AFDC-4^®

AFDC^®-4 is a combination of Rifampicin, Isoniazid, Ethambutol Hydrochloride and Pyrazinamide.

Rifampicin: It is a semi-synthetic derivative of rifamycin, suppresses bacterial RNA synthesis by binding to the B-subunit of DNA-dependent RNA polymerase, thus inhibiting the attachment of the enzyme to DNA, blocking RNA transcription and elongation. It does not inhibit the counterpart mammalian enzyme. Rifampicin has a bactericidal action and a potent sterilizing effect against both intracellular and extracellular tubercle bacill. Cross-resistance has been shown only with other rifamycin derivatives.

Isoniazid: It kills actively growing tuberde bacilli by inhibiting the biosynthesis of mycolic acids, which are the major components of the bacterial cell wall of Mycobactenum tuberculosis.

Pyrazinamide: Pyrazinamide, an antituberculous drug, is the pyrazine analog of nicotinamide. The precise mechanism of action of pyrazinamide is not known. Its metabolite, pyrazinoic acid, which is less active in vitro may possibly be involved in the in vivo activity of pyrazinamide.

Ethambutol hydrochloride: Ethambutol diffuses slowly into actively growing Mycobacteria cells eg, tubercle bacill. It inhibits the synthesis of one or more metabolites, thus causing impaired cell metabolism, arrest cell multiplication and Induce cell death. No cross-resistance with other agents has been demonstrated. Spectrum of Activity: Rifampicin, Isoniazid, Pyrazinamide and Ethambutol, at therapeutic levels, have demonstrated bactericidal activity against both intracellular and extracellular Mycobacterium tuberculosis organism.

No Data

AFDC^®-4 is indicated for the treatment of both pulmonary and extrapulmonary tuberculosis in the intensive initial phase of treatment.

Route of administration: AFDC-4 should be taken in oral route: AFDC^®-4 should be given as a single dose (number of tablets depending on the patient's body weight), in a fasting state at least 1 hour before a meal AFDC^®-4 is a fixed combination product intended for use in the initial intensive phase of anti-tuberculous treatment. AFDC^®-4 should be administered on a daily basis throughout the 2 month initial phase of treatment. When indicated, other anti-tuberculous medicinal products such as streptomycin may be added in the initial phase of treatment. AFDC^®-4 should only be used when the fixed ratio of rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg and ethambutol hydrochloride 275 mg will permit treatment of an individual patient in line with official recommendations and practice.

WHO-recommended number of tablets with fixed-dose combinations of anti-TB drugs
Continuation phase-daily

* In patients with previously treated sputum smear-posijive pulmonary tuberculosis: relapse, treatment after interruption, treatment failure, according to the category II of WHO recommendations.

Use in patients with body weight less than 30 kg:

AFDC^®-4 is not a suitable dosage form for use in the treatment of patients with a body weight of less than 30 kg.

Older people
No special dosage regimen is necessary, but concurrent hepatic and/or renal insufficiency should be taken into account. Supplementation of pyridoxine (vitamin B) may be useful.

Hepatic insufficiency
AFDC^®-4 should be used with caution and under strict medical supervision in impaired liver function. AFDC^®-4 is contraindicated in patients with a history of drug induced hepatitis and in patients with acute liver diseases.

Renal insufficiency
AFDC^®-4 should be used with caution in patients with moderate renal impairment (creatinine clearance 25-60 ml/min). AFDC^®-4 is also contraindicated in patients with severe renal impairment (creatinine clearance <25 ml/min).

Interruption of treatment
If initial intensive phase treatment with this combination is interrupted for any reason including non-compliance, AFDC^®-4 is contraindicated for the resumption of treatment. Rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride must be administered separately for the resumption of treatment, because rifampicin needs to be reintroduced at a lower dose, Reference should be made to official guidance on the appropriate resumption of treatment with anti-tuberculous agents.

Pregnancy: Treatment should be considered on a case by case basis after benefit of medicinal product combination has been assessed. Consequently, this combination could be given during pregnancy if the potential benefit for the mother is judged to outweigh the potential risk to the fetus.

Lactation: Rifampicin, isoniazid, pyrazinamide and ethambutol pass into the breast milk, but no undesirable effects on breast-fed infants have been observed. Breast-feeding is, however, not recommended in view of the theoretical possibility of neurotoxic effects due to isoniazid and ethambutol.

Use in children and adolescents
This combination is not a suitable dosage form for use in the treatment of children with a body weight of less than 30 kg. It is not recommended in children under 6 years of age because of risk of aspiration and possible difficulties in evaluation of changes of visual acuity.

In cases of known acetylation phenotypes, patients with extremely fast or extremely slow acetylating capability should receive the two components separately in order to facilitate dose adjustment of isoniazid. This combination should be withdrawn immediately if severe acute hypersensitivity reactions occur, such as thrombocytopenia, purpura, hemolytic anemia, dyspnea and asthma-like attacks, shock or renal failure as these are side effects that rifampicin may provoke in exceptional cases. Patients developing such reactions must never again be treated with rifampicin. It should be withdrawn if other signs of hypersensitivity appear, such as fever or skin reactions. For safety reasons, treatment should not be continued or resumed with rifampicin. This combination is not recommended for children under 6 years of age because of risk of aspiration and because of the ethambutol hydrochloride component. Visual disturbances that may occur as a result of using ethambutol and that require immediate discontinuation of treatment may be difficult to diagnose in young children. It is not a suitable dosage form for use in the treatment of patients with a body weight of less than 30 kg. It should be used with caution and under strict medical supervision in impaired liver function and moderate renal impairment (creatinine clearance 25-60 ml/min) patients.

Rifampicin, isoniazid, pyrazinamide and ethambutol are metabolized in the liver. Elevated transaminase levels, above the upper limit of normal (ULN), commonly occur. Liver dysfunction that may occur in the first few weeks of treatment usually returns to the normal range spontaneously, without interruption of treatment, and usually by the third month of treatment. Pyrazinamide and ethambutol should be used with caution in patients with a history of gout. Additional non-hormonal means of contraception must be employed to prevent the possibility of pregnancy during treatment with rifampicin. Patients suffering from convulsive disorders must be kept under special observation during treatment with this combination because of the neurotoxic effects of isoniazid. Caution should be exercised in subjects with peripheral neuritis.

No Data

It is contraindicated in patients with a history of hypersensitivity to rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride or any of its components. It is also contraindicated in patients with severe renal impairment (creatinine clearance < 25 ml/min) & a history of drug induced hepatitis and in patients with acute liver diseases, porphyria and acute gouty arthritis. Concomitant use with voriconazole and protease inhibitors, except ritonavir when given at full dose or 600 mg twice daily is also contraindicated.

Drug interaction with medication: Antacids reduce the bioavailability of rifampicin and isoniazid. To avoid this interaction, it should be taken at least 1 hour before antacids, Corticosteroids can reduce the plasma levels of isoniazid, by increasing its metabolic and/or renal clearance.

Rifampicin: Induces microsomal enzymes (accelerates clearance of methadone, oral anticoagulants, glucocorticoids, oestrogen, oral hypoglycaemic agents, digitoxin, antiarrhythmics, theophylline, anticonvulsants, azole antifungal, cyclosporin).

Isoniazid: Inhibits metabolism of antiepileptics, benzodiazepines, warfarin, and theophylline, Increases metabolism of enflurane, Alcohol, ASA, AL-containing antacids, corticosteroids, ketoconazole, propranolol.

Pyrazinamide: Decreases efficacy of gout therapy agents.

Ethambutol HCI: Neurotoxic agents.

Drug interaction with food and others: The rate and extent of absorption is decreased when this combination is taken with food. Should avoid food with a high content of tyramine (like cheese, red wine) or histamine (like tuna fish). This food taken together with this combination may lead to headache, palpitations or flushing. Take this medicine at least one hour before a meal.

Rifampicin: Nausea, vomiting, abdominal pain, pruritus, headache and increasing lethargy will probably occur within a short time after acute ingestion; unconsciousness may occur when there is severe hepatic disease, Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange coloration of the skin, urine, sweat, saliva, tears and faeces will occur, and its intensity is proportional to the amount ingested. Facial or periorbital edema has also been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.

Isoniazid: Typical symptoms are seizures, metabolic acidosis, ketonuria, and hyperglycemia. In addition, periorbital myoclonus, dizziness, tinnitus, tremor, hyperreflexia, paresthesia, hallucinations, impaired consciousness, respiratory depression, apnea, tachycardia, arrhythmias, hypotension, nausea, vomiting, fever, rhabdomyolysis, DIC, hyperglycemia, hyperkalemia, liver involvement. Doses of isoniazid exceeding 10 mg/kg may adversely affect the nervous system, e.g. in the form of peripheral neuropathy, and thus impair the patient's ability to drive or operate machinery.

Pyrazinamide: Abnormal liver function tests, hyperuricemia.

Ethambutol HCI: Loss of appetite, gastrointestinal disturbances, fever, headache, dizziness, confusion, hallucinations.

No Data

Store in a cool (below 30°C) and dry place protected from light. Keep away from the reach of children.

AFDC^®-4 tablet Each film coated tablet contains Rifampicin BP 150 mg, Isoniazid BP 75 mg. Pyrazinamide BP 400 mg and Ethambutol Hydrochloride USP 275 mg.

AFDC^®-4 tablet: Carton of 672 tablets in blister pack.