AFDC-2^®

AFDC^®-2 is a combination of Rifampicin and lsoniazid. Both are active bactericidal anti-TB drugs which are particularly active against the rapidly growing extracellular organisms and also have bactericidal activity intracellularly. Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance to rifampicin has only been shown with other rifamycins. It has activity against slow and intermittently growing M. tuberculosis. Isoniazid acts against actively growing tubercle bacili.

Use in patients with body weight less than 30 kg
AFDC^®-2 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 Bs) may be useful.

Hepatic insufficiency
AFDC^®-2 should be used with caution and under strict medical supervision in impaired liver function. AFDC^®-2 is contraindicated in patients with a history of drug induced hepatitis and in patients with acute liver diseases.

Renal insufficiency
AFDC^®-2 should be used with caution in patients with moderate renal impairment (creatinine clearance 25-60 ml/min). AFDC®-2 is contraindicated in patients with severe renal impairment (creatinine clearance< 25 ml/min).

Interruption of treatment
If continuation phase treatment with AFDC^®-2 is interrupted for any reason including noncompliance, AFDC^®-2 is contraindicated for the resumption of treatment. Rifampicin and isoniazid 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-tuberculosis agents.

AFDC^®-2 is used for the continuation phase treatment of tuberculosis.

Route of administration: AFDC^®-2 should be taken in oral route. AFDC^®-2 should be given as a single dose (number of tablets depending on the patient's bodyweight), in a fasting state at least 1 hour before a meal.
AFDC^®-2 is a fixed combination product intended for use in the continuation phase of antituberculous treatment. This combination should be administered on a daily basis throughout the 4 month continuation phase of treatment.
This combination should only be used when the fixed ratio of rifampicin 150 mg and isoniazid 75 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.

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 and isoniazid pass into the breast milk, but no adverse 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.

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.

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 in children under 6 years of age because of risk of aspiration. 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. 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.

Rifampicin may cause reddish discoloration of body fluids and occasionally other body secretions e.g., urine, sputum, lacrimal fluid, faeces, saliva and sweat. It may permanently discolor soft contact lenses. Most common side effects which may occur during continuous daily or intermittent therapy:
Hepatic effects: Very common is an asymptomatic increase in liver enzymes; severe life-threatening hepatic reactions e.g., hepatic failure and acute fulminant hepatitis are uncommon. In isolated cases a fatal outcome was observed.
Renal effects: Elevations of BUN and serum uric acid, hemolysis, hematuria, interstitial nephritis, renal insufficiency.
Gastrointestinal effects: Nausea, abdominal pains, vomiting or diarrhea, pseudomembranous colitis.
Central and peripheral nervous system effects: Tiredness, drowsiness, headache, dizziness, ataxia, mental confusion, muscular weakness and visual disturbances.
Hematological changes: Leucopenia, eosinophilia, thrombocytopenia and thrombocytopenic purpura.
Effects on skin and appendages: Flushing, itching with or without skin rash, urticaria, reddening of the eyes, exudative conjunctivitis or generalized hypersensitivity reactions involving the skin e.g., exfoliative dermatitis, Lyell's syndrome and pemphigoid reactions.
Endocrine effects: Disturbances in the menstrual cycle, induction of crisis in Addison patients. Unwanted effects chiefly occurring during intermittent therapy or upon resumption of treatment after temporary interruption.

It is contraindicated in patients with a history of hypersensitivity to rifampicin, isoniazid 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 and porphyria. 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. May reduce effectivity of hormonal contraceptives. Reduced absorption with antacids. May decrease plasma concentrations of antivirals (e.g. atazanavir, darunavir, fosamprenavir), atovaquone with rifampicin. Rifampicin may reduce serum levels of anticonvulsants (e.g. phenytoin), antiarrhythmics (e.g. disopyramide), oral anticoagulants, antifungals (e.g. ketoconazole), barbiturates, beta-blockers, Ca channel blockers (e.g. diltiazem), chloramphenicol, clarithromycin, corticosteroids, ciclosporin, cardiac glycosides, clofibrate, dapsone, diazepam, doxycycline, fluoroquinolones (e.g. ciprofloxacin), haloperidol, oral hypoglycemic agents (sulfonylureas), levothyroxine, methadone, narcotic analgesics, progestins, quinine, tacrolimus, theophylline, TCAs (e.g. amitriptyline, nortriptyline) and zidovudine. Increased risk of hepatotoxicity with halothane. lsoniazid may inhibit the metabolism of anticonvulsants (e.g. carbamazepine, phenytoin), benzodiazepines (e.g. diazepam), haloperidol, ketoconazole, theophylline, and warfarin. May enhance the CNS effects of meperidine, cycloserine, and disulfiram with isoniazid. Loss of glucose control in patients on oral hypoglycemic with isoniazid.
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.

lsoniazid: 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.

No Data

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

AFDC^®-2 tablet: Each film coated tablet contains Rifampicin BP 150 mg and lsoniazid BP 75 mg.

AFDC^®-2 tablet: Carton of 672 tablets in blister pack.