INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo RIFINAH® -150 TABLETS
RIFINAH® -300 TABLETS

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

RIFINAH® -150 TABLETS
RIFINAH
® -300 TABLETS

COMPOSITION:
RIFINAH-150 contains 150 mg
rifampicin and 100 mg isoniazid and RIFINAH-300 contains 300 mg rifampicin and 150 mg isoniazid.

PHARMACOLOGICAL CLASSIFICATION:
A 20.2.3 Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION:
Rifampicin is an antibiotic with bactericidal activity against M. tuberculosis. It has the ability to kill intracellular and extracellular micro-organisms.
Rifampicin is about 89% protein bound and has a half-life of 2 - 5 hours.
Isoniazid is bacteriostatic for resting bacilli, but is bactericidal for rapidly dividing organisms. Isoniazid is not bound appreciably to plasma proteins.

INDICATIONS:
RIFINAH is indicated for the treatment of all forms of tuberculosis, including fresh, advanced and chronic cases.

CONTRA-INDICATIONS:
RIFINAH is contra-indicated in jaundice, acute porphyria and in patients with a history of hypersensitivity to rifamycins or isoniazid. Rifampicin ran cause thrombocytopenia and purpura, usually with intermittent tuberculosis regimens, further administration is contra-indicated.
Use in pregnancy and lactation:
Rifampicin and isoniazid have been reported to cross the placental barrier and a appear in cord blood. RIFINAH should be used in pregnant women or in women of childbearing potential only if the potential benefit justifies the potential risk to the foetus. During the first trimester of pregnancy, RIFINAH must only be used in life-threatening conditions and where no other suitable alternative treatment is available. Rifampicin has been shown to be teratogenic in rodents when given in large doses. Isoniazid has been reported to exert an embryocidal effect in both rats and rabbits.
When administered during the last few weeks of pregnancy rifampicin has caused post-natal haemorrhages in the mother and infant, for which treatment with vitamin K
1 may be indicated. Rifampicin and isoniazid are excreted in breast milk. Safety in lactation has not been established.

WARNINGS:
RIFINAH is a combination of two drugs, each of which has been associated with liver dysfunction. Patients with current chronic liver disease, impaired liver function or severe renal dysfunction should only be given RIFINAH in cases of necessity and then with caution and under strict medical supervision. In these patients careful monitoring of liver function, especially serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT), should be carried out prior to therapy and then every two to four weeks during therapy.
Severe and sometimes fatal hepatitis may occur with RIFINAH. The risk of developing hepatitis is age related. Therefore, patients should be monitored for the prodromal symptoms of hepatitis such as fatigue, weakness, malaise, anorexia, nausea or vomiting. If signs of hepatocellular damage occur, RIFINAH should be withdrawn immediately.
In some cases hyperbilirubinaemia can occur in the early days of treatment. The decision to interrupt treatment should be made after evaluating the patient's clinical condition in conjunction with repeated liver function tests. Possible immunological reactions including anaphylaxis may occur with intermittent therapy. Patients should be cautioned against interruption of dosage regimens.
Patients who are at risk of neuropathy or pyridoxine deficiency including those who are diabetic, alcoholic, elderly, malnourished, uraemic or pregnant should receive pyridoxine usually in a dose of 10 mg daily.
Contraception: To preclude all possibility of pregnancy during treatment with RIFINAH, women of childbearing potential must employ adequate non-hormonal means of contraception.

DOSAGE AND DIRECTIONS FOR USE
Other antituberculosis agents may be given concurrently until the susceptibility of the infecting organism to rifampicin and isoniazid has been confirmed. Adult patients should be given the following daily dose at least 30 minutes before a meal or 2 hours after a meal:
RIFINAH-150: Patients weighing less than 50 kg: 3 tablets (450 mg rifampicin and 300 mg isoniazid).
RIFINAH-300: Patients weighing 50 kg or greater: 2 tablets (600 mg rifampicin and 300 mg isoniazid).
The choice of either the 450 mg or 600 mg dose of rifampicin should be based on a schedule of 8 - 12 mg/kg body mass. Doses towards the lower end of this range are recommended for frail and elderly patients. A dose of 8 mg/kg body mass should not be exceeded in patients with impaired liver function. RIFINAH Tablets is unsuitable for children under 12 years of age.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Hepatic reactions; see under "Warnings".
Rifampicin: Reactions occurring with either daily or intermittent dosage regimens include:
- Cutaneous reactions, which are self-limiting, may occur and do not appear to be hypersensitivity reactions. Typically they consist of flushing and itching with or without a rash. More serious hypersensitivity cutaneous reactions may also occur, but are uncommon. Pemphigoid reaction, erythema multiforme including Stevens-Johnson syndrome, toxic epidermal necrolysis and vasculitis have been reported.
- Gastro-intestinal reactions consist of anorexia, nausea, vomiting, abdominal discomfort, diarrhoea and pseudomembranous colitis.
- Disseminated intravascular coagulation has also been reported.
Eosinophilia, leucopenia, oedema, muscle weakness and myopathy have been reported. Other side-effects include confusion, drowsiness, headache, ataxia, dizziness, haemolysis and generalised numbness.
Reactions usually occurring with intermittent dosage regimens and most probably of immunological origin include: "Flu Syndrome" consisting of episodes of fever, chills, headache, dizziness, bone pain and malaise; Shortness of breath and wheezing; Decrease in blood pressure and shock; Acute haemolytic anaemia; Acute renal failure usually due to acute tubular necrosis or to acute interstitial nephritis; Anaphylaxis.
Reports of adrenal insufficiency in patients with compromised adrenal function have been observed. Occasional disturbances of menstrual cycle have been reported. Rifampicin may produce reddish colouration of the urine, sputum, and tears and the patient should be forewarned of this. Soft contact lenses may be permanently stained. Blurred vision has been reported.
Isoniazid: Polyneuritis associated with isoniazid presenting as paraesthesia, muscle weakness, loss of tendon reflexes, etc. may occur. Various haematological disturbances including eosinophilia, agranulocytosis, thrombocytopenia and anaemia may occur. Gastrointestinal reactions may include nausea, vomiting and epigastric distress. High doses of isoniazid can cause convulsions. The frequency of seizures may be increased in patients with epilepsy.
Other neurotoxic effects, which are uncommon with conventional doses, are toxic encephalopathy, optic neuritis and atrophy, memory impairment, and toxic psychosis. Other side-effects of isoniazid are skin reactions, hyperglycaemia, acidosis, lupus-like reactions, a rheumatic syndrome and gynaecomastia.

DRUG/LABORATORY INTERACTIONS:
Rifampicin
: Has liver enzyme-inducing properties and may reduce the activity of a number of drugs including; warfarin, corticosteroids, cyclosporin, digitalis preparations, oral hypoglycaemic agents, dapsone, narcotics and analgesics.
The prothrombin time of patients receiving concurrent anticoagulant therapy may be decreased. Frequent monitoring of the prothrombin level in such patients with subsequent adjustment in anticoagulant dosage, is recommended. Rifampicin has been reported to diminish the effects of methadone, barbiturates, benzodiazepines, calcium channel blockers, beta-adrenergic blockers, clofibrate, progestins, antiarrythmics (e.g. quinidine)¸ doxycycline, fluoroquinolones, levothyroxine, nortriptyline, zidovudine, theophylline, tacrolimus, chloramphenicol, antifungals and anticonvulsants (e.g. phenytoin). It may be necessary to adjust the dosage of these medicines.
Patients using oral contraceptives should be advised to change to non-hormonal methods of birth control during rifampicin therapy as rifampicin reduces the efficacy of oral contraceptives. Diabetes may become more difficult to control. Antacids have been shown to interfere with the absorption of rifampicin. Halothane has been reported to increase the hepatotoxicity of both compounds. Ketoconazole has been reported to diminish serum concentrations of both compounds. The concentration of enalaprilat, the active metabolite of enalapril, may be decreased. Dosage should be adjusted if indicated by the patient's clinical condition.
Standard microbiological assays for serum folate and vitamin B12 may be inhibited. Transient elevation of serum bilirubin has also been observed and the test should therefore be performed before the morning dose of rifampicin.
Isoniazid: May decrease the excretion of phenytoin or enhance its effect.
Appropriate adjustment of the anticonvulsant dose should be made.
Daily ingestion of alcohol may be associated with higher incidence of isoniazid hepatitis. Isoniazid inhibits the metabolism of primidone and increases the toxicity of disulfiram.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See under "Side-effects and Special Precautions".
Symptoms more likely to be related to isoniazid include respiratory distress, coma, hyperglycaemia and metabolic acidosis. Gastric lavage should be performed as soon as possible. Treatment is symptomatic and supportive.

IDENTIFICATION:
RIFINAH-150: Cyclamen-coloured, round, sugar-coated tablets.
RIFINAH-300: Orange, capsule shaped, sugar-coated tablets.

PRESENTATION:
RIFINAH-150 - Packs of 20 and 60 tablets.
RIFINAH-300 - Packs of 20 and 40 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C in a dry place.
Keep out of reach of children.

REGISTRATION NUMBER:
RIFINAH-150: G/20.2.3/34
RIFINAH-300: G/20.2.3/35

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Aventis Pharma (Pty) Ltd., 2 Bond Street, Midrand, 1685.

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
17.10.1986.

Aventis Pharma (Pty) Ltd
2 Bond Street
Midrand
1685

        89010979

Updated on this site: April 2005
Source: Hospital Pharmacy

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