Rifater

Rifater

rifampicin + isoniazid + pyrazinamide

Manufacturer:

Sanofi-Aventis

Distributor:

DKSH
Full Prescribing Info
Contents
Rifampicin, isoniazid, pyrazinamide.
Description
Each tablet contains rifampicin 120 mg, isoniazid 80 mg and pyrazinamide 250 mg.
Action
Antibacterial. Antituberculosis drug.
Pharmacology: Rifampicin, isoniazid and pyrazinamide are all active bactericidal antituberculosis drugs. Rifampicin and isoniazid are particularly active against the rapidly growing extracellular organisms.
Pyrazinamide is active against intracellular organisms, particularly in the acid pH environment of macrophages.
Rifampicin and isoniazid also have bactericidal activity intracellularly. Rifampicin has activity against slow and intermittently-growing M. tuberculosis. Thus, the 3 agents, rifampicin, isoniazid and pyrazinamide have activity against the 3 different bacterial populations.
Pharmacokinetics: Studies in normal volunteers have shown that the 3 ingredients in Rifater have comparable bioavailability whether they are given together as individual dose forms or as Rifater.
Indications/Uses
Tuberculosis: Rifater is indicated in the initial intensive phase of the short-course treatment of tuberculosis. During this phase, which usually lasts 2 months, Rifater is usually administered on a daily, continuous basis. When indicated, other antituberculosis drug, eg streptomycin, may be added.
Following the initial intensive phase, treatment should be continued with rifampicin and isoniazid (Rifinah) for a further 4 months minimum.
Dosage/Direction for Use
The daily dosage range for the 3 essential bactericidal drugs recommended by international authorities in the initial 2-month intensive phase of short-course therapy is: Rifampicin: 8-12 mg/kg, isoniazid: 4-10 mg/kg, pyrazinamide: 15-30 mg/kg.
Each sugar-coated Rifater tablet contains: Rifampicin 120 mg, isoniazid 80 mg, pyrazinamide 250 mg.
Patients should be given the following single daily dose 1-2 hrs before a meal: 1 tab/10 kg body weight, not exceeding 5 tabs/dose.
Patients weighing ≥50 kg: 5 tabs; <50 kg: 4 tabs.
Alternatively, the following dosage regimen may be used:
Patients weighing ≥50 kg: 5 tabs; 40-49 kg: 4 tabs; 30-39 kg: 3 tabs.
This intensive phase should be continued usually for 2 months. When indicated, other antituberculosis drugs, eg streptomycin may be added.
Following the initial intensive phase, treatment should be continued with rifampicin and isoniazid (Rifinah) for a further 4 months minimum.
Overdosage
In cases of overdosage with Rifater, gastric lavage should be performed as soon as possible. Intensive supportive measures should be instituted and individual symptoms treated as they arise. Parenteral pyridoxine (vitamin B6) should be given. Symptoms are more likely to be related to isoniazid, including coma, respiratory distress, hyperglycaemia and metabolic ketoacidosis.
Contraindications
Patients with a history of sensitivity to rifamycins, isoniazid or pyrazinamide. Rifater is contraindicated in the presence of jaundice.
Special Precautions
Rifater is a combination of 3 drugs, each of which has been associated with liver dysfunction.
Patients with impaired liver function should only be given Rifater 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 2-4 weeks during therapy. If signs of hepatocellular damage occur, Rifater should be withdrawn. Care should be exercised in the treatment of elderly or malnourished patients who may also require vitamin B6 supplementation with the isoniazid therapy.
In some cases, hyperbilirubinemia resulting from competition between rifampicin and bilirubin for excretory pathways of the liver at the cell level can occur in the early days of treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather, the decision should be made after repeating the tests, noting trends in the levels and considering them in conjunction with the patients clinical conditions.
Rifater should be used with caution in patients with a history of gout. If hyperuricaemia accompanied by an acute gouty arthritis occurs, the patient should be transferred to a regimen not containing pyrazinamide (eg, Rifinah 150 or 300).
Because of the possibility of immunological reaction (see Adverse Reactions) occurring with intermittent rifampicin therapy (<2-3 times/week), patients should be closely monitored. Patients should be cautioned against interruption of dosage regimens since these reactions may occur.
Use in pregnancy & lactation: Rifampicin has been shown to be teratogenic in rodents when given in large doses. There are no well-controlled studies with Rifater in pregnant women. Therefore, Rifater should be used in pregnant women or in women of childbearing potential only if the potential benefit justifies the potential risk to the fetus.
When administered during the last few weeks of pregnancy, rifampicin can cause postnatal hemorrhages in the mother and infant, for which, treatment with vitamin K may be indicated.
Rifampicin and isoniazid are excreted in breast milk and infants should not be breastfed by a patient receiving Rifater unless the physician's judgment the potential benefit to the patient outweighs the potential risk to the infant.
Use In Pregnancy & Lactation
Rifampicin has been shown to be teratogenic in rodents when given in large doses. There are no well-controlled studies with Rifater in pregnant women. Therefore, Rifater should be used in pregnant women or in women of childbearing potential only if the potential benefit justifies the potential risk to the fetus.
When administered during the last few weeks of pregnancy, rifampicin can cause postnatal hemorrhages in the mother and infant, for which, treatment with vitamin K may be indicated.
Rifampicin and isoniazid are excreted in breast milk and infants should not be breastfed by a patient receiving Rifater unless the physician's judgment the potential benefit to the patient outweighs the potential risk to the infant.
Adverse Reactions
Rifampicin: Reactions to rifampicin occurring with either daily or intermittent dosage regimens include:
Cutaneous reactions which are mild and 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 occur but are uncommon.
Gastrointestinal reactions consist of anorexia, nausea, vomiting, abdominal discomfort and diarrhea. Pseudomembranous colitis has been reported with rifampicin therapy.
Hepatitis can be caused by rifampicin and liver function tests should be monitored. (See Precautions.)
Thrombocytopenia with or without purpura may occur, usually associated with intermittent therapy but is reversible if drug is discontinued as soon as purpura occurs. Cerebral hemorrhage and fatalities have been reported when rifampicin administration has been continued or resumed after the appearance of purpura.
Eosinophilia, leukopenia, edema, muscle weakness and myopathy have been reported in a small percentage of patients treated with rifampicin.
Reactions usually occurring with intermittent dosage regimens and most probably of immunological origin include:
Flu syndrome consisting of episodes of fever, chills, headache, dizziness and bone pain appearing most commonly during the 3rd to the 6th month of therapy. The frequency of the syndrome varies but may occur in up to 50% of patients given once-weekly regimens with a dose of rifampicin of ≥25 mg/kg.
Shortness of breath and wheezing.
Decrease in blood pressure and shock.
Acute hemolytic anemia.
Acute renal failure usually due to acute tubular necrosis but cortical necrosis has been reported.
Occasional disturbances of the menstrual cycle have been reported in women receiving long-term antituberculosis therapy with regimens containing rifampicin.
Rifampicin may produce a reddish coloration of the urine, sputum and tears and the patient should be forewarned of this. Soft contact lenses may be permanently stained.
Isoniazid: Severe and sometimes fatal hepatitis may occur with isoniazid therapy. Polyneuritis associated with isoniazid, presenting as paraesthesia, muscle weakness, loss of tendon reflexes, etc, is unlikely to occur with the recommended daily dose of Rifater. Various hematological disturbances have been identified during treatment with isoniazid, including eosinophilia, agranulocytosis and anemia. High doses of isoniazid can cause convulsions. The possibility that the frequency of seizures may be increased in patients with epilepsy should be borne in mind.
Pyrazinamide: Adverse reactions, other than hepatic reaction, which have been attributed to pyrazinamide are active gout (pyrazinamide has been reported to reduce urate excretion), sideroblastic anaemia, arthralgia, anorexia, nausea and vomiting, dysuria, malaise, fever, urticaria and aggravation of peptic ulcer. The hepatic reaction is the most common adverse reaction and varies from a symptomless abnormality of hepatic cell function detected only through laboratory liver function tests, through a mild syndrome of fever, malaise and liver tenderness, to more serious reactions as clinical jaundice and rare cases of acute yellow atrophy and death.
Drug Interactions
Rifampicin has liver enzyme-inducing properties and may reduce the activity of a number of drugs including anticoagulants, corticosteroids, cyclosporin, digitalis preparations, quinidine, oral contraceptives, oral hypoglycemic agents, dapsone, narcotics and analgesics. It may be necessary to adjust the dosage of these drugs if they are given concurrently with Rifater.
Patients using oral contraceptives should be advised to change to nonhormonal methods of birth control during Rifater therapy.
Also, diabetes may become more difficult to control. When rifampicin is taken with para-aminosalicylic acid (PAS), rifampicin levels in the serum may decrease. Therefore, the drugs should be taken at least 4 hrs apart. Therapeutic levels of rifampicin have been shown to inhibit standard microbiological assays for serum folate and vitamin B12. Thus, alternate assay methods should be considered. Transient elevation of BSP and serum bilirubin have been reported. Therefore, these tests should be performed before the morning dose of rifampicin.
Isoniazid may decrease the excretion of phenytoin or may enhance its effects. Appropriate adjustment of anticonvulsant dose should be made.
MIMS Class
ATC Classification
J04AM05 - rifampicin, pyrazinamide and isoniazid ; Belongs to the class of combination drugs used in the systemic treatment of tuberculosis.
Presentation/Packing
Tab (sugar-coated) 4x 15's.
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