Adult: For continuation phase: Rifampicin 150 mg and isoniazid 75 mg tab
In patients weighing 30-<40 kg: 2 tabs once daily; 40-<55 kg: 3 tabs once daily; 55-<71 kg: 4 tabs once daily; ≥71 kg: 5 tabs once daily.
Rifampicin 150 mg and isoniazid 100 mg tab
In patients weighing <50 kg: 3 tabs once daily.
Rifampicin 300 mg and isoniazid 150 mg tab
In patients weighing ≥50 kg: 2 tabs once daily.
Rifampicin 450 mg and isoniazid 400 mg tab
In patients weighing ≤50 kg: 1 tab once daily. Consider local guidelines on the appropriate use of anti-tuberculosis drugs. Dosage recommendations and available fixed-dose combinations may vary between countries (refer to specific product guidelines).
What are the brands available for Rifampicin + Isoniazid in India?
Isoniazid + Rifampicin Should be taken on an empty stomach. Take at least 30 min before or 2 hr after meals.
Contraindications
Hypersensitivity to rifampicin or isoniazid. Presence of jaundice; acute hepatic disease; history of severe adverse reactions to isoniazid (e.g. drug-induced hepatitis, chills, fever, arthritis). Concomitant use with saquinavir/ritonavir combination.
Special Precautions
Patient with epilepsy, history of psychosis, diabetes mellitus, alcohol dependence or history of alcoholism, history of peripheral neuropathy, HIV infection, porphyria. Slow acetylators of isoniazid. Malnourished patients. Hepatic and severe renal impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Paradoxical reaction, anaphylactic reaction; peripheral neuropathy; haematologic effects (e.g. thrombocytopenia, anaemia, leucopenia, eosinophilia); discolouration (yellow, orange, red or brown) of faeces, teeth (may be permanent) and body fluids (e.g. urine, sweat, saliva, sputum, tears); exacerbation of porphyria; cerebellar syndrome, including cerebellar ataxia, dysdiadochokinesis, ataxia, balance disorders, dysmetria, and nystagmus (particularly in patients with CKD); flu-like syndrome such as chills, pyrexia and malaise (particularly with intermittent use). Blood and lymphatic system disorders: Lymphadenopathy. Ear and labyrinth disorders: Vertigo. Eye disorders: Optic neuritis. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal discomfort, epigastric distress, constipation, dry mouth, pancreatitis. General disorders and administration site conditions: Oedema. Infections and infestations: Pseudomembranous colitis. Investigations: Increased blood bilirubin, AST, ALT, and blood creatinine; decreased blood pressure. Metabolism and nutrition disorders: Decreased appetite, hyperglycaemia, pellagra. Musculoskeletal and connective tissue disorders: Muscle weakness, bone pain, myopathy. Nervous system disorders: Headache, dizziness, convulsions. Psychiatric disorders: Psychotic disorder. Renal and urinary disorders: Acute kidney injury (usually due to tubulointerstitial nephritis or renal tubular necrosis). Reproductive system and breast disorders: Menstrual disorder, gynaecomastia. Respiratory, thoracic and mediastinal disorders: Wheezing, dyspnoea, interstitial lung disease or pneumonitis. Skin and subcutaneous tissue disorders: Pruritic rash, urticaria, pruritus, allergic dermatitis, pemphigoid, rash, acne, alopecia, SLE-like syndrome. Vascular disorders: Flushing, shock, vasculitis, bleeding. Potentially Fatal: Hepatitis; severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms syndrome, acute generalised exanthematous pustulosis); thrombotic microangiopathy manifested as thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome.
May cause discolouration (yellow, orange, red or brown) of teeth, urine, faeces, saliva, sputum, sweat, tears, and other body fluids. It may also cause permanent staining of soft contact lenses; remove soft contact lenses during therapy.
Monitoring Parameters
Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor coagulation tests during treatment (particularly in patients at risk of vitamin K deficiency); baseline and periodic LFTs (ALT, AST), serum bilirubin, uric acid, creatinine, and CBC. Perform periodic ophthalmic examinations. Assess for signs or symptoms of skin reactions and hepatotoxicity.
Overdosage
Symptoms: Rifampicin: Nausea, vomiting, abdominal pain, pruritus, headache, lethargy, impaired consciousness, periorbital or facial oedema; brownish-red or orange discolouration of the skin, urine, sweat, saliva, tears, and faeces; hypotension, sinus tachycardia, ventricular arrhythmias, seizures, cardiac arrest; liver enlargement (possibly with tenderness), jaundice, rapid increases in total and direct serum bilirubin and increased hepatic enzymes. Isoniazid: Nausea, vomiting, slurred speech, dizziness, blurred vision, visual hallucinations; respiratory distress and CNS depression, progressing rapidly from stupor to coma with severe, intractable convulsions; severe metabolic acidosis, hyperglycaemia and acetonuria. Management: Symptomatic and supportive treatment. Secure the airway and establish adequate respiratory exchange. Perform gastric lavage as soon as possible, then administer activated charcoal slurry to help absorb any remaining drug in the gastrointestinal tract. Administer antiemetics to control severe nausea and vomiting. For suspected acute isoniazid overdose, consider administration of IV pyridoxine, even in asymptomatic patients. If seizures are not controlled with pyridoxine, give anticonvulsant agents. Correct metabolic acidosis with Na bicarbonate. Haemodialysis or peritoneal dialysis may also be necessary.
Drug Interactions
Reduced absorption with antacids.
Rifampicin: May significantly reduce the exposure of lurasidone. May increase the metabolism and reduce the activity of anticonvulsants (e.g. phenytoin), antiarrhythmics (e.g. disopyramide, quinidine), oral anticoagulants (e.g. warfarin), antipsychotic agents (e.g. haloperidol), antifungal agents (e.g. ketoconazole, itraconazole), antiretroviral agents (e.g. indinavir, efavirenz, zidovudine), barbiturates, caspofungin, Ca channel blockers (e.g. diltiazem, nifedipine), β-blockers (e.g. bisoprolol, propranolol), antibiotics (e.g. fluoroquinolones, chloramphenicol, clarithromycin, telithromycin, doxycycline), corticosteroids, cardiac glycosides (e.g. digoxin), clofibrate, hormonal contraceptives (e.g. estrogens, progestins), hormone antagonists (e.g. tamoxifen, toremifene), dapsone, benzodiazepines (e.g. diazepam) or related agents (e.g. zopiclone), enalapril, losartan, clopidogrel, oral hypoglycaemic agents (e.g. sulfonylureas, thiazolidinediones), immunosuppressive agents (e.g. tacrolimus, ciclosporin), irinotecan, levothyroxine, narcotic analgesics, mifepristone, praziquantel, quinine, riluzole, selective 5-HT3 receptor antagonists (e.g. ondansetron), statins metabolised by CYP3A4 (e.g. simvastatin), theophylline, TCAs (e.g. amitriptyline), and hepatitis C antiviral agents (e.g. sofosbuvir). May increase the risk of hepatotoxicity with halothane, isoniazid and paracetamol. Concomitant use with atovaquone may result in increased rifampicin concentration and reduced atovaquone concentration.
Isoniazid: Increased risk of distal sensory neuropathy with stavudine. Increased renal clearance with zalcitabine. May increase plasma concentration and elimination half-life with para-aminosalicylic acid. May reduce serum concentration with corticosteroids. Increased risk of CNS toxicity with cycloserine. May increase the risk of hepatotoxicity with general anaesthetics. May reduce the plasma concentration of ketoconazole. May increase the plasma concentration of theophylline. May inhibit the metabolism of anticonvulsants (e.g. carbamazepine, primidone, phenytoin), benzodiazepines (e.g. diazepam), theophylline and warfarin. Potentially Fatal: Increased risk of hepatotoxicity with saquinavir/ritonavir combination.
Rifampicin: Concomitant use with other antibiotics causing vitamin K-dependent coagulopathy (e.g. cefazolin) may result in severe coagulation disorders, particularly with high doses.
Food Interaction
Reduced absorption with food.
Isoniazid: Increased risk of hepatotoxicity with alcohol. Concomitant administration with foods containing tyramine (e.g. cheese, red wine) or histamine (e.g. tuna) may result in headache, palpitations, flushing, or sweating; avoid concomitant intake.
Lab Interference
Rifampicin: May inhibit the standard microbiologic assay's ability to measure serum folate and vitamin B12. May reduce biliary excretion of contrast media used for gallbladder visualisation.
Action
Description: Mechanism of Action: Rifampicin, a rifamycin antimycobacterial, binds to the β subunit of DNA-dependent RNA polymerase, inhibiting bacterial RNA synthesis and thus blocking RNA transcription.
Isoniazid prevents the synthesis of mycolic acids, the essential components of the bacterial cell wall. It is bactericidal at therapeutic levels against actively growing extracellular and intracellular Mycobacterium tuberculosis. Synonym(s): Rifampicin: Rifampin. Pharmacokinetics: Absorption: Readily absorbed from the gastrointestinal tract. Reduced absorption with food.
Rifampicin: Time to peak plasma concentration: Approx 2 hours.
Isoniazid: Time to peak plasma concentration: 1-2 hours. Distribution: Crosses the placenta and enters breast milk.
Rifampicin: Widely distributed in the body tissues and fluids; increased diffusion in the CSF when meninges are inflamed. Plasma protein binding: Approx 80%.
Isoniazid: Distributed into all body tissues and fluids (including the CSF). Plasma protein binding: 10-15%. Metabolism: Rifampicin: Rapidly metabolised in the liver into 25-O-deacetylrifampicin (active metabolite). Undergoes enterohepatic recirculation.
Isoniazid: Metabolised in the liver by N-acetyltransferase to acetylisoniazid, which undergoes further hydrolysis to isonicotinic acid and monoacetylhydrazine. Isonicotinic acid is then conjugated with glycine to form isonicotinyl glycine, while monoacetylhydrazine is acetylated to form diacetylhydrazine. Excretion: Rifampicin: Via faeces (60-65% as unchanged drug); urine (≤30% as unchanged drug). Elimination half-life: Approx 2-3 hours.
Isoniazid: Via urine (75-95% as unchanged drug and metabolites); faeces and saliva (small amounts). Elimination half-life: 30-100 minutes (fast acetylators); 2-5 hours (slow acetylators).
Chemical Structure
Rifampicin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135398735, Rifampin. https://pubchem.ncbi.nlm.nih.gov/compound/Rifampin. Accessed Nov. 26, 2024.
Isoniazid Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3767, Isoniazid. https://pubchem.ncbi.nlm.nih.gov/compound/Isoniazid. Accessed Nov. 26, 2024.
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