streptococci, pneumococci – pharyngitis, sinusitis, otitis media etc.

·    Other streptococcal infections like erysipelas, streptococcal tonsillitis etc.

·    Vincent’s angina – fusospirochaetosis of oropharynx.

·    Prophylaxis for :

-     Prevention of recurrence of rheumatic fever.

-     I.E prophylaxis in patients with – prosthetic heart valves, prior to minor surgeries etc.

-     Prevention of pneumococcal infection in patients with asplenia, sickle cell disease.

Dosage

Note : 250 mg is approximately equivalent to 4,00,000 units of benzyl penicillin.

·    Streptococcol and pnemococcal infections of respiratory tract.

·    Adult – 250 mg 6 hourly for 10 days.

·    Children – less than 1 year = 62.5 mg 6th hourly for 10 days.

1-5 Years = 125 mg 6th hourly for 10 days.

6-12     Years = 250 mg 6th hourly for 10 days.

·    Fusospirochaetosis.

250-500           Mg 6 hourly.

·    For I.E prophylaxis

2Gm, 1 hour before procedure and then 1 gm 6 hours later (halve the dosages for children below 30 kg).

·    For rheumatic fever prophylaxis – 250-500 mg b.d. continuously upto 35 years of age.

Duration – minimum 10 days.

Route of Administration      Oral.

Contraindications

            Known hypersensitivity.

Precautions / Practice points

·    Doses must be reduced in severe renal impairment (see appendix).

·    Periodic renal and hematologic function tests when on long term therapy.

·    On long term therapy (rhematic fever prophylaxis) monitor compliance.

·    Administration Instructions:

-  Administer on empty stomach one hour before meals.

Drug Interactions:

Non fatal :

·    With bacteriostatic agents, efficacy is reduced due to inhibition of active bacterial multiplication.

·    Probenecid increases plasma levels by interfering with excretion.

·    With potassium sparing diuretics, risk of hyperkalemia is more when large doses are given.

Adverse Effects

Common effects:

·    GIT – Nausea, vomiting, epigastric distress and diarrhoea.

Rare effects:

·    Superinfection with candida and other non susceptible organisms.

·    Hypersensitivity – rashes, fever, urticaria, serum sickenss like reactions may occur.

Drug Toxicity

Toxicity may be caused by the large quantities of potassium that accompany  penicillin

hyperkalemia may occur. Other manifestation of penicillin overdose – neural hyperirritability, tremor, agitation, confusion, or fits may occur.

Treatment of Toxicity

Continous monitoring of serum electrolytes and appropriate corrective measures.

Storage

Store in a cool, dark, dry place.

Shelf   Life             1 years.

AMIKACIN

General   Information

Drug Code                       Preparation                                                        Strength

        224                          Inj. Amikacin Sulphate                                        100 mg/ Vial

Description of the Drug

Amikacin is a semisynthetic – bactericidal agent, belonging to the aminoglycoside group of antibiotics.

Mode of Action

It interferes with bacterial protein synthesis, by binding irreversibly to the 30s subunit of the bacterial ribosomes.

Specturm of actions:

Mainly gram negative organisms:

Pseudomonas, E.coli, Proteus, Klebsiella, Providercia, Enterobacter, Yersinia pestis etc.

Moderately susceptible organisms:

Streptococcus pyogenes, Pheumococcus, Listeria and Staphylococcus aureus.

Pharmacokinetics

It is rapidly absorbed after intramuscular injection.  Peakplasma concentrations are achieved one hour after administration.  Plasma half-life is 2-3 hours.  CSF penetration is poor.  Excreted mostly unchanged by glomerular filtration in the urine.

Clinical  Information

Indications

·    Mainly used in treatment of gram negative infections resistant to gentamicin.

·    Treatment of  infections due to Pseumdomonas, Klebsella, E.coli such as septicemia, intra abdominal infection and peritonitis, infective endocarditis, complicated urinary tract infections.

·    Prophylaxis in burns and post operative situations.

·    CNS  - meningitis caused by susceptible organisms, along with a beta lactam antibiotic.

Dosage

Adults and Children

15 mg/kg/day in 3 divided doses in equal 8th hourly intervals.

Neonate : Loading dose of 10 mg/kg followed by 7.5 mg/kg 12 hourly.

Duration  - 7-10 days.

Routes of Administration     I.M.,    I.V.

Contraindications

·    Renal failure.

·    Pregnancy.

·    Hearing and vestibular problems.

·    Myasthenia gravis.

Precautions / Practice points

·    Treatment should not continue for longer than 7-10 days due to risk of nephrotoxicity and neurotoxicity.

·    It given in combination with a beta lactam antibiotic – efficacy is improved.

·    Monitor nephrotoxicity while patient is on therapy by periodic urine examination.  It is manifested by decrease in specific gravity, increase in proteins, presence of cells or casts, reduced creatinine clearance and increased blood urea nitrogen.  Nephrotoxicity is minimized by proper hydration and adequate urinary output.

·    Ask patient to report immediately if tinnitus or vertigo occurs and stop the drug.  Monitor vestibular and cochler function tests if given for more than 7 days.

·    Very high doses of amikacin experimentally has caused neuromuscular block and respiratory paralysis.  Hence, caution with patients on anaesthesia and neuromuscular blocking agents like d-tubocurarine etc.  Intravenous calcium gluconate may be used for treatment of neuromuscular blockade.

·    Dose adjustments to be made in renal dysfunction – divide the dose to be given, by serum creatinine level;  If serum creatinine level is 2 mg – only 50% of dose to be given (see appendix.

·    Administration Instructions:

-   Give IV injections slowly (over 3-5 min)

-   Do not mix with other drugs like penicillins, due to physical incompatibility.

-   Intravenous infusions can be given in 5% dextrose or normal saline.

Drug Interactions:

Potentially fatal :

·    Drugs which increase nephrotoxicity of amikacin.

-  Cephalosporins.

-  Amphotercin B.

-  Other aminoglycosides.

-  Cisplatin, vancomycin etc.

-  Cyclosporin.

·    Amikacin can potentiate neuromuscular blockade of skeletal muscle relaxants like d-tubocurarine.

Non fatal :

·    Ototoxicity of amikacin is  increased by diuretics like frusemide and ethacrynic acid.

·    Indomethacin increases plasma levels of amikacin.

·    Effects of nondepolarising muscle relaxants are enhanced.

Adverse Effects

Dose and duration dependent.

·    Ototoxicity – Both vestibular & cochlear.

·    Headache, dizziness, vertigo, ataxia, hearing loss, tinnintus.

·    Other manifestations of neurotoxicity – numbness, twitching of muscle, paraesthesias.

·    Nephrotoxicity – reversible on withdrawl of drug.

·    Acute tubular necrosis, intestitial nephritis may occur.

·    Neuromusular blockade – curare like effect, resulting in paralysis. Respiratory paralysis and apnoea may occur.

·   

Drug Toxicity

·    Signs of eight nerve dysfunction – tinnitus, vertigo.

·    Neurotoxicity – Encephalopathy, confusion, lethargy, hallucination, convulsions, mental depression.

Treatment of Toxicity

·    Adequate hydration to maintain good urine output of 3ml/kg/hour.

·    Haemodialysis or peritoneal dialysis, symptomatic treatment.

Storage                    Store in airtight containers.

Shelf   Life             2 years.

CEPHALEXINE

General   Information

Drug Code                        Preparation                                                          Strength

        229                          Cap. Cephalexine                                                      250 mg

        445                          Cephalexine Oral Suspension                                   125 mg/5 ml

Description of the Drug

Cephalexine is a semi synthetic first generation cephalosporin antibiotic.

Mode of Action

It is a bactericidal agent.  Cephalexine interferes with the synthesis of peptidoglycan and bacterial cell wall synthesis.  It also activates autolytic enzymes within the cell.

Specturm of actions:

Mainly gram negative organisms:

Staphylococcus aureus, Pneumococcus, Streptococcus viridans, group  A hemolytic streptococci, Streptococcus pyogenes, Clostridium perfringens, Fusobacteria.

Some gram neagative organisms:

E.coli, Klebsiella, Proteus, H.influenza.

Pharmacokinetics

Almost completely absorbed from gastro-intestinal tract not inactivated by acid.  Plasma half life is 4-6 hours.  It is not metabolized and about 80% is excreted unchanged in the urine.  No  CNS penetration occurs.

Clinical  Information

Indications

·    Respiratory tract infections and otitis media by susceptible organisms such as Streptococcus pneumoniae, H. influenza, Streptococcus pygenes especially in patients allergic to penicillin.

·    Skin infection by susceptible strains of streptococcus and staphylococcus.

·    Bone and joint infection by staphylococcus aureus.

·    Genito urinary tract infections, prostatitis by E.coli. Proteus, K.pneumoniae.

Dosage

Adults      250-500 mg 6 hourly, upto a maximum of 4 gm/day.

For urinary tract infections  - 7-14 days:

For Streptooccus  pharyngitis, skin infections : 500 mg 12th hourly.

Children  25-50 mg/kg/day in divided doses every 6 hours; upto a maximum of 3gm/day.

Duration   - 10 days.

Route of Administration     Oral.

Contraindications

Known allergy to cephalosporins andpenicillins.

Precautions / Practice points

·    Cross sensitivity to penicillin may be present. Hence in a patient suspected to be allergic to penicillin, administer cephalexine only after skin testing is done.

·    Reduction in renal impairment is advised (see appendix).

·    False positive coomb’s test may occur, false positives may also occur in testing of reducing sugars in the urine (Benedicts) and in urinary proteins and steroids.

·    Look for and treat superinfection with nonsusceptible organisms such as mucocutaneous candidiasis, diarrhoea etc.

·    With prolonged therapy monitor renal, hepatic and haematalogical tests.

·    Adminstration Instructions:

-     Administer one hour before meals to facilitate absorption.

Drug Interactions:

Non fatal :

·    Probenecid decreases renal excretion.

·    Aminoglycosides may increase nephrotoxicity.

·    May interfere with efficacy or oral contraceptives.

Adverse Effects

Generally well tolerated:

Common effects:

·    Gastro intestinal disturbances (due to alteration of normal bacterial floral) such as abdominal pain, diarrhoea can occur.

Rare effects:

·    Superinfection with fungi and pseudomembranous colitis can occur.

·    Hypersensitivity reactions including skin rashes, urticaria, angioedema, eosinophilia, fever reactions resembling serum sickness and anaphylaxis.

·    Elevation of liver enzymes – SGOT and SGPT, cholestatic jaundice or hepatitis.

·    Nephrotoxicity – elevation of blood urea nitrogen, creatinine and interstitial nephritis.

Drug Toxicity

·    Nausea, vomiting, epigastric distress, diarrhoea, haematuria, neuromuscular irritability and seizures may occur.

Treatment of Toxicity

·    If acute – gastric lavage, activated charcoal to decrease the absorption, monitor vital signs and electrolytes.

·    Symptomatic treatment.

Storage

             Store in a cool, dry, dark place.

Shelf   Life             2 years.

NITROFURAZONE

General   Information

Drug Code                      Preparation                                               Strength

        417                          Nitrofurazone                                            0.2% w/w  - ointment

Description of the Drug

Nitrofurazone is a nitrofuran derivative, used as a topical antibacterial agent.

Mode of Action

It acts by inhibiting enzyme necessary for carbohydrate metabolism in bacteria.

Specturm of actions:

·    Staphylococcus species, Streptococcus species, E.coli, Enterobacter, Clostridium species, Aerobacter.

·    Not effective against Pseudomonas, fungi or viruses.

Pharmacokinetics

It is applied topically.  Systemic absorption does not occur.

Clinical  Information

Indications

·    As an antibacterial in second and third degree burns.

·    Local application for wounds, ulcers and skin infections.

·    In surgical dressings, for skin grafting.

Dosage

Topically applied once daily or as necessary, during dressing changes.

Routes of Administration     Topical

Contraindications

Patients with known hypersensitivity.

Precautions / Practice points

·    Loses its potency in presence of organic matter like pus and serum and alkaline solutions.

·    Discontinue immediately if itching or irritation develops at site of application – may indicate hypersensitivity.

Adverse Effects

·    Sensitization and allergic skin reactions like urticaria, skin rashes, exfoliative dermatitis etc may be produced by the topical application of nitrofurazone.

·    Generalized allergic reactions – allergic pneumonitis can occur.

Storage

             Store at a temperature not exceeding 40o C in airtight containers.

Shelf   Life             2 years.

6.2.1                       Anti   tuberculosis

Inj.  STREPTOMYCIN

General   Information

Drug Code                        Preparation                                               Strength

        127                          Inj.  Streptomycin                                  750mg 5 ml vial

Description of the Drug

Streptomycin is a aminoglycoside antibiotic which is particularly active against M. tuberculosis as well as many Gram-negative bacteria.

Mode of Action

Inhibits bacterial protein synthesis by binding irreversibly to the 30s subunit of the ribosome.

Specturm of actions:  M. tuberculosis.

Others :

E.coli, Proteus, Klebsiella, Enterococcus, Streptococcus viridans, Yersinia pestis, H.influenza, H.ducreyi, Calymmatobacterium granulomatis, Brucella.

Pharmacokinetics

It is not absorbed orally, hence must be administered only parenterally (I.M.) Serum levels of streptomycin declines 6-7 hours after administration.  The drug is excreted in the urine, mainly unchanged.

Clinical  Information

Indications

Tuberculosis:

Alternative drug in the treatment of TB, when other drugs in the regimen are either ineffective due to resistance or is contraindicated due to toxicity or intolerance.

Non Tuberculous Indications:

Alternative drug in treatment of

·    Granuloma inguinale.

·    Chancroid due to H. ducreyi.

·    Gram negative septicaemia.

Other infections by susceptible organisms

·    Plague.

·    Tularemia.

·    Brucellosis.

Dosage

In treatment of Tuberculosis, twice wekly regimen for 6-9 months

Children  - 25-50 mg/kg biweekly.

Adults     - 20-40 mg/kg – maximum 1 gram biweekly.

In treatment of plague/tularemia – 1-2 gram in divided doses for 7-14 days not to exceed 2 gram/day.

Routes of Administration     I.M.

Contraindications

·    Renal failure.

·    Hypersensitivity to streptomycin or other aminoglycosides.

·    Pregnancy and infants  - crosses the placental barrier and effects is ototoxic to the fetus.

Precautions / Practice points

·    Monitor nephrotoxicity while patient is on treatment, by periodic urine examination, manifested by decrease in specific gracity, increase in proteins, presence of cells or casts, reduced creatinine clearance and increased blood urea nitrogen.  Nephrotoxicity is decreased by proper hydration and ensuring adequate urinary output.

·    The course of treatment should be limited to 7-10 days other than in treatment of tuberculosis.

·    Dosage should be adjusted according to factors such as age, duration of treatment, renal impairments or high dose may predispose to toxicity.

·    Warn patient to report immediately if tinnitus, noises or a sense of fullness in the ears is felt; if detected early enough and the drug is stopped, ototoxicity is reversible.

·    Superinfection with nonsusceptible organisms such as candida may occur hence they should be looked for an treated.

·    Administration Instructions :

-     Administer as deep I.M. injection.

Drug Interactions:

Potentially fatal:

·    Cytototoxic drugs, vancomycin and cyclosporin enchance nephrotoxicity.

·    Non depolarizing muscle blockade in enchanced  - respiratory paralysis may ccur and recovery is prolonged.

Non fatal:

·    Ototoxic effects of streptomycin are increased by diuretics like frusemide, ethacrynic acid.

Adverse Effects

They are dose and duration depedent.V

·    Vestibular toxicity manifestations  - nausea, vomiting and vertigo.

·    Paraesthesia in and around the mouth.

·    Neurological symptoms including peripheral neuropathies optic neuritis and scotoma.

·    Hypersensitivity reactions  - rashes, urticaria, angioneurotic edema and eosinophilia.

·    Nephrotoxicity is rare with streptomycin when compared to other aminoglycosides.  Still risk of renal toxic effects like –interstitial nephritis, acute tubular necrosis may occur.

Drug Toxicity

            Ototoxicity, optic nerve dysfunction, nephrotoxicity may occur.

Treatment of Toxicity

·    Adequare hydration and diuresis, heamo or peritoneal dialyasis.

·    Symptomatic and supportive treatment.

Storage

             Keep in a cool dry place.

Shelf   Life             2 years.

RIFAMPICIN

General   Information

Drug Code                              Preparation                                       Strength

    247                                      Cap. Rifampicin                                   450 mg

    128                                      Cap. Rifampicin                                   150 mg

    453                                      Rifampicin (oral                     100 mg/5ml

                                                Suspension)

Description of the Drug

Rifampicin is an antibiotic produced by streptomyces mediterrans.

Spectrum of action :

·    Mycobacteria – M : Tuberculosis and M. leprae.

·    Some gram positive organisms : Staphylococcus aureus, Staphylococcus epidermidis.

·    Gram negative cocci : Neisseria menigitidis, Neisseria gonorrhoea.

·    Others H. influenza, Chlamydia, Legionella and some viruses.

Mode of  Action

It acts by binding to DNA dependent RNA  polymerase and blocks RNA synthesis in the organisms. It is a bactericidal agent, capable of killing intracellular  organisms and dormant bacilli.

Pharmacokinetics

It is  readily absorbed from the GIT. Absorption is decreased by food, Secreted in the bile, undergoes enterohepatic recirculation  and excreted mainly unchanged in faeces and some amount in the urine.

Clinical  Information

Indications

·    In treatement of Tuberculosis in combination with isoniazid, ethambutol and pyrazinamide as a component of multi drug regimen.

·    Along with dapsone and clofazimine in treatment of leprosy.

·    To eliminate meningococcal carrier state in asymptomatic infection.

Dosage

Adult

·    600 mg/day – o.d. – for 6 – 9 months in antituberculosis regimens.

·    For M.leprae – 600 mg/month for 6 month to 1 year in multidrug theraphy  of leprosy.

Children

·    10 mg/kg body weight orally.

            Duration – depends upon the disease ( 3 – 6 months).

Route of Administration     Oral.

Contraindications

·    Preexisting liver disorders, Jaundice.

·    Thrombocytopenia.

·    Known hypersensitivity to the drug.

·    Porphyria.

Precaution / Practice points

·    Assess patients blood counts and liver function tests prior to theraphy and monitor at  periodic intervals ( 2 –4 weeks) SGOT and SGPT levels. Ask patient to report immediately if symptoms of anorexia, nausea, malaise, jaundice occurs.

·    Instruct patients that orange discolourisation of sweat, urine and tears is harmless.

·    Drug should be withdrawn, if thrombocytopenia occurs.

·    Administration Instructions :

-   To be administered one hour before meals, first thing in the morning.

Drug Interactions

Potentially fatal :

Rifampicin reduces the therapeutic efficiency of drug like

·    Antiarrhythmics : Verapamil, disopyramide, quinidine.

·    Theophylline.

·    Thyroxine.

·    Oral hypoglycemics – chlorpropamide, tolbutamide which may have hazardous consequences.

Non fatal :

·    Rifampicin induces hepatic cytochrome P450 enzyme pathways thereby reducing the efficacy of – oral contraceptives, oral anticoagulants, antifungals (Ketoconazole), steroids, phenytoin, carbamazepine, nifedipine, diazepam, cipropfloxacin, dapsone, chloramphenicol, haloperidol, enalapril.

·    Hepatotoxicity of rifampicin  is increased when administered with isoniazid and halothane.

·    Antacids reduce absorption of rifampicin.

·    Cotrimaxazole and probenecid may increase rifampicin levels

Adverse Effects

Common effects :

·    Elevation of SGOT and SGPT may occur : It does not warrant stopping the drug, but hepatotoxicity reactions and hepatitis with hepatocellular damage needs cessation of  therapy.

·    Flu like syndrome – feve, chills, malaise.

·    Haemopoietic – thrombocytopenia, causing purpura. It is reversible effect. The drug should be withdrawn on the appearance of purpura.

·    Orange discolourisation of sweat, urine, tears. Rashes and itching may occur.

·    GIT – anorexia, nausea, vomiting, epigastric distress, cramps, diarrhoea.

Rare effects :

·    Nephrotoxicity, interstitial nephritis and kidney failure may occur.

·    Pseudomembranous colitis may also occur.

·    CNS – headache, ataxia, dizziness, confusion.

·    Hypersensitivity to the drug like anaphylactic reactions.

Drug Toxicity

·    Nausea, vomiting, lethargy, brownish discolouration of skin, urine sweat, saliva, CNS depression and tender hepatomegaly, hepatic necrosis and failure may occur.

Treatment of Toxicity

·    Gastric lavage, activated charcoal to prevent absorption of poison.

·    Antiemetics for nausea.

·    Active diuresis and hemodialysis may help remove the absorbed poison.

·    Symptomatic therapy.

Storage

·    Store in airtight containers, at a temperature not exceeding 15o C in an atmosphere of nitrogen.

·    Protect from light.

Shelf Life                 2 years.

ISONIAZID (INH)

General  Information

Drug Code                              Preparation                             Strength

    130                                      Tab. INH                                 100 mg

    131                                      Tab. INH                                 300 mg

Description of the Drug

Isoniazid, the hydrazide of isonicotinic acid is a structural analogue of pyridoxine.

Mode of Action

It is a bactericidal agent for actively growing tuberclbacilli. The primary action of INH is to inhibit the biosynthesis of mycolic acid, a constituent of the mycobacterial cell wall. It acts on both intracellular and extracellular organisms.

Pharmacokinetics

Isoniazid is readily absorbed from the GIT . Diffuses into all body fluids, cells and caseous material, crosses the blood brain barrier and the CSF concentration is same as the plasma levels. INH undergoes – N – acetylation and hydrolysis which is genetically, regulated. Patients are either slow or rapid acetylators which determine rate of metabolism of INH. Slow acetylators usually have higher blood levels for longer time (3 – 5 hours ) therefore have more side effects. Excreted in the urine as both unchanged drug and its metabolites. Duration of plasma levels is 6 hours.

Clinical Information

Indications

·    First line of drugs used in the treatment of tuberculosis along with rifampicin, pyrizinamide and ethambutol  given in regimens lasting for 6 – 9 months.

·    Chemoprophylaxis of tuberculosi

Dosage

Tablet :

·    Usual dose 5  - 10 mg/kg daily given (maximum 300 mg) in a single dose.

·    Children under 4, should receive 5 mg/kg/day.

·    In twice weekly regimes – 15 mg/kg, (maximum 699 mg).

·    In military and meningeal tuberculosis  - 10 – 15 mg/kg daily.

·    In chemoprophylaxis 5 mg/kg daily , for 6 months.

            Duration – upto 6 months.

Route of Adminstration     Oral.

Contraindications

·    Preexisting liver disorders like – hepatitis, hepatic failure, alcoholic liver disease etc.

·    Hypersensitivity reactions to isoniazid.

Precautions / Practice points :

·    Pyridoxine (10 mg / 100 mg of  INH ) should also be given with INH (in  high dose , intermittent therapy as in biweekly regimens) because  INH being a structural analogue of B6, competes with it in physiologic reactions and by competitive inhibition, interferes with B6 utilization causing effects like peripheral neuritis. Patients groups at risk, for developing these effects are diabetics, alcoholics and severely malnourished. B6 should be given to these patient groups.

·    Evaluate SGOT and SGPT levels at monthly intervals and instruct patient to report immediately if symptoms of hepatitis (anorexia, malaise, fatigue, nausea, jaundice) develop. Risk factors for development of hepatotoxicity are ; age over 60 years; preexisting liver disease; alcoholics. A mild increase in SGOT and SGPT levels does not warrant stopping treatment.

·    Can be used in pregnant and lactating mothers safely.

·    INH should  not be taken with cheese and fish as it may produce severe flushing, tachycardia, tachypnoea and sweating because INH has slight MAO inhibiting activity and may cause a tyramine like reaction with tyramine and histamine containing food.

·    In diabetes  mellitus, risk of increased neurotoxicity and a decreased control of diabetes  mellitus  due to hyperglycemia induced by INH may occur.

·    Administration Instructions :

-  May be taken with food.

- Alcohol abstinence is essential due to risk of hepatotoxicity.

Drug Interactions :

Potentially fatal :

·    INH inhibits cytochrome P450 enzyme and may cause toxicity of drugs like phenytoin,
barbiturates, carbamazepine, benzodiazepines. Theophylline.

·    INH increases the toxicity of phenytoin, carbamazepine and ethosuximide excretion by the  kidney.

Non fatal :

·    Effects of oral anticoagulants are enhanced.

·    PAS inhibits INH metabolism and increases its toxicity.

·    Antacids inhibits INH absorption.

·    Corticosteroids decreases serum INH levels.

·    Plasma concentration of  ketoconazole may be reduced.

Adverse Effects

Common effects:

·    GIT – anorexia, abdominal  pain.

·    Hepatotoxicity – multilobular hepatic damage caused by the metabolite – acetylhydrazine, manifested as increased SGOT and SGPT levels and symptoms of liver dysfunction – anorexia, nausea, vomiting, fatigue, malaise and jaundice.

·    Neurotoxicity – peripheral neuritis, insomnia, muscle twitching , restlessness, dizziness, paresthesias, rarely convulsions, impairments of higher functions may occur.

Rare effects :

·    Hypersensitivity – rashes, fever, urticaria, purpura.

·    Haematotoxicity -  agranulocytosis, eosinophilia, thrombocytopenia, anemia.

·    Pyridoxine deficiency, pellagra.

·    Endocrine disturbances like hyperglycemia and amenorrhoea.

·    SLE like syndrome.

·    Arthralgia and arthritis.

Drug  Toxicity

Earliest manifestations are nausea, vomiting, dizziness, slurring of speech, blurring of vision, visual hallucinations, Later – respiratory distress, CNS depression (stupor, progressing to coma), fits, metabolic acidosis and hyperglycemia occurs.

Treatment of Toxicity

·    Airway and respiratory control.

·    If convulsions – IV barbiturates.

·    IV pyridoxine ( 1 mg for every mg of INH ingested).

·    Control of acidosis and electrolyte imbalance, blood glucose levels.

·    Forced osmotic diuresis to increase the renal excretion of the drug.

·    Haemodialysis or peritoneal dialysis may be helpful.

·    Diazepam for seizures.

Storage

            Store in airtight containers protected from light. Incompatible with sugars.

Shelf Life                    2 years.

ETHAMBUTOL

General  Information

Drug Code                              Preparation                            Strength

     132                                     Tab. Ethambutol                       200 mg

     132                                     Tab. Ethambutol                       800 mg

Description of the Drug

Ethambutol is first line agent used in the multi-drug treatment of tuberculosis in the intensive 8 weeks phase of standard ATT regimen.

Mode of Action

            It is a bacteriostatic agent against M. tuberculosis.

            It acts by interfering with RNA synthesis.

Pharmacokinetics

About 80% is absorbed from the GIT. Peak plasma levels occurs 2 – 4 hours  after ingestion. It is widely distributed. It diffuses into the CSF, when the meninges are inflamed. It is excreted in the urine, 50 % as unchanged and the rest as metabolites.

Clinical Information

Indications

In the treatment of TB as a component in multidrug regimens, in the initial 2 months intensive phase.

Dosage

            15 – 25 mg/kg as a single daily dose, maximum 2.5 g day.

Route of Administration  Oral

Contraindications :

·    Patients with optic neuritis and visual difficulty.

·    Known hypersensitivity.

·    Children below 5 years ( as resting of visual acuity is not possible).

Precautions / Practice Points :

·    Ocular examination is recommended before treatment with ethambutol and advice patients  to report visual disturbances immediately, because if the drug is stopped early enough, the process is reversible.

·    Reduction of dosage in renal impairment should be done. (see appendix).

·    Use with caution in children  below 13 (as symptoms of toxicity may not be recognized by the patient) and in pregnancy.

Drug Interactions

Non fatal :

Concomitant use of ethambutol with aluminum salts may delay its absorption.

Adverse Effects

Common effects :

·    Retrobulbar neuritis with a reduction in visual acuity; constriction of visual field, central or peripheral scotomas and green-red colour blindness. One or  both eyes may be affected.

·    Gastro – intestinal disturbances such as metallic taste, nausea, vomiting, anorexia and abdominal pain.

Rare effects :

·    CNS effects like confusion, headache, dizziness.

·    Peripheral neuritis.

·    Jaundice or transient liver dysfunction.

·    Joint pains due to hyperuricemia.

·    Skin rashes, prurities.

Drug  Toxicity

Symptoms are decrease in visual acquity, anorexia, joint pain, numbness of extremities and CNS symptoms.

Treatment of Toxicity

·    Lavage and emesis to remove unabsorbed poison.

·    Sysmptomatic therapy.

Storage          

            Keep in a cool, dry place.

Shelf Life                    5 years.

PYRAZINAMIDE

General  Information

Drug Code                              Preparation                                           Strength

   135                                       Pyrazinamide                                           500  mg

Description of  the Drug

            Pyrazinamide is pyrazine analogue of nicotinamide.

Mode of Action

It is bactericidal to actively dividing organisms. The mechanism of action is unknown and possibly acts by lowering the PH of the organism. It is effective against intracellular organisms.

Pharmacokinetics

It is readily absorbed from the GIT and well distributed in all tissues especially CSF. Plasma half life is 6 – 8 hours. It is metabolized in the liver and excreted in the urine.

Clinical  Information

Indications

Treatment of tuberculosis – as a component of multidrug regimen in the initial intensive 2 months phase of 6 – 9 months of antituberculous treatment.

Dosage

            15 –30 mg/kg, maximum of 2 gm/day.

            Patients under 50 kg  - 1.5 gram daily.

            Patients more than 50 kg – 2 gram daily.

            In biweekly regimens, 50 mg/kg or 2.5 gm can be administered.

            Duration – upto 6 months.

Route of Administration    Oral :

Contraindications

·    Severe hepatic damage.

·    Hypersensitivity.

·    Acute gout.

·    Porphyria.

Precautions / Practice Points

·    Pyrazinamide blocks urate excretion. Therefore, hyperuricemia and gout may occur. So uric acid levels to be done before treatment and monitored regularly during treatment.

·    Should be used with caution in  patients with renal or hepatic dysfunction. Liver function tests to be done before therapy and SGOT and SGPT levels, to be monitored during treatment especially in alcoholics, patients with preexisting liver diseases. Instruct patients strictly to abstain from alcohol and to report immediately if symptoms of hepatotoxicity like anorexia, nausea, malaise and jaundice occur.

·    Care to be taken in diabetes mellitus patients as management of diabetes mellitus is difficult with patients on pyrazinamide.

·    Acid  peptic disease may be aggravated.

Drug Interactions

Probenecid blocks the excretion of pyrazinamide precipitating hyperuricaemia and gout.

Adverse effects

Common Effects :

·    Hepatotoxicity with transient increase in liver enzyme values – SGOT and SGPT.

·    Hyperuricaemia may lead to attacks of gout and arthralgia.

·    GIT – anorexia, nausea, vomiting.

Rare effects :

·    Myalgia, malaise, fever.

·    Sideroblastic anaemia, thrombocytopenia.

·    Photosensitivity and skin rashes.

Drug Toxicity

            Hepatotoxicity, acute attack of gout and gastric disturbances.

Treatment of toxicity

            Clinical monitoring and supportive treatment following gastro – intestinal

decontamination.

Storage

            Keep in a cool dry place.

Shelf Life                    3 years.

6.3      Antifungal

POVIDONE IODINE

General   Information

Drug Code                  Preparation                                                                 Strength

    454                          Povidone iodine scrub solution  100mg/5ml

      59                          Tab. Vaginal Pessaries                                       200 mg

    491                          Povidone iodine oint                             5 %

    342                          Povidone iodine  solution                      5 %

Description of the Drug

It is a complex of iodine with a surface acting agent called povidone. This combination is used as a topical germicidal agent.

Mode of Action

It acts as an antiseptic and disinfectant by slow release of iodine to exert an effect against bacteria, fungi, viruses, protozoa, cysts and spores.

Pharmacokinetics

It is absorbed systemically only when applied on denuded skin. It is not absorbed when
applied on intact skin. Vaginal pessaries however, may cause systemic absorption of  iodine.

Clinical  Information

Indications

·    Preparation of skin and mucous membrane prior to surgery, minor procedures like catheterization, aspiration and injections.

·    5 % ointment – topical antiseptic in wounds, cuts, ulcers, burns, abrasions, sutures, for prophylaxis of infections.

·    Disinfectant for equipments, floors, etc.,

·    As skin cleaner (Surgical scrub ) for hospital operating room personnel.

·    As vaginal pessaries in vaginal infections or preoperatively before surgeries.

Dosage

·    Topical application – as 5 % solution/ointment.

·    Vaginal pessary – 200 mg pessary once or twice a day – 14 days.

·    Preoperative scrubbing – scrub solution – as required, without dilution.

Routes of Administration :         Topical and vaginal.

Contraindications :

·    Excessively denuded skin.

·    Known iodine hypersensitivity.

·    Patients on lithium therapy.

Precaution / Practice Points

·    An exposure time period of 5 – 10 minutes is necessary for action of iodine for purposes of disinfection. If time of contact is decreased, the efficiency is reduced.

·    Efficacy of the disinfectant is reduced in the presence of organic matter, proteins and alkalis. Hence apply to precleaned surface.

·    High concentration of solution may cause partial thickness chemical burns, if applied for too long or over delicate skin. Hence, in preoperative preparation care must be taken to avoid pooling of solution beneath the patient.

·    Use vaginal pessaries with caution in thyroid disorders, renal impairment and only if absolutely essential in pregnancy and lactation – since systemic absorption is high.

·    Avoid use in under 2 years of age.

·    Avoid contact with eyes.

·    Administration Instructions :     

-  Moisten vaginal pessary before insertion.

Drug Interactions

            Iodine alters lithium levels in patients on lithium carbonate therapy. Hence, do

not use on patients stabilized on lithium.

Adverse Effects

Rare effects :

Hypersensitivity reactions like redness, irritation, burning or stinging sensation in susceptible individuals.

Drug Toxicity

Only if systemic absorption occurs. Difficulty in breathing excessive sweating and  salivation , metabolic acidosis, hypernatremia, and impairment of renal function may occur.

Treatment of Toxicity

             Removal of contact with drug and symptomatic treatment.

Storage

            Store in airtight containers.

Shelf Life

            Tab vaginal pessaries -              :

            Povidone iodine solution                       :     2 years.

            Povidone iodine oint                             :

            Povidone iodine scrub solution                 1 year.

GRISEOFULVIN

General   Information

Drug Code                              Preparation                                        Strength

         73                                                           Tab. Griseofulvin                                  125mg

Description of the Drug

Griseofulvin is an antifungal substance produced by the growth of certain strains of Penicillium griseofulvum.

Mode of Action

It is mainly fungistatic, which inhibits the growth of various species of Trichophyton, Microsporum and epidermophyton by interfering with microtubule formation. It is deposited in the precursor cells of the epidermis and bound to newly formed keratin , which then becomes resistant to fungal invasion.

Pharmacokinetics

Irregularly absorbed from GIT , but absorption is enhanced by administration with a fatty meal. It is concentrated in the stratum corneum. It is metabolized by the liver and mainly excreted in urine and some amount in sweat and faeces. It is a potent inducer of hepatic microsomal enzyme systems.

Clinical Information :

Indications

·    Mycotic disease of the hair and nails like T.barbae, T.capitis, T.Unguinum.

·    Resistant fungal infections of the skin like T.corporis, T.cruris, T.pedis, T.manus.

Dosage

Children

            10 mg/kg body weight.

Adults

            500 mg – 1 gm (500 mg b.d); upto a maximum of 1.5 – 2 g daily

      -  for extensive infections of toes, finger nails.

Duration

Duration depends upon the nature of disease.

            T. capitis                      - 4 – 6 weeks.

            T. corporis                   - 2 – 4 weeks.

            T. pedis                        - 4 – 8 weeks.

            T. unguinum                 

-   finger nails                - 6 months

            -   toe nails                   - 9 months

Routes of Administration        Oral, Topical.

Contraindications

·    Porphyria.

·    Hepatic failure.

·    Hypersensitivity to griseofulvin.

·    Pregnancy.

Precautions / Practice Points

·    While on treatment general measures in regard to hygiene should be observed to prevent reinfection.

·    Use with caution in patients with SLE (can precipitate attacks).

·    Avoid sunlight since it can precipitate a photosensitivity reaction.

·    Periodic monitoring of renal, hepatic and haematopoietic function, when on long term alcohol.

·    Instruct patients to abstain from  alcohol.

·    May impair performance of skilled tasks – instruct patients not to drive or operate machinery.

·    It is reported to be embryotoxic and teratogenic. Female patients to avoid pregnancy while on treatment and male patients wait till 6 months after stopping treatment before fathering a child.

·    Administration Instruction :

-  Administer with meals.

Drug Interaction

Potentially fatal :

·    Induces hepatic microsomal enzymes thereby reduces the anticoagulant activity of warfarin and cyclosporin.

Non fatal :

·    Reduces the efficacy of some oral contraceptives and break through bleeding  episodes can occur; other methods of contraception are advised.

·    Barbiturates reduces the absorption of griseofulvin.

·    It can cause antabuse like reaction with alcohol.

Adverse Effects

Common effects :

·    GIT – nausea, vomiting, diarrhea,  epigastric pain.

·    Headache – usually is relieved as therapy continues.

Rare effects :

·    Hypersensitivity reactions like skin rashes, urticaria, erythema multiforme, fixed drug eruption, toxic epidermonecrolysis may occur.

·    After prolonged theraphy, paraesthesias of hands and feet may occur.

·    CNS – depression, confusion, dizziness, insomnia, fatigue.

·    Haemotologic – leucopenia, neutropenia, agranulocytosis may occur.

Drug Toxicity

            Lethargy, vertigo, blurred vision, nausea, vomiting and diarrhoea.

Treatment of Toxicity

            Withdrawal of the drug and supportive therapy.

Storage

            Keep in a cool, dry place.

Shelf Life                    3 years.

KETOCONAZOLE

General  Information

Drug Code                              Preparation                            Strength

    355                                       Tab. Ketoconazole                  200mg

Description of  the Drug

Ketoconazole is an orally effective, imidazole antifungal agent.

Spectrum of action :

·    Dermatophytes : Trichophyton, Microsporum, Epidermophyton species.

·    Candida.

·    Malassia furfur.

·    Blastomyces species, coccidiomyces, Histoplasma, Cryptococcus.

Mode of Action

It interferes with ergosterol synthesis and therefore alters the permeability of the cell membrane to sensitive fungi causing leakage of intracellular compounds and death of cell.

Pharmacokinetics

Oral absorption is facilitated by gastric acidity. It is more soluble at lower pH and better absorbed. Hepatic metabolism is extensive and excretion is mainly through faeces and urine. Does not enter CSF or brain in clinically significant amount, hence cannot be used for CNS fungal infections.

Clinical Information

·    Systemic fungal infections :

Candidiasis – chronic mucocutaneous candidiasis, resistant to other forms of therapy.

                  - Oral and esophageal candidiasis.

Blastomycosis.

            Coccidiomycosis, Paracoccidiomycosis.

Histoplasmosis.

·    Resistant cutaneous dermatophyte infections in skin and nails.

·    Porphylaxis of mycoses in immunosuppressed patients.

Dosage

Adult   - 200 mg once daily taken with food : increased to 400 mg in severe infections, for 14 days or till one week after symptoms have subsided.

Children – 3 mg/kg.

            1 – 4 years       - 50 mg

            5 – 12 years     - 100 mg.

For vaginal candidiasis – 400 mg daily for 5 days.

Route of Administration     Oral :

Contraindications

·    Coadministration with terfenadine, astemizole, cisapride.

·    Pregnancy and lactation ( It is teratogenic).

·    Preexisting liver disease, hepatic dysfunction.

·    Prophyria.

Precautions / Practice Points

·    Liver function tests should be performed before commencement of treatment with ketoconazole, and then at least monthly throughout the treatment. Instruct patients to report immediately if anorexia, nausea, fatigue or jaundice develops.

·    Not effective against fungal meningitis since CSF penetration is very poor.

·    Do not use for superficial fungal infections.

·    Administration Instruction :

-  Administer with food for better absorption.

Drug Interactions

Ketoconazole is a potent inhibitor of hepatic enzymes. Hence increases the serum  levels of drugs metabolized by cytochrome P450 enzyme systems.

Potentially fatal :

·    Increases serum concentration of astemizole, terfenadine and cisapride leading to QT prolongation and serious ventricular arrhythmias.

·    Effects of oral anticoagulants are increased – risk of major bleeding episodes.

·    Effects of oral hypoglycemic are increased – risk of hypoglycemic attacks.

·    Digoxin levels are increased – digoxin toxicity may occur.

·    Phenytoin levels are increased may lead to toxicity.

·    Serum cyclosporin levels are increased – risk of toxicity.

·    Theophylline metabolijm is inhibited – leading to risk of toxicity.

Non fatal :

·    Antacids, H2 blockers, proton pump inhibitors like omeprazole, sucralfate and antimuscarinics reduces absorption of ketoconazole by reducing gastric acidity.

·    Rifampicin accelerates ketaconazole metabolism.

·    Amphotericin effects may be antagonized.

·    Reduced metabolism of benzodiazepines  - increased sedative effects.

Adverse Effects

Common effects :

·    Nausea, vomiting, abdominal pain.

·    Pruritis.

Rare effects :

·    Most serious is risk of hepatotoxicity – hepatitis and reversible hepatic damage may occur.

·    Increased intracranial pressure – papilledema, headache, dizziness, bulging fontanelles, neuropsychatric disturbances, parasthesias and photophobia.

·    Gynaecomastia, oligosopermia (due to inhibition of steriodogenesis), alopecia.

·    Hypersensitivity – skin rashes, urticaria may occur.

·    Thrombocytopenia, leucopenia etc, may occur.

Drug toxicity

Symptoms are dizziness, headache, vomiting, cardiac or hepatotoxicity may occur.

Treatment of Toxicity

·    Gastric lavage with sodium bicarbonate to decrease absorption.

·    Supportive measures.

Storage

            Store in airtight containers.

Shelf Life                    3 years.

WHITFIELDS  OINTMENT

General  Information

Drug Code                          Preparation                                 Strength

   418                                   Whitfields Ointment                Benzoic acid – 6 %

                                                                                          Salicylic acid – 3 %

Description of the Drug

Benzoic acid :

Anti fungal and anti bacterial agent  with broad spectrum of action when used in acidic medium of pH less than 5.

Salicylic acid :

            Keratolytic agent.

Mode of Action

·    Benzoic acid – it acts by reducing the intracellular pH of organisms. It has a fungistatic action with some antibacterial properties.

·    Salicylic acid  - It is keratolytic effect helps remove  infected tissue and promotes penetration of benzoic acid. It also helps to provide an acidic medium for action of benzoic acid.

Pharmacokinetics

Benzoic acid is not absorbed via skin. Salicylic acid which may be absorbed, is slowly excreted by the urine.

Clinical  Information

Indications

Various fungal infections – dermatphyte infections like Tinea cruris, T.corporis, T.manus, T.pedis, T.capitis and T.barbae.

Dosage

            As required;  apply twice daily.

Route of Administration

            External application only.

Contraindications

·    Broken or inflamed skin.

·    History of known hypersensitivity or allergic reaction.

Precautions / Practice Points

·    Should not be applied excessively over a large surface area, since salicylic acid can be absorbed through the skin and cause toxicity especially in children; states of hepatic and renal dysfunction. Avoid us in children less than 2 years of age.

·    Benzoic acid is a slow acting fungistatic, weaker than most antifungals, hence long duration of contact is needed for its antifungal action. Also eradication of infection takes place only when affected stratum corneum is shed – hence, duration of therapy also should last for weeks to months.

Adverse Effects

·    Salicylic acid is an irritant and application to delicate skin may cause dermatitis.

·    Benzoic acid may cause allergic reactions in susceptible individual. Irritation of eyes and mucous membranes can also occur.

Drug Toxicity

Accidental ingestion, or wide spread application of large doses of the drug to large surface areas may cause systemic absorption of salicylate and hence salicylic acid poisoning, especially in children.

Treatment of Toxicity

            Treat as for salicylate poisoning – correction of metabolic acidosis etc.,

Storage

            Protect from light.

Shelf Life                    3 years.

NYSTATIN

General  Information

Drug Code                             Preparation                                      Strength

    446                                     Nystatin pessary                      1,00,000 units/ pessary

Description of the Drug

It is antifungal substance by the growth of certain strains of streptomyces noursei. It is a tetraene macrolide and was named nystatin, because it was discovered in the New York state health laboratory.

Mode of Action

It interferes with the permeability of the cell membrane of sensitive fungi by binding  to sterols, chiefly ergosterol and alters membrane permeability. Depending upon concentration it can act either as a fungistatic or a fungicidal agent.

Pharmacokinetic

It is not absorbed from the GIT, skin or the mucous membranes. Action of drug is rapid and relief is obtained in 24 – 72 hours. It is too toxic for systemic use.

Clinical  Information

Indications

·    Treatment of vaginal candidiasis.

·    Prophylaxis of vaginal candidiasis in immunocompromised individuals.

Dosage

Pessary containing 1 lakh units is inserted, once daily at bed time for 2 weeks.

Route of Administration    Intravaginal :

Contraindications

            Hypersensitive reactions.

Precautions / Practice Points

            It can be used safely in pregnant women and lactating mothers.

Adverse Effects

            Are rare

Locally – only mild irritation, sometime allergic skin reactions like exfoliative dermatitis may be seen.

Drug Toxicity

            Well tolerated by all age groups.

Storage

            Store at a temperature between 2 to 8o c.

            Protect from light.

Shelf Life                    2 years.

CLOTRIMAZOLE CREAM

General  Information

Drug Code                              Preparation                                        Strength

      449                                   Clotrimazole cream 2 %                       15 gm Tube.

Description of the Drug

Clotrimazole is a broad spectrum antifungal agent, used for the treatment of superficial dermatophyte infections.

Spectrum of Action :

·    Trichophyton, epidermophyton, Microsporon species.

·    Candida species.

Mode of Action

It is an imidazole antifungal agent, which interferes with ergosterol synthesis and therefore alters the permeability of the cell membrane causing leakage of intra cellular compounds, thereby killing the fungus. Main action is against dividing and growing organisms.

Pharmacokinetics

When applied topically clotrimazole penetrates the epidermis, but there is no systemic absorption. Duration of action is 6 – 8 hours.

Clinical Information

Indications

·    Tinea Versicolor.

·    Tinea infections like T.corporis, T.cruris, T.pedis, T.manus, T.capitis etc.,

·    Candidiasis – cutaneous or vulvovaginal.

Dosage

            2 % cream applied 2 – 3 times daily , for 14 days.

Route of Administration   Topical .

Contraindications

            Known hypersensitivity.

Precautions / Practice Points

            Avoid contact with eyes. Use with caution in children under 3 years of age.

Adverse Effects

Local reactions – irritation, burning sensation, erythema,blistering, peeling, edema, urticaria may occur.

Storage

            Protect from light.

Shelf Life                     3 years.

6.4        Anti protozoal Drugs.

6.4.1.    Anti amoebic.

METRONIDAZOLE

General  Information

Drug Code                              Preparation                                        Strength

     7                                        Tab. Metronidazole                               200 mg

  172                                       Inj.  Metronidazole                                500 mg /100 ml.

  356                                      Metronidazole  Benzoate

                                        Oral suspension                                      100 mg/5 ml.

Description of the Drug

            It is an imidazole derivative with antimicrobial activity spectrum of action :

Spectrum of action:

Protozoa :

            E. histolytica, Trichomonas, Giardia, Lambia, Balantidium coli.

Anaerobes :

            Bacteroides, clostridium, fusobacteria, Peptococcus.

Mode of Action

It is a bactericidal agent, acts by forming reduced cytotoxic compounds that bind to proteins and DNA of the organisms resulting in death. It kills only the trophozoites and not the cysts E.histolytica.

Pharmacokinetics

On oral administration it is completely absorbed and widely distributed. (Hence must be combined with a luminal amoebicide for treatment of intestinal amoebiasis). Plasma half life is 8 hours, which is prolonged in impaired liver function. It is excreted in the urine as metabolites. It is secreted in breast milk and crosses the placental barrier.

Clinical Information

Indications :

·    Treatement of susceptible protozoal infections like  E.histolytica, Giardia, lambia, B.coli, G.intestinalis and T.vaginalis.

·    Treatment of anaerobic bacterial infections – intra abdominal infections, peritonitis, septicaemia and infective endocarditis.

·    Prophylaxis of post operative anaerobic infections in surgeries like appendicectomy, colorectal surgery, etc.,

·    Specific bacterial infections like acute necrotizing ulcerative gingivitis (Vincent’s angina) and pseudomembranous colitis.

·    To eradicate H.pylori in pepetic ulcer in combination with other compounds.

·    Inflammatory bowel disease.

Dosage

AMOEBIASIS

            Adult

             800 mg 8th hourly for 5 – 10 days.

            Children

            1 –3 years – 200 mg 8th hourly

            3 –7 years – 200 mg 6th hourly.

            7 – 10 years – 400 mg 8 th hourly.

GIARDIASIS

            250 mg three times daily for 5 – 7 days.

TRICHOMONIASIS

            Treat the partner also.

            7 days course of 250 mg three times daily.

For surgical prophylaxis – 400 mg 8th hourly, orally , 24 hours  before surgery  

resumed postoperatively by I.V.500 mg 8th hourly until the oral regime can be started.

Acute necrotizing ulcerative gingivitis

            Adult

200 mg 8th hourly for 3 days.

            Children

            1 – 3 years – 50 mg 8th hourly for 3 days.

            3 – 7 years – 100 mg 12th hourly for 3 days.

            7 – 10 years – 100 mg 8th hourly for 3 days.

Anaerobic bacterial infections

            Adult

            Oral :  Initial dose of 800 mg followed by 400 mg every 8 hours for 7 years.

            I.V : 500 mg 8th hourly for 7 days.

            Children

            7.5 mg/kg, 8th hourly.

            Duration 7 – 10 days.

Routes of Administration     Oral,     I.V.

Contraindications

·    Early pregnancy, (first trimester) due to possible teratogenicity.

·    Location.

Precaution / Practice Points

·    Use with caution in patients with hepatic dysfunction, reduction of dose is advised (see appendix).

·    Should be used with caution in patients with blood dyscrasias and CNS disorder.

·    All  patients receiving metronidazole for  more than 10 days should be monitored and treatment discontinued if signs of peripheral neuropathy or CNS toxicity develop.

·    Instruct patients to abstain from alcohol during therapy and for 48 hours after stopping it.

·    Administration Instruction :

-  Give tablets with or after meals.

      -  Give oral suspension 1 hour before meals.

      -  Give I.V. infusion over 30 – 45 minutes.

Drug Interactions

Potentially fatal :

·    It increases the serum lithium levels and its toxicity.

·    It potentiates the effects of oral anticoagulants and may cause major bleeding episodes.

Non fatal :

·    When given with microsomal enzymes inducers like barbiturates, its efficacy is reduced.

·    When given in conjunction with alcohol, metronidazole may provoke a disulfuram like reaction.

·    Metronidazole inhibits phenytoin metabolism.

Adverse Effects

Common effects :

Gastro – intestinal disturbances – nausea, unpleasant metallic taste, anorexia, vomiting ,
diarrhoea, dry mouth, furred tongue, glossitis and stomatitis.

Rare effects :

·    Weakness, dizziness, ataxia, drowsiness, insomnia changes in mood, paraesthesias, convulsions, are reported to  occur in very high doses.

·    Hypersensitivity – rashes, urticaria or angioedema may occur.

·    Darkening of the urine.

·    Thrombophlebitis following I.V. adminstration of metronidazole.

·    Vaginal candidiasis.

·    Leucopenia.

Drug Toxicity

Nausea, vomiting, ataxia, peripheral neuropathy and convulsions may occur on intake of more than 6 – 10 gm /day for 5 – 7 days continuously.

Treatment of Toxicity

·    Discontinue the drug

·    Symptomatic treatment.

Storage

Tablets and suspension should be stored in well closed containers, protected from light. Metronidaz zole injection should be kept protected from light.

Shelf Life                      3 years.

6.4.2.              Anti Malarial

CHLOROQUINE

General  Information

Drug Code                              Preparation                                          Strength

     450                                      Tab. Chloroquine phosphate                    250 mg

Description of the Drug

Choloroquine is a 4 – aminoquinoline used primarily as an antimalarial and also as a tissue amoebicide.

Mode of Action

·    Choloroquine is concentrated in parasitized RBC and acts by prevention of nucleoprotein synthesis in protozoal cells. Its main effect is on erythrocytic form (blood schizonticide) of all 4 plasmodium species and gametocytes of P.Vivax,P.ovale, P.malariae (gametocide). It is not effective against pre-erythrocytic and exo erythrocytic forms and gametes of P.falciparum.

·    Chloroquine also has anti inflammatory and amoebicidal properities.

Pharmacokinetics.

It is rapidly absorbed from the GIT , concentrated in organs like liver, spleen, kidney and retina. Hence for adequate plasma levels, initial large loading dose is needed. Crosses the placenta, secreted in milk. It is partially metabolized in the liver and excreted in the urine, mostly unchanged. In acute attacks, parasitemia is cleared by 48 – 72 hours.

Clinical Information

Indications

·    Treatment of acute attacks of malaria.

·    Chemoprophylaxis of malaria caused by P.falciparum and P.vivax.

·    Treatement of extraintestinal amoebiasis and giardiasis.

·    Autoimmune disorders – rheumatoid arthritis, juvenile arthritis, sjogrens syndrome, SLE etc.,

Dosage

Note    :    1 gm = 4 tablets of chloroquine phosphate = 600 mg of chloroquine base.

500 mg  = 2 tablets of chloroquine phosphate = 300 mg of chloroquine base.

In acute attacks.

Adult

600 mg of base followed after 6 hours by 300 mg of base, then 300 mg of base daily for next 2 days.

Children

            Initial dose – 10 mg/kg followed by 5 mg/kg after 6 hours prophylaxis

Prophylaxis

            300 mg of chloroquine base/week – starting 2 weeks before and 4 weeks after

 visit to endemic areas.

Routes of Administration     Oral, IM, IV.

Contraindications

·    Known hypersensitivity.

·    In psoriasis and porphyria patients , in which the disease might be precipitated.

·    Retinal  and visual field abnormalities are Contraindications for long term therapy.

Precautions / Practice Points

·    Use with caution in patients with impaired liver function, chronic alcoholics, epileptic patients , G6PD deficiency patients (may precipitate haemolysis ) and neuromuscular disorders like myasthenia gravis.

·    Eyes should be examined before starting long term treatment and should monitored subsequently at frequent intervals (3 months). Periodic blood counts are also advised.

·    Can be used in pregnancy since the benefits of the drug out weighs risks of untreated malarial infection.

·    Administration Instruction :

-  Administer with meals or use an antiemetic such as domperidone to reduce GI side effects.

Drug Interactions :

Potentially fatal :

            Chloroquine increases the risk of ventricular arrhythmias with amiodarone.

            Antagonism of antiepileptics and precipitation of convulsions may occur.

            It increases the serum levels of cyclosporin and risk of toxicity.

Non fatal :

            Antacids reduce the absorption of chloroquine.

May diminish effects of neostigmine and pyridostigmine in the treatment of myasthenia.

Adverse Effects

Common effects:

            GIT – nausea, vomiting, anorexia, diarrhoea, abdominal cramps.

Rare effects :

            Occurs in long term therapy.

Ocular reaction – blurring of vision, nyctalopia, scotomas and difficulty in accommodation.

            CNS – headache, psychosis, tinnitus, personality changes.

            Cardio vascular – ECG changes and hypotension.

            Pruritis.

 Blood dyscrasias may occur.

Drug Toxicity

            In children below 3, doses of 1 gram are toxic.

Symptoms – headache, visual disturbances, nausea, vomiting, cardiac and respiratory collapse, convulsions may occur. ECG shows prolonged conduction  time  and  bradycardia.

Treatment of Toxicity

            Emesis, gastric lavage (activated charcoal within 30 minutes of ingestion).

            ECG and CVS monitoring.

            If convulsions – treat by diazepam or barbiturates.

            If hypotension – phenylephrine or vasopressors.

            Artificial respiration if respiratory arrest occurs.

Storage

Protect from light and moisture.

Shelf Life                    2 years.

PRIMAQUINE

General  Information

Drug Code                              Preparation                                        Strength

        451                                   Tab. Primaquine                                  2.5 mg

Description of the Drug

Primaquine is a synthetic 8 aminoquinoline, used to produce radical cure and prevent relapse of vivax and ovale malaria

Mode of Action

It is effective against gametocytes of all species especially P.falciparum (gametocidal ) and against exoerythrocytic forms of P. vivax and P.ovale (tissue schizonticidal) . However it is not effective against erythrocytic forms and cannot be used to treat acute attacks.

Clinical Information

Indications

·    To produce radical cure of P.vivax and P.ovale, administered along with chloroquine.

·    In the treatment of relapse of P.vivax and P.ovale, primaquine is given for 2 weeks  (after treatment of the acute attack by chloroquine ).

·    In high  risk areas, primaquine is given along with chloroquine as a part of the presumptive treatment as s single dose.

Dosage

For radical cure :

Adult   - 12 mg of the base daily for 14 days in 2 divided doses.

Children          - 0.3 mg /kg body weight daily for 14 days.

(Note : As per the NMEP program , primaquine treatment for 3 days is as  follows. ).

Age in                                      P.vivax                                    P.falciparum

Years        —————————————————————————————————————————————       

1 –  4                 5 mg                 5 mg               2.5 mg                          10 mg

4 –  8               10 mg               10 mg                  5 mg                          20 mg

8 – 14              20 mg               20 mg               10 mg                          30 mg

> – 14             30 mg               30 mg               15 mg                          40 mg

For presumption treatment in high risk areas :

            Single dose of 45 mg of primaquine along with 600 mg of chloroquine.

Route of Administration    Oral :

Contraindications

·    Pregnancy.

·    Infants under 1 years.

·    In acutely ill patients suffering from systemic disease characterized by tendency to granulocytopenia.

·    (e.g.  very active forms of rheumatoid arthritis and lupus erythematosus and other autoimmune disorders.)

Precautions / practice Points :

·    Primaquine should be delayed until the acute stage of malaria has been brought under control by a blood schizonticide, because of the risk of inducing haemolysis when both drugs are administered  together.

·    Periodic monitoring of blood counts while on therapy.

·    Because of the possibility of haemolysis, the drug should be used with caution in patients with glucose – 6 – phosphate dehydrogenase deficiency – any darkening of urine or symptoms of anemia should be reported and blood counts and examination of urine for hemolysis should be undertaken.

·    Do not use in pregnancy  : administration of radical cure with primaquine can be delayed until after delivery.

·    Administration Instructions :

-  Give after food.

Drug Interactions

Potentially fatal :

·    Primaquine should be avoided with

-  potentially haemolytic drugs.

   -  drugs that depress myeloid elements of marrow.

   -  Drugs that produce methaemoglobinemia.

Non fatal :

·    Mepacrine increases plasma levels of primaquine.

Adverse Effects

Common effects :

·    GIT  -  abdominal pain, epigastric distress, nausea, vomiting.

Rare effects :

·    Haematological – methaemoglobinaemia, haemolytic anaemia in patients with G6PD deficiency.

·    Leucopenia . agranulocytosis.

·    CVS – cardiac arrhythmias, hypotension.

·    Headache.

Drug Toxicity

Toxicity is more common in patients with G6PD deficiency, in whom haemolysis occurs, which can result in progressive haemoglobinaemia, haemoglobinuria leading to death. High doses (60 – 240 mg) can cause  abdominal, symptoms, vomiting, cyanosis, methemoglobinemia and leucopenia. Chronic overdose can result in ototoxicity and retinopathy.

Treatment  of Toxicity

Supportive treatment – I.V. fluids, blood transfusion for hemolysis, methylene blue if methemoglobinemia is  severe.

Storage

            Protect from light.

Shelf  Life                    2 years.

PYRIMETHAMINE – SULPHADOXINE COMBINATION

General Information

Drug Code                              Preparation                                         Strength

     452                                     Pyrimethamine                                        25 mg

                                               + Sulphadoxine                            500 mg          

Description of the Drug

A combination of pyrimethamine (a inhibitor of protozoal dihydrofolats reductase enzyme) and sulphadoxine (a sulphonamide which inhibits formation of dihydrofolate) in the ration of 1 : 20.

Mode of Action

Sulphadoxine decreases the formation of dihydrofolic acid and phyrimethamine prevents its reduction to trtrahydrofolic acid. Hence, the act synergistrically to block folic acid synthesis and DNA formation in the protozoan. The drug is effective against erythrocytic forms of chloroquine eseistrant P.falciparum species.

Pharmacokinetics      

It is completely absorbed from the GIT , with peak plasma concentration after 2 – 6 hours. It is concentrated in the kidneys, lungs, liver and spleen. 80–90 % is bound to plasma proteins. It is metabolized in liver and excreted in the urine.

Clinical Information

Indications

·    Pyrimethamine – sulfadoxine combination is used in treatment of chloroquine resistant P.falciparum malaria, either alone or in conjunction with quinine.

·    Prophylaxis of P.falciparum malaria, when traveling to endemic areas of chloroquine resistant P.falciparum.

Dosage

Adult

            2- 3 tablets (75 mg : 1.5 g of pyrimethamine : sulphadoxine as a single  dose.

Children

            Up to 4 years – half tablet.

            5- 6 years – one tablet

            7 –9 years – one and half tablets single dose.

            10 –14 years – 2 tablets single dose.

Route of Administration   Oral :

Contraindications

·    In patients with folate deficiency and megaloblasitc anaemia.

·    Pregnancy (especially first trimester and at term ) and in lactating mothers.

·    In infants.

·    Individuals allergic to sulphonamides.

Precautions / Practice Points

·    It is slow in action, hence cannot be used in treatment of acute attacks.

·    Use with caution in patients with impaired renal and hepatic function and G6PD deficiency (may precipitate haemolysis).

·    In malnourished individuals and in alcpholics, folate, deficiency may be precipitated.

·    Monitor blood counts in prolonged therapy (every 2 weeks).

·    Administration Instructions :

-  Take with meals to reduce the gastro – intestinal side  effects.

Drug Interactions

Non  fatal;

·    Pyrimethamine when given with other folate antagonists such as cotrimoxazole and
methotrexate increases the risk of bone marrow depression.

·    Phenytoin enhances antifolate effect.

Adverse Effects

Common effects :

·    GI – abdominal pain , anorexia, stomatitis, vomiting , nausea.

·    CNS – headache, neuritis, convulsions, ataxia etc.

Rare effects :

In individuals allergic to sulpha drugs, potentially serious adverse effects can occur :

·    Steven Johnson’s syndrome, toxic epidermal, necrolysis, erythema multiforme, utricaria,
serum sickness, exfoliative dermatitis and photosensitization.  If any indication of skin rash appears , discontinue drug immediately.

·    Blood – agranulocytosis, haemolytic anemia, methemoglobinemia, thromobocytopenia, aplastic anemia etc.

·    Pulmonary infiltrates can occur on long term therapy.

Drug Toxicity

Symptoms are abdominal pain, vomiting, anorexia, crystalluria, convulsions, thrombocytopenia and leucopenia.

Treatment of Toxicity

Emesis and gastric lavage. Adequate hydration to ensure diuresis. Administer  diazepam if convulsions occur and folinic acid if thrombocytopenia or leucopenia occurs, Monitor Kidney and haematopoietic functions.

Storage

            Protect from light.

Shelf Life                     2 years

6.5     Anti viral

ACYCLOVIR

General  Information

Drug Code                               Preparation                                        Strength

    359                                      Tab. Acyclovir                                       200 mg

    404                                     Inj.   Acyclovir                                        250 mg/vial

   360                                     Ointment Acyclovir                               5 % w/w

Description of the Drug

Acyclovir is synthetic analogue of guanine used in the treatment and prophylaxis of viral infection.

Mode of Action

It inhibits the viral DNA synthesis and replication by inhibiting the Herpesvirus DNA polymerase enzyme. It has no activity against latent viruses.

Pharmacokinetics

15 – 30 5% is absorbed from GIT, Following I.V. injection plasma acyclovir is eliminated in a biphasic pattern. Following topical application only small amount get absorbed through intact skin. It is widely distributed . Excreted through the kidneys . It crosses the placental barrier and small amount is secreted in the milk. Plasma half life is 2.5 – 3 hours.

Clinical Information

Indications Tab acyclovir :

·    Systemic treatment of herpes simples infection of skin and mucous membranes (genital herpes) both initial attacks and for suppression of recurrent disease.

·    Herpes zoster infections – acute treatment of H.zoster.

            Chickenpox – Varicella zoster infections.

·    Prophylaxis and prevention of recurrence of Herpes infections in the immunocompromised.

Ointment acyclovir :

·    Topical application in genital herpes simplex, both initial and recurrent epidsodes.

·    Muco cutaneous herpes lesions like herpes labialis.

IV Infusion :

·    Disseminated herpes infection in immunocompromised, AIDS patients.

·    Herpes encephalitis and in initial treatment of severe genital herpes.

·    Varicella zoster in immunocompromised or AIDS patients.

·    Prophylaxis of CMV, herpes infection in post transplant immunosuppression.

Dosage

Ointment – 5 %

Apply every 4 hours or 5 times daily for 5 – 10 days.

Tablets :

·    Genital herpes simplex – for adults and children over 2 years – 200 mg, 5 times daily for 5 days.

-     For child less than 2 years – half the adult dose.

-     In immunocopromised – double the dose.

-     For prevention of recurrence – 200 mg qid or 400 mg bd reduced gradually, for upto 6 months.

·    Varicella and Herpes zoster – adult – 800 mg 5 times daily for 1 week.

Child : 20 mg/kg (maximum 800 mg) qid for 5 days.

I.V. preparation :

·    For disseminated herpes simplex infection = 5 mg/kg every 8 hours for 5 days.

·    For encephalitis and Varicella zoster in immunocompromised patient – double the dose to 10 mg/kg.

Routes of Administration       Oral, I.V. infusion, Topical

Contraindications

·    Children below 6 months.

·    Renal failure

Precautions / Practice Points

·    Administer acyclovir as early as possible. Best results are obtained if given at onset of infection (within 48 hours).

·    Use with caution in patients with renal impairment and doses should be adjusted according to creatinine clearance.

·    Avoid combining with other nephrotoxic drugs.

·    Use with caution during pregnancy and in lactating mothers.

·    In dehydrated patients, rehydrate before administration of acyclovir or crystals may precipitate in renal tubules causing acute renal failure.

·    Monitor renal parameters (blood, urea, nitrogen, serum creatinine and urine analysis) and liver parameters while on therapy.

·    Administration Instruction:

-  Rapid or bolus injection should be avoided. Injection should be madeup in distilled water and then infused in normal saline or glucose solution over an hour.

- 5 % ointment should not be applied in the eye (only 3 % ointment to be applied in keratitis).

Drug Interactions

Non – fatal:

Probenecid increases the plasma concentration of acyclovir by decreasing excrection.

Adverse Effects

Common effects:

·    General – fever, headache, malaise and fatigue.

·    Local – thromobophlebitis on IV administration, hypotension may occur rarely.

Rare effects:

·    Confusion, dizziness, hallucinations, paraesthesia, tremors.

·    Rashes.

·    Rise in bilirubin and liver enzymes.

·    Renal impairment – rise in blood urea nitrogen and creatinine.

Drug Toxicity

Drug toxicity can occur when rapid and massive infusions are given. Anuria and renal failure may occur.

Treatment of Toxicity

·    Maintain adequate hydration and urine output.

·    Hemodialysis is highly effective.

·    Supportive and symptomatic treatments.

Storage

            Store in airtight chambers.

Shelf Life                   

            Acyclovir oint.  -           2 years.

            Acyclovir tab.               -           3 years.

            Acyclovir inj.                -           3 years.