Isoniazid BP 100mg/tablet
White 3/8" normal convex tablet.
Treatment of pulmonary and extrapulmonary tuberculosis in combination with other antitubercular agents.
Recommended Isoniazid doses are 4 to 5 mg per kg body-weight in divided doses up to a maximum of 300 mg daily or up to 10 mg per kg body-weight may be given for the first 1 - 2 weeks of treatment for tuberculous meningitis.
Doses of Isoniazid for children are 5 to 20 mg per kg body-weight daily. Intermittent administration is used to improve compliance and reduce toxicity. Regimens in which Isoniazid is given two or three times weekly are effective, but once weekly administration is not clinically effective in rapid acetylators. Standard doses of Isoniazid may be given to patients with renal impairment; although those on dialysis should receive Isoniazid following the procedure as the drug is removed by dialysis. The dose may need to be reduced in patients with liver impairment.
Patients who develop severe hypersensitivity reactions including drug induced hepatitis; Previous isoniazid associated hepatic injury; Severe adverse reactions to isoniazid, such as drug fever, chills and arthritis. Acute hepatic disease of any aetiology; and Patients with known hypersensitivity to isoniazid or any of the excipients listed under FURTHER INFORMATION.
Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is age-related. Approximate case rates by age are: 0/1,000 for people under 20 years of age; 3/1,000 for people in the 20 to 34 year age group; 12/1,000 for people in the 35 to 49 year age group; 23/1,000 for people in the 50 to 64 year age group; and 8/1,000 for people in the over 65 year age group. The risk of hepatitis is increased with daily consumption of alcohol. Precise data to provide a fatality rate for isoniazid related hepatitis are not available. However, in a US Public Health Service Surveillance Study of 13,838 people taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Therefore, patients taking isoniazid should be carefully monitored and interviewed at monthly intervals. Serum transaminase concentration becomes elevated in about 10 - 20% of patients, usually during the first few months of therapy, but it can occur at any time. Usually, enzyme levels return to normal despite continuance of the drug, but in some cases, progressive hepatic dysfunction occurs. Patients should be instructed to report immediately any of the prodromal symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly, since continued use of the drug in these cases has been reported to cause a more severe form of hepatic damage. Patients with tuberculosis should be given appropriate treatment with alternative drugs. If isoniazid must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent hepatic involvement. Preventive treatment should be deferred in people with acute hepatic diseases. All drugs should be stopped and an evaluation made at the first sign of a hypersensitivity reaction. If isoniazid therapy must be reinstituted, the drug should be given only after symptoms have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is a recurrent hypersensitivity reaction. Use of isoniazid should be carefully monitored in patients who are receiving phenytoin or carbamazepine concurrently and in patients who are daily users of alcohol (see INTERACTIONS).
Optic neuritis and atrophy have been reported with isoniazid. Ophthalmological examinations (including ophthalmoscopy) should be done before starting isoniazid and periodically thereafter, even without the occurrence of visual symptoms.
Isoniazid should be carefully monitored in patients with current chronic hepatic disease.
It has been reported that, in both rats and rabbits, isoniazid may exert an embryocidal effect when administered orally during pregnancy, although no isoniazid-related congenital anomalies have been found in reproduction studies in mammalian species (mice, rats and rabbits). Isoniazid should be prescribed during pregnancy only when therapeutically necessary. The benefit of preventive therapy should be weighed against a possible risk to the foetus. Preventive treatment should be started after delivery because of the increased risk of tuberculosis for new mothers.
Since isoniazid is known to cross the placental barrier and to pass into maternal breast milk, neonates and breast-fed infants of mothers treated with isoniazid should be carefully observed for any evidence of adverse effects.
Studies conducted with children have illustrated no paediatric-specific problems limiting the use of isoniazid in children. However, new-born infants have limited acetylation capacity, which results in prolonged elimination half-life of isoniazid.
Patients over 50 years of age have the highest incidence of hepatitis (see Adverse Effects).
Isoniazid has been reported to induce pulmonary tumours in a number of strains of mice. However, isoniazid has not been shown to be carcinogenic or tumorgenic in humans.
Isoniazid has been reported to cause false-positive results with cupric sulfate solution (Benedict's reagent and Clinitest) for urine glucose determinations.
The use of isoniazid should be carefully monitored in patients who are receiving phenytoin concurrently as it may decrease the excretion of phenytoin or may enhance its effects. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made.
Concurrent use of carbamazepine with isoniazid increases serum carbamazepine levels and toxicity. It can also lead to degradation of the isoniazid to hepatotoxic metabolites.
Daily ingestion of alcohol may be associated with a higher incidence of isoniazid hepatitis.
Increase hepatotoxicity may occur due to possible alteration of isoniazid metabolism.
Isoniazid is thought to induce cytochrome P450 that results in an increased proportion of paracetamol being converted to toxic metabolites.
Nervous System
Peripheral neuropathy is the most common side effect of isoniazid and occurs most often in "slow-acetylators", uremics, malnourished patients, alcoholics and diabetics. Peripheral neuropathy is dose related and is uncommon with doses of isoniazid less than 5mg/kg. Patients receiving larger than usual doses or with pre-existing peripheral neuritis should receive 100mg to 300mg of pyridoxine daily. Other side effects include: Convulsions Toxic encephalopathy Optic neuritis Atrophy Memory impairment Toxic psychosis Fatigue Malaise Weakness
Gastrointestinal
Nausea Vomiting Epigastric distress Anorexia
Hepatic
Elevated serum transaminases (AST, ALT) Mild and transient elevation of serum transaminase levels occurs in 10 - 20% of people taking isoniazid. The abnormality usually occurs in the first 4 - 6 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal with no necessity to discontinue medication. In occasional instances, progressive hepatic damage occurs, with accompanying symptoms. In these cases, the drug should be discontinued immediately. The frequency of progressive hepatic damage increases with age. It is rare in people under 20 years but occurs in up to 2.3% of those over 50 years of age. Bilirubinaemia Bilirubinuria Jaundice Severe and sometimes fatal hepatitis
Haematological
Agranulocytosis Haemolytic Sideroblastic or aplastic anaemia Thrombocytopenia Eosinophilia
Hypersensitivity
Fever Skin eruptions (morbilliform, maculopapular, purpuric or exfoliative) Lymphadenopathy Vasculitis
Metabolic and endocrine
Pyridoxine deficiency Pellagra Hyperglycaemia Metabolic acidosis Gynaecomastia
Systemic
Rheumatic syndrome Systemic lupus erythematosus-like syndrome.
Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting, dizziness, slurring of speech, blurring of vision and visual hallucinations (including bright colours and strange designs) are among the early manifestations With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, are to be expected, along with severe intractable seizures. Severe metabolic acidosis, acetonuria and hyperglycaemia are typical laboratory findings.
Untreated or inadequately treated cases of gross isoniazid overdosage can terminate fatally, but good response has been reported in most patients brought under adequate treatment within the first few hours after drug ingestion. Secure the airway and establish adequate respiratory exchange. Gastric lavage within the first 2 - 3 hours is advised, but should not be attempted until convulsions are under control. To control convulsions, administer intravenous short-acting barbiturates and intravenous pyridoxine (usually 1mg/1mg isoniazid ingested). Obtain blood samples for immediate determination of gases, electrolytes, serum urea, glucose, etc. Type and cross-match blood in preparation for possible haemodialysis. Rapid control of metabolic acidosis is fundamental to management. Give intravenous sodium bicarbonate at once and repeat as needed, adjusting subsequent dosage on the basis of laboratory findings (i.e. serum sodium, pH, etc.) Forced osmotic diuresis must be started early and should be continued from some hours after clinical improvement to hasten renal clearance of the drug and help prevent relapse. Monitor fluid intake and output. Haemodialysis is advised for severe cases. If this in not available, peritoneal dialysis can be used along with forced diruesis. Along with measures based on initial and repeated determination of blood gases and on other laboratory tests as needed, utilize meticulous respiratory and other intensive care to protect against hypoxia, hypotension, aspiration pneumonitis, etc.
Isoniazid is tuberculostatic agent. It has antibacterial activity only against mycobacteria. It has bacteriostatic activity against Mycobacterium tuberculosis and is one of the first line chemotherapeutic agents used in treating tuberculosis. Because resistance develops with a few weeks to isoniazid used alone, it is given together with one or more of the other antitubercular agents.
Absorption
Isoniazid is readily and completely absorbed when given orally and produces peak blood levels within 1 - 2 hours which decline to 50% or less within 6 hours. When administered orally with food, the extent of absorption and peak plasma concentrations of the drug may be reduced.
Distribution
Isoniazid is distributed into all tissues and fluids. CSF concentrations of the drug are reported to be 90 - 100% of concurrent plasma concentrations. Isoniazid is not substantially bound to plasma proteins. It readily crosses the placenta and is distributed into milk in concentrations equal to maternal plasma concentrations.
Elimination
The plasma half-life of isoniazid in patients with normal renal and hepatic function ranges from 1 - 4 hours, depending on the rate of metabolism. The plasma half-life may be prolonged in patients with impaired hepatic function or severe renal impairment. Isoniazid is metabolised primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50% of Africans and Caucasians are "slow inactivators"; the majority of Eskimos and Asians are "rapid inactivators". The rate of acetylation does not significantly alter the effectiveness of isoniazid. However, slow acetylation may lead to higher blood levels of the drug, and thus an increase in toxic reactions. From 50 - 70 % of a dose of isoniazid is excreted in the urine in 24 hours. Pyridoxine deficiency (B6) is sometimes observed in adults with high doses of isoniazid and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.
Lactose monohydrate, wheat starch, magnesium stearate, purified water
Store below 25deg C.
Glass bottles of 100 tablets.
Prescription Medicine
PSM Healthcare Ltd trading as API Consumer Brands PO Box 76 401 Manukau City Auckland
8th July 2011