Rifampicin + Isoniazid

Generic Details

Generic Name

rifampicin-isoniazid

Other Names

  • Rifamate
  • Rifinah

Drug Class

  • Antituberculosis Agent
  • Rifamycin
  • Hydrazide

Chemical Formula

C43H58N4O12 (Rifampicin), C6H7N3O (Isoniazid)

Molecular Weight

822.94 g/mol (Rifampicin), 137.14 g/mol (Isoniazid)

Mechanism of Action

  • Rifampicin: Inhibits DNA-dependent RNA polymerase in bacterial cells, preventing transcription.
  • Isoniazid: Inhibits mycolic acid synthesis, a vital component of the bacterial cell wall.

Indications

  • Treatment of active tuberculosis
  • Latent tuberculosis infection in high-risk patients

Common Dosage Forms

  • Capsule
  • Tablet

Typical Dosage

  • Rifampicin 600 mg/Isoniazid 300 mg once daily

Pediatric Dosage

  • Rifampicin 10-20 mg/kg/Isoniazid 10-15 mg/kg once daily

Geriatric Dosage

  • Adjust dosage based on renal and hepatic function; typically, start with adult dosing.

Side Effects

  • Hepatotoxicity
  • Peripheral neuropathy
  • Nausea and vomiting
  • Fever
  • Skin rashes
  • Thrombocytopenia
  • Flu-like symptoms

Contraindications

  • Severe liver disease
  • Hypersensitivity to rifampicin, isoniazid, or any of the excipients

Pregnancy Category

  • Category C (USA)
  • Consult local guidelines for usage in pregnancy

Lactation Safety

  • Limited data available; use with caution during breastfeeding.

Drug Interactions

  • Oral contraceptives (decreased effectiveness)
  • Warfarin (reduced anticoagulant effect)
  • Antiretroviral drugs (reduced efficacy of protease inhibitors and NNRTIs)
  • Phenytoin (increased levels and toxicity of phenytoin)

Overdose Symptoms

  • Nausea
  • Vomiting
  • Confusion
  • Hepatitis
  • Seizures

Antidote for Overdose

  • Supportive treatment
  • Pyridoxine (for isoniazid toxicity)
  • Activated charcoal

Storage Conditions

  • Store below 25°C (77°F)
  • Protect from light and moisture

Pharmacokinetics

  • Absorption: Well absorbed orally, with peak plasma concentrations in 2-4 hours.
  • Distribution: Widely distributed in body tissues and fluids, including cerebrospinal fluid.
  • Metabolism: Rifampicin is metabolized in the liver to an active metabolite; isoniazid is acetylated in the liver.
  • Excretion: Rifampicin: primarily excreted in bile; Isoniazid: excreted in urine as unchanged drug and metabolites.

Precautions

  • Monitor liver function tests regularly.
  • Use with caution in patients with liver disease or alcoholism.
  • Patients should avoid alcohol during treatment.

Warnings

  • Hepatotoxicity: Serious and sometimes fatal hepatotoxicity may occur; regular monitoring is required.
  • Peripheral neuropathy: May occur, especially in malnourished patients; co-administration of pyridoxine may reduce this risk.

Others

  • Patients may experience orange-red discoloration of body fluids such as urine, sweat, and tears, which is harmless but may stain clothing.