Rifampicin / Ethambutol / Pyrazinamide / Isoniazid

Brands Names of Rifampicin / Ethambutol / Pyrazinamide / Isoniazid in Kenya

AkuriT-4, Aiveen Kenya Ltd.
Forecox Trac, Macleods Pharmaceuticals Limited
Rihaz E, Cosmos Limited
Rihide -E, Cosmos Limited
Rifafour -e- 275 tablet , sanofi-aventis Kenya
Rimstar 4-FDC , Sandoz Private Limited


Rifampicin inhibits the DNA-dependent RNA polymerase of sensitive bacterial strains, but without affecting the host enzymatic systems.

Isoniazid exerts a bactericidal effect mainly on rapidly growing populations of Mycobacterium tuberculosis. Its mechanism of action is probably based chiefly on inhibition of mycolic acid synthesis, mycolic acid being an important constituent of the mycobacterial cell wall.

Pyrazinamide: The exact mechanism of action is unknown. In vitro and in vivo studies have demonstrated that pyrazinamide is only active at a slightly acidic pH (pH 5.5).

Ethambutol: The mechanism of action is not fully known. It diffuses into mycobacteria and appears to suppress multiplication by interfering with RNA synthesis. It is effective only against mycobacteria that are actively dividing.


For initial treatment of tuberculosis according to World Health Organisation (WHO) guidelines.
Consideration should also be given to other official guidance on the appropriate use of anti-tuberculosis agents.


  • Hypersensitivity to rifamycins, isoniazid, pyrazinamide, ethambutol hydrochloride and/or to any of the excipients
  • A history of drug induced hepatitis and acute liver diseases regardless of its origin.
  • Porphyria.
  • Acute gouty arthritis.
  • Severe renal impairment (creatinine clearance < 30 ml/min)
  • Concomitant use with voriconazole and protease inhibitors, except ritonavir when given at full dose or 600 mg twice daily


Antacids reduce the bioavailability of rifampicin, isoniazid and ethambutol. To avoid this interaction, Rimstar 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.
Interactions with Rifampicin:
Rifampicin is the most potent inducer of the cytochrome P450 system (CYP450), notably of the two subfamilies CYP3A and CYP2C, which represent more than 80% of the isoenzymes of CYP450. Thus rifampicin may increase the metabolism of numerous concomitantly administered medicinal products which are metabolised, partially or totally, by these two subfamilies of CYP450. Moreover, rifampicin also induces UDP-glucuronyltransferase, another enzyme involved in the metabolism of several medicinal products. This can result in subtherapeutic plasma levels of the simultaneous administered medicinal products, with a decreased or even a loss of effect.
Use of the following medicinal products concomitantly with combination is contra-indicated: voriconazole and proteaseinhibitors, except ritonavir when given at full dose or 600 mg twice daily
Use of the following medicinal products concomitantly with this combination is not recommended: nevirapine, simvastatin, oral contraceptives and ritonavir (when given in low doses as a booster a marked reduction of plasma concentration might occur)
Use of the following medicinal products concomitantly with this Combination requires a precaution for use by monitoring specific parameters or through a clinical surveillance:
– Analgesics (e.g. methadone, narcotic analgesics, morphine, etoricoxib, rofecoxib)
– Antiarrhythmics (disopyramide, mexiletine, quinidine, propafenone, tocainide, lorcainide)
– Antibacterials (e.g. chloramphenicol, clarithromycin, dapsone, doxycycline, fluoroquinolones, telithromycin, linezolid, p-aminosalicylic acid)
– Anticoagulants (e.g. coumarins)
– Antidiabetics
– Antiepileptics (e.g. phenytoine, tiagabine, carbamazepine)
– Antifungals (e.g. fluconazole, itraconazole, ketoconazole, voriconazole, terbinafine)
– Antipsychotics (e.g. haloperidol, clozapine, aripiprazole)
– Antivirals (e.g. saquinavir, indinavir, efavirenz, amprenavir, nilfinavir, atazanavir, lopinavir, nevirapine, zidovudine)
– Anxiolytics and hypnotics (e.g. diazepam, benzodiazepines, buspirone, zopiclone, zolpidem, zaleplon)
– Atovaquone
– Barbiturates (e.g. hexobarbital)
– Beta-blockers (e.g. bisoprolol, propranolol, metoprolol, carvedilol (because of its uCosmos Limitedse in cardiac insufficiency and its low therapeutic margin in this indication))
– Calcium channel blockers (e.g. diltiazem, nifedipine, verapamil, nimodipine, isradipine, nicardipine, nisoldipine¸ amlodipine)
– Corticosteroids
– Cardiac glycosides (digitoxin, digoxin)
– Clofibrate
– Cytotoxics (e.g. imatinib, gefitinib, irinotecan)
– Diuretics (e.g. eplerenone)
– Oestrogen, progestogens
– Fexofenadine
– Hormone antagonists (antioestrogens e.g. tamoxifen, toremifene; gestrinone)
– Immunosuppressive agents (e.g. ciclosporin, sirolimus, tacrolimus, leflunomide, azathioprine)
– Losartan, imidapril, enalapril
– Praziquantel
– Quinine
– Selective 5-HT3 receptor antagonists (e.g. ondansetron, tropisetron)
– Statins metabolised by CYP 3A4 (e.g. simvastatin)
– Fluvastatin
– Systemic hormonal contraceptives
– Theophylline
– Thyroid hormone (e.g. levothyroxine)
– Tricyclic antidepressants (e.g. amitriptyline, nortriptyline)
Interactions with isoniazid:
Use of the following medicinal products concomitantly with this combination requires a precaution for use by monitoring specific parameters or through a clinical surveillance: halogenated volatile anaesthetics, glucocorticoids, ketoconazole, phenytoin, pyrazinamide, stavudine, carbamazepine, benzodiazepines, ethosuximide, theophylline.
Interactions with pyrazinamide:
Use of the following medicinal products concomitantly with  this combination requires a precaution for use by monitoring specific parameters or through a clinical surveillance: probenecid, sulfinpyrazon.
Rifampicin may reduce the effectiveness of oral contraceptives and patients treated with Rimstar should use a non-hormonal method of contraception.
Oral typhoid vaccine might be inactivated by concomitant antibiotic administration.
Isoniazid is an inhibitor of monoamine oxidase (MAO) and diamine oxidase (DAO), which can reduce tyramine and histamine metabolism, causing symptoms such as headache, sweating, palpitations, flushing, and hypotension. Patients should therefore be advised against ingesting foods rich in tyramine and/or histamine, such as cured meat, some cheeses (e.g. matured cheeses), wine, beer and some fish (e.g. tuna, mackerel, salmon).
Rifampicin can delay the biliary excretion of contrast media during gallbladder radiographic examination.
Microbiological methods used to determinate folic acid and cyanocobalamine (vitamin B12) plasma concentrations can not be used during rifampicin treatment as rifampicin is in competition with bilirubin and BSP. To avoid false positive reactions, BSP test should be carried out the morning before rifampicin administration.



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 foetus.
Rifampicin, isoniazid, pyrazinamide and ethambutol pass into the breast milk, but no undesirable 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 and ethambutol.


Undesirable effects of rifampicin which may occur during continuous daily or intermittent therapy
Blood and lymphatic system disorders:
Transient leucopenia, eosinophilia, agranulocytosis. Thrombocytopenia and thrombocytopenic purpura are encountered more frequently with intermittent therapy than with continuous daily treatment, during which they occur only in very care cases.
Endocrine disorders
Rare: Menstrual disturbances (in extreme cases amenorrhoea); induction of crisis in Addison patients
Psychiatric disorders
Rare: Mental confusion, psychosis.
Nervous system disorders:
Common: Tiredness, drowsiness, headache, light-headedness, dizziness
Rare: Ataxia, muscular weakness, myopathy
Eye disorders:
Common: Reddening of the eyes, permanent discolouration of soft contact lenses
Rare: Visual disturbances, Severe signs and symptoms, such as e.g. exudative conjunctivitis
Gastrointestinal disorders:
Common: Anorexia, nausea, abdominal pain, bloatedness
Rare: Vomiting or diarrhoea, isolated occurrences of erosive gastritis and pseudomembranous colitis, pancreatitis
Skin and subcutaneous tissue disorders:
Common: Flushing, itching with or without skin rash, urticaria
Rare: Severe skin reactions such as Stevens-Johnson syndrome and generalised hypersensitivity reactions, e.g. exfoliative dermatitis, Lyell’s syndrome and pemphigoid reactions
Hepatobiliary disorders:
Common: Asymptomatic increase in liver enzymes
Rare: Hepatitis or jaundice, induction of porphyria
Renal and urinary disorders
Rare: Elevations of BUN (blood urea nitrogen) and serum uric acid have been reported. Acute renal failure due to haemoglobinuria, haematuria, interstitial nephritis, glomerulonephritis and tubular necrosis has been reported.
General disorders and administration site conditions:
Common: Reddish discoloration of body fluids and secretions such as e.g. urine, sputum, lacrimal fluid, faeces, saliva and sweat.
Rare: Collapse, shock, oedema
Undesirable effects of isoniazid
Blood and lymphatic system disorders:
Rare: Eosinophilia, thrombocytopenia, anaemia (haemolytic, sideroblastic)
Endocrine disorders:
Rare: soniazid may interfere with liver metabolism of several hormones, resulting in menstrual disturbances, gynaecomastia, Cushing syndrome, pubertas praecox, and difficult controllable diabetes, hyperglycaemia
Psychiatric disorders:
Rare: Psychoses, hyperactivity, euphoria, insomnia
Nervous system disorders
Common: Peripheral neuropathy (dose dependent and more common in undernourished patients, alcoholics, slow acetylators and diabetics), usually preceded by paresthesias of feet and hands
Rare: Damage to the optic nerve (see section 4.4), convulsions, dizziness, light-headedness, headache, toxic encephalopathy. High doses may increase seizure frequency in epileptics
Undesirable effects of pyrazinamide
Blood and lymphatic system disorders
Rare:Thrombocytopenia, sideroblastic anaemia, undesirable effects on blood clotting mechanisms, splenomegaly
Gastrointestinal disorders
Common:Nausea, vomiting, anorexia, abdominal pain
Hepatobiliary disorders
Common:Moderate and transient rises in serum transaminase level during the early phase of treatment Porphyria
Rare:Severe hepatotoxicity appears to be related to dose; hepatomegaly, jaundice
Renal and urinary disorders
Common:Hyperuricaemia (often asymptomatic), gout requiring treatment Rare:Interstitial nephritis, dysuria
General disorders and administration site conditions
Common: Allergic and other reactions, like mild arthalgia and myalgia
Rare: Allergic and other reactions, like skin rash, photosensitivity, urticaria, pruritus, fever, acne
Undesirable effects of Ethambutol
Blood and lymphatic system disorders
Rare: Thrombocytopenia, leucopenia
Psychiatric disorders
Nervous system disorders
Uncommon: Dizziness, disorientation, confusion, headache, malaise
Rare: Peripheral neuritis (numbness, tingling, burning pain, or weakness in hands or feet)
Eye disorders
Rare: Dose-dependent retrobulbar optic neuritis (blurred vision, eye pain, red-green colour blindness, loss of vision)
Gastrointestinal disorders
Uncommon: Abdominal pain, loss of appetite, nausea and vomiting, anorexia
Skin and subcutaneous tissue disorders
Uncommon: Pruritus, urticaria, rash
Renal and urinary disorders
Uncommon: Hyperuricaemia that might result in acute gouty arthritis (chills; pain and swelling of joints, especially big toe, ankle, or knee; tight, hot skin over affected joints)
General disorders and administration site conditions
Rare: Hypersensitivity (skin rash, fever, joint pain), anaphylactic reactions

Clinical | Pharmacokinetic data

Pregnancy Category: C :
Routes of Administration: Oral
Bioavailability: Not Available
Protein Binding: Not Available
Metabolosim: Not Available
Onset of Action: N/A
Elimination Half life: Not Available
Excretion: Not Available

Legal Status | Dosage forms & Strengths

Prescription Category:
Prescription only Medicine (POM) , ℞-only
Narcotic Drugs and Psychotropic Substances (Control ) Act Schedule:
This Drug is not Subject to DDA drugs Act
Dosage Forms | Strengths:

Drug Indentifiers:

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