Rifampicin + isoniazid + pyrazinamide


Concise Prescribing Info
Indications/Uses
Pulmonary tuberculosis.
Dosage/Direction for Use
Adult: PO For the initial intensive phase of the short-course treatment: Each tab contains rifampicin (mg)/isoniazid (mg)/pyrazinamide (mg): 120/50/300: <40 kg: 3 tablets/day; 40-49 kg: 4 tablets/day; 50-64 kg: 5 tablets/day; ≥65 kg: 6 tablets/day. Initial phase usually lasts for 2 months with doses given on a daily continuous basis.
Administration
Should be taken on an empty stomach. Take on an empty stomach 1 hr before or 2 hr after meals. Avoid antacids w/in 1 hr of intake.
Contraindications
Hypersensitivity. History of severe adverse reaction to isoniazid, acute liver disease, jaundice, acute gout. Severe hepatic impairment. Concomitant use with praziquantel, darunavir, atazanavir, fosamprenavir, saquinavir, saquinavir/ritonavir, or tipranavir.
Special Precautions
Patient with diabetes mellitus, chronic gout, risk factors of vitamin K deficiency (e.g. chronic liver disease, poor nutritional status, prolonged use of antibacterials or anticoagulants); epilepsy, history of alcoholism, psychosis, peripheral neuropathy; HIV infection, haemoptysis, porphyria. Renal and mild to moderate hepatic impairment. Pregnancy and lactation. Slow acetylator status. Patient Counselling This drug may cause vertigo, visual disorder and psychotic reactions; if affected, do not drive or operate machinery. May produce a discolouration (e.g. red, orange, brown, yellow) of the urine, faeces, saliva, teeth, sweat, and tears. Soft contact lenses may be permanently stained; 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 LFTs at baseline and every 2-4 weeks particularly in patients at risk of hepatitis; CBC and platelet count, serum bilirubin, serum uric acid, and serum creatinine at baseline and periodically thereafter; coagulation test during therapy in patients at risk of vitamin K deficiency. Monitor sputum cultures monthly; chest x-ray after 2-3 months of therapy and at completion. Closely monitor for prodromal signs of hepatitis and skin reactions. Perform ophthalmologic examination periodically (even if visual symptoms do not occur).
Adverse Reactions
Significant: Vitamin K-dependent coagulation disorder and bleeding, flu-like syndrome, haematologic effects (e.g. thrombocytopenia, leucopenia, anaemia); hypersensitivity reactions (e.g. fever, rash, urticaria, angioedema), porphyria exacerbation, peripheral neuropathies, hyperuricaemia with acute gouty arthritis; superinfection, including C. difficile-associated diarrhoea and pseudomembranous colitis. Cardiac disorders: Angina pectoris, chest tightness, palpitations. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, gastrointestinal pain. General disorders and administration site conditions: Fever, chills, oedema. Investigations: Increased blood bilirubin, increased AST and ALT. Metabolism and nutrition disorders: Diabetic coma, anorexia. Musculoskeletal and connective tissue disorders: Arthralgia, ostealgia. Nervous system disorders: Headache, dizziness. Psychiatric disorders: Anxiety, insomnia. Respiratory, thoracic and mediastinal disorders: Haemoptysis, pneumothorax, cough. Skin and subcutaneous tissue disorders: Erythema, erythroderma, exfoliative dermatitis, localised rash, pruritus, diaphoresis.
Potentially Fatal: Hepatotoxicity (e.g. severe hepatitis, isolated jaundice, hyperbilirubinaemia, fulminant liver failure), severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms syndrome [DRESS]).
Drug Interactions
Rifampicin: Decreased plasma concentrations of praziquantel to undetectable levels. May induce the metabolism and decrease the serum concentrations and effects of antiarrhythmics (e.g. disopyramide, quinidine), antiepileptics (e.g. phenytoin), hormone antagonist (e.g. antioestrogens, tamoxifen), antipsychotics (e.g. haloperidol, aripiprazole), anticoagulants (e.g. warfarin), antifungals (e.g. fluconazole, itraconazole), barbiturates, anxiolytics and hypnotics (e.g. diazepam), Ca channel blocker (e.g. diltiazem, nifedipine), antibacterials (e.g. clarithromycin, chloramphenicol), corticosteroids, cardiac glycosides (e.g. digoxin), hormonal contraceptives (e.g. oestrogen, progesterone), antidiabetics (e.g. tolbutamide, sulfonylureas), immunosuppressive agents (e.g. ciclosporin), thyroid hormone (e.g. levothyroxine), analgesics (methadone), selective 5-HT3 receptor antagonist (e.g. ondansetron), TCAs (e.g. amitriptyline), cytotoxics (e.g. imatinib), diuretics (e.g. eplerenone), hepatitis-C antivirals (e.g. sofosbuvir), ACE inhibitors (e.g. enalapril), NSAIDS (e.g. etoricoxib), antiemetics (e.g. aprepitant); morphine, theophylline, quinine, riluzole, losartan, simvastatin, clofibrate, irinotecan, tadalafil. Increased risk of hepatoxicity with halothane, isoniazid. Absorption may be reduced by antacids. Isoniazid: May increase the risk of distal sensory neuropathy with stavudine. Increased renal clearance with zalcitabine in HIV infected patients. May increase the plasma concentration and elimination half-life with para-aminosalicylic acid. May cause hepatoxicity with general anaesthetics. Absorption may be reduced by antacids. Increased risk of CNS toxicity with ciclosporin. May reduce the plasma concentration of ketoconazole. May increase the plasma levels of theophylline. Inhibits the metabolism of anticonvulsants and benzodiazepines. Pyrazinamide: May antagonise the effects of probenecid and sulfinpyrazone.
CIMS Class
ATC Classification
J04AK01 - pyrazinamide ; Belongs to the class of other drugs used in the systemic treatment of tuberculosis.
J04AC01 - isoniazid ; Belongs to the class of hydrazides. Used in the systemic treatment of tuberculosis.
J04AB02 - rifampicin ; Belongs to the class of antibiotics. Used in the systemic treatment of tuberculosis.
Disclaimer: This information is independently developed by CIMS based on rifampicin + isoniazid + pyrazinamide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS 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 © 2021 CIMS. All rights reserved. Powered by CIMSAsia.com
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