2.   ANALGESICS, ANTIPYRETICS & ANTI INFLAMMATORY DRUGS                                                                                 

ASPIRIN

 

General   Information

Drug Code                                Preparation                                            Strength

            1                                    Tab. Aspirin.                                              300 mg           

Description of the Drug

Aspirin is a weak organic acid – acetyl salicylic acid.  It has antipyretic, anti-inflammatory and analgesic effects.  It also has antiplatelet activity.

Mode of Action

The antipyretic and anti-inflammatory effects of the salicylates are primarily due to the blockage of prostaglandin synthesis (by inhibiting cyclo-oxygenase enzyme irreversibly) at the thermoregulating centers in the hypothalamus and at peripheral target sites.  They also prevent the sensitization of pain receptors to both mechanical and chemical stimuli.  It has a uricosuric effect in large doses ( 5-6 gm/day).  But in doses generally used, it decreases urate excretion (1-2 gm/day).  Salicylates also causes hyperventilation by stimulation of respiratory center.

Pharmacokinetics

After oral adminstration, aspirin is well absorbed from the GIT and hydrolysed to salicylate and acetic acid in the tissues, where saliylate exerts its effects.  Onset of action is 15-30 min after ingestion ad lasts for 4-8 hours.  Salicylates crosses both the blood brain barrier and the placenta.  It undergoes hepatic metabolism and is excreted in the urine.

Clinical  Information 

Indications

Analgesic effect:  Short term adminstration for pain relief in myalgia, headache, arthritis, dysmenorrhoe, dental pain, postpartum pain etc.,

Antipyretic effect:  common cold, cough and fever due to any cause.

Anti-inflammatory effect:  For relief of pain and inflammation in high doses ( more than 3mg/day) and for prolonged periods in musculo skeletal disorders like osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, SLE, ankylosing spondylitis etc.

Antiplatelet effect:

Used in low doses for prolonged periods of time.

·  Preventionof recurrent myocardial infarction  - reduces mortality by 20% in acute myocardial infarction.

·  For stroke or cerebro vascular disorders – prevention of recurrent episodes.

·  For transient ischemic attacks – prevention of progression to stroke.

·  Prevention of pregnancy induced hypertension and eclampsia.

·  Following arterial bypass to prevent restenosis.

·  In arterial and venous disorders, such as TAO to reduce inflammation and to increase blood flow to the supplied area.

For analgesic and antipyretic Indications : 300-900 mg 6th hourly, upto a maximum of 4

60 mg/kg/day for children.

For antiplatelet effect : 75-150 mg o.d

Routes of Administration   Oral

 

Contraindications

·  Active petic ulcer disease.

·  Haemophilia and other haemorrhagic disorders, anticoagulant treatment.

·  Apart from low dose aspirin regimes, it should not be used in pregnancy.

·  Should not be used in lactating mothers and children under one year of age.

·  In treatment of viral haemorrhagic fevers such as dengue.

·  Hypersensitive patients, in whom history of bronchial asthma, angioedema or urticaria have been precipitated by aspirin or other NSAIDS.

Precautions / Practice points

·  Alcohol increases the GI adverse effects and hence instruct patients to abstain from alcohol.

·  Use with caution in patients with hepatic or renal dysfunction and in elderly – increased risk of side effects.

·  Use with caution in children below 12 years except for the treatment of juvenile rheumctoid arthritis. Aspirin should not be used for any other minor illnesses.

·  Look out for tinnitus as an early indicator of toxic symptoms and withdraw the drug immediately.

·  It is not advisable to take one more NSAID if the patient is already on aspirin – such combinations are more at risk for developing analgesic nephropathy.

·  Stop aspirin 7 days before any planned surgery.

·  While on long term therapy monitor renal, hepatic parameters and for signs of gastro-intestinal bleeding.

·  Aspirin may give false negative results in testing for urine sugar by glucose oxidase strips.

·  Administration Instructions:

-  Administer along with food to reduce gastro-intestinal side effects.

-  Instruct patients to report immediately if ringing in ears or any bleeding tendencies

like bleeding from gums or persistent abdominal pain occurs.  Withdraw the drug immediately.

-  Open package immediately before use.

-  Do not administer aspirin exposed to water or air for a long time

Drug Interactions

Potentially fatal:

·  With anti coagulants such as warfarin – major bleeding episode may occur due to inhibition of platelet aggregation.

·  Increases methotrexate levels and may precipitate toxicity.

Non fatal

·  Enhaunces effects of phenytoin, valproate.

·  Increases risk of gastro-intestinal bleeds with steroids.

·  May antagonize diuretic effects of spirinolactone.

·  Metaclopramide increases absorption and hence, effects of aspirin.

Adverse Effects

Usually occurs at doses of more than 1 gm/day.

Common effects:

·  GIT  - stomach pain, heart burn, nausea, vomiting, epigastric discomfort, ulceration.

·  Effects on hearing – tinnitus (very common), vertigo, mild hearing loss.

Rare effects:

·  Hypersensitivity – angioedema, skin eruptions, paroxysmal bronchospasm.

·  Haematological – iron deficiency anaemia, prolongation of bleeding time, may cause haemolytic anaemia in G6PD deficiency patients.

·  Liver – hepatotoxicity (usually reversible).

·  Kidney – Analgesic nephropathy – especially if combinations of NSAIDS are used.

·  Reye’s syndroe – acute encephalopathy and hepatic injury in children, when used for  antipyretic effects in viral infections such as flu or chicken pok.

Drug Toxicity (SALICYLISM)

Toxic doses  - 150-175 mg/kg.

Symptoms – headache, dizziness, tinnitus, vertigo, mental confusion, restlessness, marked alteration in acid base balance, acidosis, sweating, dehydration, hyperpyrexia, nausea, vomiting, hyperventilation, coma followed by cardiovascular collapse and respiratory arrest due to its CNS depressant activity.

Treatment of Toxicity

·  Gastric lavage, activated charcoal or emesis to remove unabsorbed poison.

·  Ice packs and external cooling measures to reverse hyperthermia.

·  Maintain urinary output, fluid and electrolyte imbalance with adequate I.V. fluids.

·  Alkalinization of urine can be done to increase the excretion, by giving IV sodium bicarbonate.

·  Cardiovascular and respiratory support.

·  Vitamin K, fresh blood – if bleeding is prominent.

·  Haemodialysis – if severe poisoning and serum levels are above 700 mg/litre.

Storage

Store in airtight containers,  in a cool place.

Shelf Life                    18 months.

                                                     PARACETAMOL

General   Information

Drug Code                        Preparation                                             Strength

            2                      Tab. Paracetamol                                       500 mg

            3                      Syr. Paracetamol                                        60 ml (125 mg/5ml)

         249                     Paracetamol Oral solution                        15 ml (150 mg/ml)

         351                     Inj. Paracetamol                                        2 ml / Amp (150 mg/ml)          

Description of the Drug

Paracetamol is a non-narcotic nonsalicylate analgesic. Unlike other NSAIDS, it has little or no anti-inflammatory activity.

Mode of Action

It acts by inhibiting prostaglandin synthesis in the CNS (hence acting as antipyretic and analgesic).  It has weak anti inflammatory activity in the peripheral tissues and does not inhibit platelet aggregation.

Pharmacokinetics

It is readily absorbed from the upper GIT. Onset of action is 30 minutes after ingestion.  Duration of effects is 2-5 hours. It is metabolized predominantly in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates.

Clinical  Information 

Indications

Pain relief:

·  Minor aches and pains, associated with colds and other infections.

·  Postpartum pain.

·  Headache.

·  Dental pain.

·  Myalgia.

·  Dysmenorrhoea.

Pyrexia:

·  For reducing fever of any cause – infective etc.,

Dosage

Adults

            0.5-1 gm, every 4-6 hours upto a maximum of 4 gms.

Children

            10 mg/kg, every 4-6 hours.

Routes of Administration   Oral, Parenteral (I.M.). Never  I.V.

Contraindications

            Patients who are hypersensitive to paracetamol.

Precautions / Practice points

·  Use with great caution in patients with hepatic dysfunction and in alcoholics.

·  It is preferable to aspirin in the following patient groups:

Patients with acid peptic disease.

Patients with bleeding disorders and haemophiliacs.

Children with viral infections.

Patients  in whom bronchospasm is precipitated by aspirin.

Infants less than 6 months of age..

·  Safe in pregnancy and lactation.

·  Administration instructions:

-     Administration with food.

-     Do not give intravenously.

-     Instruct patients not to drink alcohol.

Drug Interactions

No fatal interactions have been reported.

·  Rifampicin may reduce the efficancy of paracetamol.

·  Paracetamol increases the serum levels of chloramphenicol when administered together.

·  Paracetamol may potentiate the toxicity of zidovudine and warfarin sodium.

Adverse Effects:

Rare in usual doses.  There may be:

·  Hypersensitivity to the drug – urticaria, dyspnoea, hypotension, angioedema, fixed drug eruptions.

·  Elevation of liver enzymes and hepatic dysfunction in large doses (more than 5 to 8 gms, over several weeks).

·  Interstitial nephritis, papillary necrosis when used in combination with other analgesics.

·  Haemolytic anemia, methaemoglobinemia, thrombocytopenia, leucopenia may occur.

Drug Toxicity

·  Toxic doses  for adults : More than 10-15 gm or more than 20 tablets.

·  For children more than 150 mg/kg.

·  Initially causes dizziness, disorientation, abdominal pain, nausea, vomiting, diaphoresis, general malaise.  Later, fatal hepatic necrosis, renal tubular necrosis and coma may occur.

Treatment of Toxicity

·  Gastric lavage.

·  Emetics to induce vomiting to decrease absorption.

·  Antidote:

·  N-acetylcysteine ( when overdose of paracetamol is more than 150 mg/kg).

Initial  bolus dose of 150 mg/kg in 5% dextrose given over 15-60 min.

Maintenance dose is 50 mg/kg every 4 hours.

Monitor serum levels of enzymes of liver function  - SGOT, SGPT, etc.

Storage

·  Store in airtight container.

·  Protect from light.

·  Cool dry place.

Shelf Life                    2 years.

                                                                        IBUPROFEN

General   Information

Drug Code                    Preparation                                             Strength

114                    Tab. Ibuprofen                                             200 mg-100 Tabs.

            255                    Tab. Ibuprofen                                             400 mg          

Description of the Drug

Ibuprofen is a non-steriodal anti-inflamatory agent of the propionic acid group, possessing anti-inflammatory, analgesic and antipyretic activity.

Mode of Action

It is a reversible inhibitor of the cyclo-oxygenase enzyme. Thus, it inhibits the synthesis of prostaglandins, and not that of leukotrienes.

Pharmacokinetics

It is readily absorbed from the GIT. It is extensively bound to plasma proteins and is excreted in the urine mainly as metabolites and their conjugates. Onset of analgesia is 30-60 min after ingestion.  Duration of action is 6-8 hours.

Clinical  Information

Indications

·  Short term analgesia in minor aches and pain due to colds, flu, sore throat, headache, dental pain, dysmenorrhoea etc.

·  For relief of pain and inflammation, osteo arthritis and other chronic inflammatory disorders.

Dosage

For short term analgesic effects:

Adults     - 400 mg 4-6 hours.

Children  - 10mg/kg – 8 hourly – 6-12 years.

For chronic inflammatory disorders:

            Adult       - 1.2 – 1.8 gm in 4 divided doses upto a maximum of 2.4 gm/day.

            Children  - 20-40 mg/kg in 3, 4 divided doses.

Individualization of dose is necessary, starting from lower most dose possible, gradually increasing till clinical response is satisfactory.

Routes of Administration   Oral, Parenteral (I.M.). Never  I.V.

Contraindications

·  Contraindicated in pregnancy and children less than 6 months.

·  Do not administer in case of active gastro-duodenal ulcer disease or liver failure.

·  Individuals in whom angioedenia and bronchospasm have been precipated by NSAIDS like aspirin.

Precautions / Practice points

·  Use with  caution in elderly.  Avoid in children less than 7 kg, in bleeding disorders and patients on oral anticoagulants.

·  Use with caution in hepatic dysfunction and congestive cardiac failure.

·  In renal impairment, ibuprofen can reduce renal blood flow (by inhibition of prostaglandin mediated renal vaso dilation) and can precipitate renal failure.

·  On long term therapy, monitor hepatic and renal parameters and signs of gastro-intestinal bleeding.

Drug Interactions

Potentially fatal:

·  Increases the effects of oral anticoagulants and risk of bleeding episodes.

·  Increases the toxicity of methotrexate, lithium and digoxin by reducing their excretion.

Non fatal:

·  Antagonises hypotensive action of ACE inhibitors and increases risk of renal damage when used together.

·  Increases renal toxicity of cyclosporin.

Adverse Effects

Common effects:

·  GIT – abdominal discomfort, nausea, vomiting, abdominal pain or activation of peptic ulcer.

Rare effects:

·  Dizziness, headache, tinnitus, depression.

·  Hypersensitivity reactions – fever and rashes, Steven-Johnson’s syndrome, toxic epidermonecrolysis may occur.

·  Fluid retention and hepatotoxicity.

·  Haematological – agranulocytosis, aplastic anaemia, haemolytic anaemia,reversible, inhibition of platelet aggregation.

Drug Toxicity

Toxic doses  - more than 200 mg/kg.  Abdominal pain, nausea, vomiting, drowsiness, CVS toxicity like hypotension, arrhythmias and bradycardia.  May progress to metabolic acidosis, apnoea and acute renal failure and coma.

Treatment of Toxicity

·  Gastric lavage and emesis, if ingested within half an hour, administration of activated charcoal for prevention, of absorption.

·  symptomatic and supportive line of management – treat GI bleed, hypotension and metabolic acidosis if present.

Storage

Store in cool dry place.

Shelf Life                    3 years.

PETHIDINE

General   Information

Drug Code                        Preparation                                       Strength

156                  Inj.Pethidine HCI                                        50 mg/ml.

Description of the Drug

Pethidine is a opioid analgesic with some antimuscarinic effects.

Mode of Action

Similar to morphine, pethidine acts on the opioid receptors to cause analgesia and sedation.  Besides, it also acts as an antagonist at the cholinergic rocepton to produce atropine like effects.

Pharmacokinetics

After IM adminstration, onset of action is within 10-15 min; given intravenously, onset of action is within 5 minutes.  Duration of effects is 3-4 hours. Metabolized in the liver to active metabolites and excreted in urine.  It crosses the placenta and appears in breastmilk.

Clinical  Information 

Indications

·  Used in pre operative medication as an adjuvant to anaesthesia – for sedative and anxiolytic effects.

·  Relief of moderate to severe pain of any cause.

·  Obstetrical analgesia.

Dosage

·  As an analgesic : 25 –100 mg, 4th hourly, dose to be adjusted according to requirements.

·  For preoperative medication : 50-100 mg, 30-90 minutes before surgery.

·  Obstetric analgesia : 50-100 mg, as soon as pain starts, repeated at 1-3 hourly intervals, upto a maximum of 400 mg/day.

Routes of Administration    IM, IV, SC.

Contraindications

·  In patients receiving MAO inhibiton presently or within the past 2 weeks.

·  In acute alcoholism, head injuries, states of preexisting CNS depression and conditions in which increased intracranial tension occurs.

·  Hypersensitivity.

·  Severe renal failure.

Precautions / Practice points

·  Should be given cautiously to patients with supraventricular tachycardia or with history of convulsive disorders.

·  Being an opioid, the drug has an abuse potential and can be addictive.

·  Use with caution in conditions like bronchial asthma, COPD, states with reduced respiratory reserve, because it is a respiratory depressant.

·  Instruct patients not to drive or operate machinery as it causes sedation and drowsiness.

·  Can cause respiratory depression in newborn.  Judicious use is necessary in obstetrical analgesia.

·  Not suitable for chronic use as, cumulative toxicity with its active metabolite (non pethidine) could result.

·  Adminstration Instruction:

-     Incompatible with aminophylline, barbiturates, heparin, phenytoin and sodium bicarbonate and should not be mixed or given in the same syringes.

-     IM adminstration is preferred. If given intravenously, a solution of concentration 10 mg/ml should be used and given very slowly.  Rapid IV adminstration may result in hypotension, apnoea and collapse.

Drug Interactions

Potentially fatal:

·  Very severe reactions including coma, severe respiratory depression, cyanosis and hypotension similar to narcotic overdose have occurred in patients receiving MAO inhibitors and pethidine concomitantly.  Hence, patients should not be given this drug when they are receivig MAO inhibitors or within 14 days of discontinuation of the drug.

Non fatal:

·  Concurrent administration of pethidine with phenothiaziness and tricyclic antidepressants potentiates the effect of pethidine and dose is to be reduced by 50-25%.

·  Barbiturates, sedative hypnotics, opioids, alcohols, tricyclic antidepressants given along with pethidine may cause excessive CNS depression.

·  Hepatic metabolism of pethidine is enhanced by phenytoin which therefore reduces analgesic effects of pethidine.

Adverse Effects

Common effects:

·  Local pain at injection site.

·  Sedation, nausea, lightheadedness, vomitting.

Rare effects:

·  CNS effects -  euphoria, mood changes, agitation, tremor, muscle twitching, disorientation, hallucination.

·  Dependency and drug abuse.

·  CVS – tachycardia, hypertension.

·  Constipation.

Drug Toxicity

Respiratory depression, apnoea, mydriasis ( unlike other opoids), extreme somnolence, muscle flaccidity, cold extremities, cold clammy skin, hypotension, cardiovascular depression like bradycardia, stupor, coma and death.

Treatment of Toxicity

·  Maintenance of airway, supportive ventilation, oxygen, IV fluids and vasopressors for maintenance of blood pressure.

·  Antidote : Nalozone can be given.

Storage

Protect from light.

Shelf Life                    2 years.

                                               PENTAZOCINE LACTATE

General   Information

Drug Code                        Preparation                                          Strength

         157                        Inj.Pentazocine lactate                               30 mg/ml.           

Description of the Drug

Pentazocine is a benzomorphane derivative.  It is an opioid analgesic.

Mode of Action

The drug has mixed activity. I.e. both agonist and antagonist actions.  Agonist activity is thought to be predominantly at kappa receptors.  It acts as a weak antagonist or partial agonist at Mu receptors in the CNS, acting as a CNS depressant.

Pharmacokinetics

When administered IM or SC, onset of analgesic action is 15 minutes after adminstration.  After IV injection, onset of action is 2-3 min. Duration of action is 2-3 hours.  Pentazocine undergoes metabolism in the liver, to glucoronide conjugates and is excreted in the bile.  Small amounts are excreted in the urine.

Clinical  Information 

Indications

Relief of moderate to severe pain, in postoperative period in bony metastates in cancer patients etc.,

Dosage

Adults:

            30-60 mg every 4-6 hours.

Children:

            500 mcg/kg upto 1 mg/kg/dose.

Routes of Administration    IM, IV, SC.

Contraindications

·  In the post myocardial infarction period as it increases cardiac work load.

·  In acute alcoholism, head injuries and conditions in which increased intra cranial pressure occurs. (Pentazocine causes respiratory depression and carbondioxide retention, increasing CSF pressure).

·  Patients hypersensitive to pentazocine.

Precautions / Practice points

·  Use with caution in bronchial asthma, chronic lung diseases, where respiratory reserve is decreased because of its respiratory depressant effects.

·  Avoid antihupertensives and cardiac disorders, in patients with heart failure as it causes rise in B.P. and causes tachycardia.

·  For dose adjustments in liver and kidney failure see appendix.

·  Use with caution after biliary surgery, since opioids increase biliary tract pressure by constriction of sphincter of oddi.

·  Warn chronic users not to drive or operate machinery.

·  Administration Instructions:

-     Pentazocine is incompatible with aminophylline, barbiturates and heparin and should not be mixed or given in the same heparin and should not be mixed or given in the same syringe.

Drug Interactions

Non fatal:

·  Weakly antagonizes the effects of other opiod analgesics.

·  Therefore, addicts and patients on other opioid analgesics may have withdrawal symptoms.

·  Produces incomplete reversal of CVS and respiratory system depression induced by morphine.

·  Alcohol and other CNS depressants may cause excessive CNS depression.

Adverse Effects

Common effects:

·  Drowsiness, light headedness or euphoria.

·  Nausea, vomiting.

Rare effects:

·  Visual hallucinations, dizziness, disorientation, confusion, headache, visual blurring, nightmares.

·  Palpitations, hypotension.

·  Drug abuse.

Drug Toxicity

Drowsiness, sedation, respiratory depression and coma.

Treatment of Toxicity

·    Monitoring of CVS, respiratory status, supportive ventilation. Naloxone hydrochloride is given as specific antidote in the dose of 0.4-2 mg by IV. Repeated at the intervals of 2-3 minutes, upto a total of 10 mg.

Storage

Protect from sunlight.

Shelf Life                    4 years.

                                            DICLOFENAC SODIUM

General   Information

Drug Code                        Preparation                                             Strength

         251                         Tab. Diclofenac Sodium                           SR  100 mg/ml.

         252                         Tab. Diclofenac Sodium                           50 mg/ml.

         495                         Inj.  Diclofenac Sodium                            25 mg/ml – 3 ml Amp.

Description of the Drug

Diclofenac is a non-steroidal anti-inflammatory agent with anti-inflammatory, antipyretic activities used for a variety of painful and inflammatory conditions.

Mode of Action

It is a cyclo-oxygenase inhibitor. Its anti-inflammatory property is due to decreased prostaglandin synthesis in the tissues.

Pharmacokinetics

On oral administration, completely absorbed in a fasting state.  It is subject to first-pass metabolism and only 50% is bioavailable.  Onset of action is 10 minutes. Duration is 8 hours.  It penetrates the synovial fluid and is detected in breast milk.  Excreted in the form of glucoronide and sulphate conjugates, mainly in the urine but also in the bile.

Clinical  Information

Indications

·  Acute or short term analgesia :

-     Postoperative analgesia.

-     Abdominal and renal colic.

-     Dental extraction.

-     Dysmenorrhoea, abdominal and renal colic.

·  In localized soft-tissue inflammatory lesions following trauma to tendons, ligaments, muscles and joints, acute attacks of gout.

·  Long term use in musculo skeletal disorders like rheumatoid arthritis, juvenile rheumatoid arthritis, osteo arthritis, ankylosing spondylitis.

Dosage

Adults:    usual : 50 mg 2-3 times a day.

For dysmenorrhoea : 100 mg initially followed by 50 mg after 8 hours if required.

For chronic inflammatory disorders : 150-200 mg in 2,3 divided doses or 100 mg/day of SR Preparation.

Children:

            Orally : 1-3 mg/kg body WEIGHT/day in divided doses.

Parenteral

I.M. : 75 mg once or twice daily depending on requirements.

Routes of Administration    IM, IV, SC.

Contraindications

·  Active peptic ulcer.

·  Bleeding disorders and patients on anticoagulant, therapy.

·  History of hypersensitivity reactions to other NSAIDS.

·  Porphyria.

Precautions / Practice points

·  Warn chronic users about symptoms of liver toxicity like nausea, fatigue, lethargy, pruritis, right hypochondrial pain, flu like symptoms.

·  Use with caution in patients with compromised renal, hepatic orcardiacfailure; renal failure can be precipitated Due to reduction of renal blood flow.

·  Monitor blood counts, hepatic and renal parameters periodically in patients on long term therapy.

·  Administration Instructions:

-     Take with food to reduce GI effects.

Drug Interactions

Potentially  fatal:

·  Oral anticoagulants, corticosteriods, other NSAID’s like aspirin increases the risk of peptic ulcer bleeding.

·  Lithium, digoxin and methotrexate blood levels will be raised when given with diclofenac.  Therefore, diclofenac increases risk of toxicity due to these drugs.

·  Increases nephrotoxicity of cyclosporin.  If used together, halve the dose of diclofenac.

Non fatal:

·  May decrease effects of thiazide and furosemide.

Adverse Effects

Common effects:

·  Epigastric pain, bleeding from ulcers and perforation.  Old debilitated patients, smokers, alcoholic patients are especially at risk for GI side effects.

Rare effects:

·  Hepatic enzymes like SGOT, SGPT may be elevated, especially in chronic users, rarely acute fulminant hepatitis can occur.  Therefore, periodic monitoring of liver function tests to be done in chronic users.

·  Fluid retention and edema.

·  Precipitation of asthmatic attacks in susceptible individuals.

·  Haematological – anaemia due to either gastro-intestinal bleeding or fluid retention, inhibition of platelet aggregation, increase in bleeding time.

·  Rashes, pruritis, bullous dermatitis and erythema multiforme.

Drug Toxicity

Drowsiness, CNS depression and acute renal failure.

Treatment of Toxicity

·  Reduce absorption by vomiting, lavage, activated charcoal.

·  Forced diuresis.

·  Symptomatic treatment – monitor electrolyte and fluid balance.

Storage

Store in a cool, dry, dark place.

Shelf Life                    3 years.

INDOMETHACIN

General   Information

Drug Code                      Preparation                                         Strength

         254                         Cap. Indomethacin                       25 mg.        

Description of the Drug

Indomethacin is an NSAID with anti-inflammatory, antipyretic, analgesic properties.

Mode of Action

It is a highly potent inhibitor of prostaglandin synthesis in peripheral tissues.  Apart from its anti-inflammatory Indications, it may be used in medical closure of P.D.A.( as an I.V. Preparation).

Pharmacokinetics

Well absorbed orally.  Onset of action is 30 min after ingestion.  Duration of effects is for 4-6 hrs.  Metabolized in the liver and excreted in the urine as gluconoride conjugates. 

Clinical  Information

Indications

Short term use:

·  Acute gouty arthritis.

·  Musculoskeletal injuries, bursitis etc.,

Long term use:

·  Anti-inflammatory agent in musculoskeletal disorders like rheumatoid arthritis, ankylosing spondylitis and osteo arthritis.

Dosage

Adult

·  For musculoskeletal disorders: 25-30 mg two or three times daily,upto 150-200 mg daily.

·  In acute gouty arthritis: 50 mg thrice daily.

Children

·  Not recommended.

Routes of Administration    IM, IV, SC.

Contraindications

·  Patients hypersensitive to other NSAIDS and asthmatics, in whom bronchospasm may be precipitated.

·  Patients with acid peptic disease – either active disease or with previous history.

·  Third trimester of pregnancy – may cause premature closure of PDA.

·  Impaired renal function.

·  Bleeding disorders and patients on anticoagulants.

Precautions / Practice points

·  Avoid in children – risk of side effects such as hepatotoxicity are higher; if used, liver function tests must be monitored frequently.

·  May cause fluid retention, hence, use with caution in congestive cardiac failure.

·  Use with caution in elderly – a reduction of dose is advised.

·  Administration Instructions:

-  Take with food.

Drug Interactions

Potentially  fatal:

·  May cause major bleeding episodes if given with anticoagulants.

·  Increases the serum levels of the drugs like lithium, methotrexate, digoxin and

May precipitate their toxic side effects.

Non fatal:

·  Concurrent administration of other NSAIDS increases GI and renal toxicity.

·  It blunts the diuretic action of furosemide and thiazides.

·  It decreases the antihypertensive effects of thiazides, furosemide, beta blockers and ACE inhibitors.

·  Increases nephrotoxicity of cyclosporin.

Adverse Effects

Common effects:

·  Gastro intestinal disturbance – initially dyspepsia, nausea, etc, may progress to marked gastric irritation, gastric bleeding and diarrhoea, ulcers, perforation of ulcers may occur.

Rare effects:

·  Headache, dizziness, vertigo, somnolence, depression, psychiatric disturbances.

·  Hypersensitivity reactions – bronchospasm, urticaria, skin eruptions, Steven Johnson’s syndrome.

·  Fluid retention and edema.

·  Ocular – retinal, macular and corneal deposits, with blurring of vision.

·  Thrombocytopenia.

Drug Toxicity

Nausea, vomiting, intense heachache, confusion, tinnitus, disorientation, renal failure, GI bleeding, rarely paraesthesia and convulsions.

Treatment of Toxicity

·  Gastric lavage and emesis, activated charcoal.

·  Symptomatic treatment – under close medical supervision.

·  Diazepam to manage convulsions.

Storage

Store in airtight containers. Protect from light.

Shelf Life                    3 years.