Rifampicin + Isoniazid


Concise Prescribing Info
Indications/Uses
Tuberculosis.
Dosage/Direction for Use
Adult : PO Each tab contains rifampicin and isoniazid (mg): <50 kg: 3 tab of 150/100 once daily; ≥50 kg: 2 tab of 300/150 once daily.
Dosage Details
Oral
Tuberculosis
Adult: Each tab contains rifampicin and isoniazid (mg): <50 kg: 3 tab of 150/100 once daily; ≥50 kg once daily: 2 tab of 300/150 once daily.
Hepatic Impairment
Max: 8 mg/kg daily.
Administration
Should be taken on an empty stomach. Take at least 30 min before or 2 hr after meals.
Contraindications
Hypersensitivity. Patient w/ jaundice. Concomitant use w/ saquinavir/ritonavir combination.
Special Precautions
History of DM, psychosis, peripheral neuropathy. Patient w/ HIV infection, porphyria, malnutrition, slow acetylator status, epilepsy and alcohol dependence. Hepatic and severe renal impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
GI symptoms (e.g. anorexia, nausea, vomiting, constipation, diarrhoea), alterations in liver function, peripheral neuritis, optic neuritis, headache, drowsiness, convulsions, vertigo, blood disorders (e.g. leucopenia, haemolytic anaemia, aplastic anaemia, eosinophilia), dry mouth, itching w/ or w/o rash, flushing, urticaria, rash, purpura, pancreatitis, oedema, interstitial pneumonitis, hyperreflexia, hyperglycaemia, adrenal insufficiency, gynaecomastia, menstrual disturbances, difficulty in micturition, muscular weakness, myopathy, SLE-like syndrome, pellagra, exfoliative dermatitis, pemphigus, toxic epidermal necrolysis, pemphigoid reactions, orange-red discolouration of urine, saliva and other body secretions; hearing loss and tinnitus, influenza-like symptoms, resp symptoms, collapse and shock, thrombocytopenic purpura, disseminated intravascular coagulation, acute renal failure. Rarely, psychoses, pemphigoid reaction, erythema multiforme, Lyells syndrome and vasculitis.
Potentially Fatal: Severe/fatal hepatitis (e.g. jaundice).
Patient Counseling Information
May impair ability to drive or operate machinery. May produce a reddish colouration of the urine, sweat, sputum, and tears. May permanently stain soft contact lenses. Patient should change from oral contraceptives to non-hormonal methods of birth control.
MonitoringParameters
Monitor hepatic enzymes and function, bilirubin, serum creatinine, CBC and platelet count.
Overdosage
Symptoms: Rifampicin: Nausea, vomiting, abdominal pain, pruritus, headache, increasing lethargy, unconsciousness, transient increases in liver enzymes and/or bilirubin; brownish-red or orange colouration of the skin, urine, sweat, saliva and faeces; facial or periorbital oedema, hypotension, sinus tachycardia, ventricular arrhythmias, seizures, cardiac arrest. Isoniazid: Nausea, vomiting, dizziness, slurred speech, blurred vision, visual hallucinations, resp distress, CNS depression, progressing rapidly from stupor to profound coma, along w/ severe, intractable seizures; severe metabolic acidosis, acetonuria, hyperglycaemia. Management: Perform gastric lavage as soon as possible, followed by admin of activated charcoal. Antiemetic drug may be required to control severe nausea and vomiting. Symptomatic and supportive treatment, including airway patency. May admin IV pyridoxine if acute isoniazid overdose is suspected, or anticonvulsant therapy in seizures not controlled by pyridoxine. Na bicarbonate should be given to control metabolic acidosis.
Drug Interactions
May reduce effectivity of hormonal contraceptives. Reduced absorption w/ antacids. May decrease plasma concentrations of antivirals (e.g. atazanavir, darunavir, fosamprenavir), atovaquone w/ rifampicin. Rifampicin may reduce serum levels of the following drugs: anticonvulsants (e.g., phenytoin), antiarrhythmics (e.g. disopyramide), oral anticoagulants, antifungals (e.g. ketoconazole), barbiturates, β-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 w/ halothane. Isoniazid 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 w/ isoniazid. Loss of glucose control in patients on oral hypoglycaemics w/ isoniazid.
Potentially Fatal: Concurrent treatment w/ saquinavir/ritonavir combination may result to severe hepatotoxicity.
Food Interaction
Absorption may be reduced and delayed w/ food. Increased adverse reaction w/ tyramine-containing foods (e.g. cheese, red wine) and histamine-containing foods (e.g. tuna, other tropical fish). Alcohol may increase the risk of hepatotoxicity.
Lab Interference
May inhibit standard microbiological assays for serum folate and vit B12. May impair biliary excretion of contrast media used for visualisation of the gallbladder.
Action
Description: Rifampicin and isoniazid 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 w/ bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance to rifampicin has only been shown w/ other rifamycins. It has activity against slow- and intermittently-growing M. tuberculosis. Isoniazid acts against actively growing tubercle bacilli.
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract. Food may reduce and delay absorption. Time to peak plasma concentration: 1-2 hr (isoniazid); 2-4 (rifampicin).
Distribution: Rifampicin: Widely distributed in body tissues and fluids. Crosses the placenta and enters breast milk. Plasma protein binding: Approx 80%. Isoniazid: Distributed into all body tissues and fluids, including CSF. Crosses the placenta and enters breast milk.
Metabolism: Rifampicin: Rapidly metabolised hepatically, mainly to active 25-O-deacetylrifampicin. Isoniazid: Hepatic, via acetylation of isoniazid to acetylisoniazid by N-acetyltransferase. Acetylisoniazid is then hydrolysed to isonicotinic acid and monoacetylhydrazine. Isonicotinic acid is conjugated w/ glycine to isonicotinyl glycine (isonicotinuric acid) and monoacetylhydrazine is further acetylated to diacetylhydrazine. Some unmetabolised isoniazid is conjugated to hydrazones.
Excretion: Rifampicin: Via urine (up to 30%; approx half of it as unchanged drug) and faeces (approx 60%). Half-life: 2-5 hr. Isoniazid: Via urine (>75% mainly as metabolites) and faeces (small amounts). Plasma half-life: Approx 1-6 hr.
Storage
Store below 25°C.
MIMS Class
References
Buckingham R (ed). Isoniazid. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2014.

Buckingham R (ed). Rifampicin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2014.

Joint Formulary Committee. Rifampicin with Isoniazid. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2014.

Rifamate Capsule (Sanofi-Aventis U.S. LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 01/07/2014.

Disclaimer: This information is independently developed by MIMS based on Rifampicin + Isoniazid from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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