Skip to content
ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Antitubercular fixed-dose combination (RHZ) Pregnancy: SPC 4.6, verbatim: 'At very high doses in animals rifampicin has been shown to have teratogenic effects. There are no well controlled studies with Rifater in pregnant women. Although rifampicin has been reported to cross the placental barrier and appear in cord blood, the effect of rifampicin, alone or in combination with other antituberculosis drugs, on the human fetus is not known. When administered during the last few weeks of pregnancy, rifampicin may cause post-natal haemorrhages in the mother and infant, for which treatment with Vitamin K1 may be indicated.' For isoniazid: 'in both rats and rabbits, isoniazid may exert an embryocardial effect when administered orally during pregnancy, although no isoniazid-related congenital anomalies have been found in reproduction studies in mammalian species'. Conclusion in the SPC: 'Rifater should be used in pregnant women or in women of child-bearing potential only if the potential benefit justifies the potential risk to the foetus.' BREAST-FEEDING: 'Rifampicin, isoniazid and pyrazinamide are excreted in breast milk and infants should not be breast-fed by a patient receiving Rifater unless in the physician's judgement the potential benefit to the patient outweighs the potential risk to the infant.' In breast-fed infants of mothers taking isoniazid there is a theoretical risk of convulsions and neuropathy from vitamin B6 deficiency; the SPC advises monitoring and considering prophylactic pyridoxine for both mother and infant.

Rifampicin with isoniazid and pyrazinamide

Brand names: Rifater

A four-drug oral fixed-dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol used in the intensive (initial) phase of tuberculosis treatment, combining the agents in one tablet to aid adherence.

Adult dose

Dose: Weight-banded tablet count of the fixed combination: 3 tablets daily if body weight is less than 40 kg; 4 tablets if 40-49 kg; 5 tablets if 50-64 kg; 6 tablets if 65 kg or more. Product strength is pinned by the licensed name 'Rifater 50mg/120mg/300mg Tablets'; the SPC quantifies what those counts deliver for each of the three components - 9-12 mg/kg rifampicin (RAMP), 4-5 mg/kg isoniazid (INH) and 23-30 mg/kg pyrazinamide (Z).
Route: Oral. SPC method of administration: 'For oral administration.' Posology: 'Rifater should be given as a single dose and preferably on an empty stomach at least 30 minutes before a meal, or 2 hours after a meal to ensure rapid and complete absorption.'
Frequency: Once daily, on a daily continuous basis, throughout the 2-month initial intensive phase. SPC: 'Rifater is recommended in the initial intensive phase of the short-course treatment of pulmonary tuberculosis. During this phase, which lasts for 2 months, Rifater should be administered on a daily continuous basis.'
SCOPE: this covers the page's primary indication and route only - the oral fixed-dose combination in the 2-month intensive phase of pulmonary TB in adults. VERBATIM SPC 4.2 wording for the dose: 'Each Rifater tablet contains isoniazid (INH), pyrazinamide (Z) and rifampicin (RAMP) in such a ratio that the administration of 9 - 12 mg/kg RAMP, 4 - 5 mg/kg INH and 23 - 30 mg/kg Z can be achieved by giving 3 tablets daily to patients weighing less than 40 kg, 4 tablets to patients weighing 40 - 49 kg, 5 tablets to patients weighing 50 - 64 kg and 6 tablets to patients weighing 65 kg or more.' NO MAXIMUM DOSE is stated anywhere in the fetched SPC - the 6-tablet band is the top weight band, not a labelled ceiling, so maxDose is left empty rather than inferred. COMPANION DRUGS: 'The concomitant administration of ethambutol or intramuscular streptomycin over the same period of time is advised.' CONTINUATION PHASE: 'Once the initial intensive phase of treatment has been completed treatment can be continued with the combination rifampicin-isoniazid (Rifinah) always on a daily basis.' ELDERLY: 'Caution should be exercised in such patients, in view of the possible decrease of the excretory function of the kidney and of the liver.' SUPERVISION: 'Rifater should be given under the supervision of a respiratory or other suitably qualified physician.' The fetched SPC gives no missed-dose, renal-dosing or hepatic-dosing instruction.

Paediatric dose

Route: Oral
NO PAEDIATRIC DOSE IS PUBLISHED HERE. SPC 4.2 'Children', verbatim: 'The ratio of the three drugs in Rifater may not be appropriate in children (eg higher mg/kg doses of INH are usually given in children than in adults). Rifater can be used only in special cases, after careful consideration of the mg/kg dose of each component.' The adult regimen is weight-banded by tablet count, not a per-kg per-dose figure, so no weight-calculator value can be derived from it. For anyone under 18, dose each of the three components separately against a children's formulary and current national TB guidance.

Dose adjustments

Renal

No renal dose adjustment is stated in the fetched SPC. The only renal-related statement is under 'Use in the elderly': 'Caution should be exercised in such patients, in view of the possible decrease of the excretory function of the kidney and of the liver.' Baseline serum creatinine is required before treatment (section 4.4). Verify against the full SPC and current TB guidance before dosing in renal impairment.

Hepatic

No hepatic dose adjustment is stated in the fetched SPC; instead, jaundice is an absolute contraindication (section 4.3: contraindicated 'in the presence of jaundice'). Section 4.4: 'Each of these drugs has been associated with liver dysfunction. All tuberculosis patients should have pre-treatment measurements of liver function.' Note the fetched 4.4 text is truncated at the source-fetch limit, so further hepatic guidance may exist in the full SPC.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to any one of the components of the combination or to any of the excipients (SPC 4.3)
  • In the presence of jaundice (SPC 4.3)
  • Concurrent treatment with the combination of saquinavir/ritonavir (SPC 4.3)
  • Medicines strongly affected by rifampicin's potential to induce drug metabolizing enzymes and transporters, specifically named in SPC 4.3: lurasidone; sofosbuvir, daclatasvir and telaprevir; cabotegravir, fostemsavir and lenacapavir
  • From the US single-agent rifampicin label (cross-check only, may differ from UK): also contraindicated with atazanavir, darunavir, fosamprenavir, saquinavir, tipranavir, and with praziquantel
  • The fetched SPC 4.3 text ends at the source-fetch limit - treat this list as partial and check the full SPC

Side effects

  • Hepatobiliary (rifampicin, frequency not known): drug-induced liver injury including fatal cases, especially when used in combination with other anti-tuberculosis drugs; hepatitis; hyperbilirubinaemia
  • Blood (common): thrombocytopenia with or without purpura, usually associated with intermittent therapy, reversible if the drug is stopped as soon as purpura occurs. Uncommon: leukopenia. Not known: thrombotic microangiopathy including TTP/HUS, disseminated intravascular coagulation, eosinophilia, agranulocytosis, haemolytic anaemia, vitamin K dependent coagulation disorders
  • Nervous system (common): headache, dizziness. Not known: 'Cerebral haemorrhage and fatalities have been reported when rifampicin administration has been continued or resumed after the appearance of purpura'
  • Gastrointestinal (common): nausea, vomiting. Uncommon: diarrhoea. Not known: abdominal discomfort, tooth discolouration (which may be permanent), pseudomembranous colitis
  • Skin (not known): erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, acute generalized exanthematous pustulosis, pruritus, urticaria, allergic dermatitis, pemphigoid, sweat discoloration
  • Discoloration of body fluids: tear discolouration, sputum discoloured, chromaturia, sweat discoloration
  • Metabolic (not known): decreased appetite, hyperuricaemia
  • Renal (not known): acute kidney injury usually due to renal tubular necrosis or tubulointerstitial nephritis
  • General (very common): pyrexia, chills
  • Vascular / immune (not known): shock, flushing, vasculitis, bleeding, anaphylactic reaction; endocrine: adrenal insufficiency in patients with compromised adrenal function
  • Respiratory (not known): dyspnoea, wheezing, interstitial lung disease including pneumonitis
  • The fetched SPC 4.8 lists rifampicin's table first and is truncated at the source-fetch limit before the isoniazid and pyrazinamide tables - the isoniazid and pyrazinamide adverse-reaction lists were NOT retrieved

Monitoring

  • Before treatment: 'All tuberculosis patients should have pre-treatment measurements of liver function.' Adults starting Rifater 'should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count and a platelet count (or estimate)' (SPC 4.4)
  • During treatment: 'Patients should be seen at least monthly during therapy and should be questioned specifically about symptoms associated with adverse reactions' (SPC 4.4)
  • If there is no pre-existing liver disease and pre-treatment liver function was normal, 'liver function tests need only be repeated if fever, vomiting, jaundice or other deterioration in the patient's condition occur' (SPC 4.4)
  • Patients older than 35 years: 'a transaminase measurement should be obtained at baseline and at least monthly during therapy in this age group', because of the higher frequency of isoniazid-associated hepatitis (SPC 4.4)
  • Watch for severe systemic hypersensitivity including DRESS - 'early manifestations of hypersensitivity, such as fever, lymphadenopathy or biological abnormalities (including eosinophilia, liver abnormalities) may be present even though rash is not evident' (SPC 4.4)
  • Watch for severe cutaneous adverse reactions (SJS, TEN, AGEP): 'At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions... Most of these reactions occurred within 2 days to 2 months after treatment initiation.' Withdraw immediately if suspected (SPC 4.4)

Clinical monograph

How it works

Rifampicin inhibits bacterial RNA polymerase, isoniazid blocks mycolic acid synthesis, and pyrazinamide is active against semi-dormant bacilli in acidic intracellular conditions, together targeting different mycobacterial populations and reducing the emergence of resistance.

Prescribing in practice

  • All three components are potentially hepatotoxic, so check baseline liver function, monitor during treatment, and counsel patients to report symptoms of hepatitis promptly.
  • Rifampicin is a potent enzyme inducer that reduces the efficacy of many drugs including hormonal contraception, so co-medication must be reviewed; this combination is typically used with ethambutol where indicated.
  • Pyridoxine is co-prescribed to prevent isoniazid-induced peripheral neuropathy, and pyrazinamide may raise serum urate and precipitate gout.

Monitoring

Monitor liver function and clinical wellbeing during treatment, and be alert to hyperuricaemia from the pyrazinamide component.

Counselling the patient

  • Take the tablets as a single daily dose, usually before food, and complete the entire course.
  • Rifampicin turns urine, tears and other body fluids orange-red and can permanently stain soft contact lenses.
  • Report promptly any yellowing of the skin or eyes, nausea, loss of appetite or joint pain.

Evidence & guidelines

Fixed-dose combination therapy is recommended in NICE tuberculosis guidance to improve adherence and limit acquired drug resistance during the intensive phase.

Reference: NICE NG33; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways