Rifampicin + isoniazid + pyrazinamide

Should be taken on an empty stomach. Avoid antacids w/in 1 hr of intake.

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.

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).

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]).

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.

Anti-TB Agents

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.