Rifcin

Approved Indications:

• Tuberculosis (TB):
• Active pulmonary and extrapulmonary TB in combination with other antitubercular drugs.
• Latent TB infection (LTBI) in combination therapy (e.g., with isoniazid or as monotherapy when isoniazid is contraindicated).
• Leprosy (Hansen’s Disease):
• Multibacillary and paucibacillary leprosy as part of multidrug therapy.
• Meningococcal Prophylaxis:
• Prophylaxis of Neisseria meningitidis carriers and close contacts.
• Haemophilus influenzae Prophylaxis:
• Prophylaxis in households with children under 4 years who are at risk.
• Staphylococcal Infections (off-label):
• In combination therapy for prosthetic joint infections or endocarditis caused by Staphylococcus aureus.
• Mycobacterium avium complex (MAC):
• Part of combination therapy in HIV-positive patients.

Route: Oral; IV (in hospital setting when oral route not possible)

Adults:

• Active TB:
  600 mg once daily (10 mg/kg/day; max 600 mg/day) for 6–9 months with other anti-TB drugs.
• Latent TB Infection:
  600 mg once daily for 4 months (monotherapy) or 3 months with isoniazid.
• Leprosy:
  600 mg once monthly supervised dose (multidrug regimen).
• Meningococcal Prophylaxis:
  600 mg twice daily for 2 days.
• H. influenzae Prophylaxis:
  600 mg once daily for 4 days.

Pediatrics:

• TB: 10–20 mg/kg/day (max 600 mg/day).
• Meningococcal Prophylaxis:
• 10 mg/kg (children ≥1 month) twice daily for 2 days.
• 5 mg/kg (infants <1 month) twice daily for 2 days.

Elderly:
Same as adult dose unless contraindicated due to hepatic function.

Renal Impairment:
No dose adjustment usually required.

Hepatic Impairment:
Use with caution. Monitor liver function closely. Dose reduction may be necessary.

Rifampicin inhibits bacterial DNA-dependent RNA polymerase by binding to its β-subunit. This blocks RNA synthesis and, consequently, protein production, resulting in bactericidal activity. Its action is most pronounced against rapidly multiplying organisms such as Mycobacterium tuberculosis and other Gram-positive and some Gram-negative bacteria. Rifampicin penetrates well into tissues and macrophages, reaching intracellular pathogens.

• Absorption:
  Rapidly absorbed orally; peak plasma concentration in 2–4 hours.
• Bioavailability:
  ~70% (decreased with food intake).
• Distribution:
  Widely distributed including CSF (especially with inflamed meninges), lungs, liver, and bone. High tissue penetration.
• Protein Binding:
  ~80%.
• Metabolism:
  Hepatic via deacetylation (active metabolite).
• Half-life:
  2–5 hours (can decrease with enzyme induction).
• Excretion:
  Primarily via bile into feces (60–65%); some renal excretion (~30%).

• Pregnancy:
  Category C (US FDA). Use only if benefits outweigh risks. Rifampicin may increase risk of hemorrhagic disease in the newborn; vitamin K supplementation recommended near term.
• Lactation:
  Excreted in breast milk in low concentrations. Generally considered compatible with breastfeeding, but monitor infant for potential adverse effects (e.g., GI upset, orange discoloration of body fluids).

• Primary Class: Antitubercular Agent
• Subclass: Rifamycin Derivative (First-line)

• Known hypersensitivity to rifampicin or other rifamycins
• Concomitant use with certain antiretrovirals (e.g., protease inhibitors) or other drugs highly metabolized by CYP enzymes, unless benefits outweigh risks
• Severe hepatic dysfunction (if alternative unavailable)

• Hepatotoxicity:
  Monitor LFTs before and during therapy; discontinue if significant liver dysfunction occurs.
• Discoloration of Body Fluids:
  May cause orange-red discoloration of urine, sweat, tears, and contact lenses.
• Drug Interactions:
  Strong inducer of CYP450 enzymes – reduces efficacy of many drugs.
• Thrombocytopenia and Hemolytic Anemia:
  Reported rarely with intermittent therapy; avoid such regimens unless strictly supervised.
• Flu-like Syndrome:
  Common with intermittent dosing – avoid unless essential.
• Use in Hepatic Impairment:
  Increased risk of hepatotoxicity – monitor closely.
• Superinfection Risk:
  Prolonged use may result in fungal or bacterial superinfection.

Common:

• GI: Nausea, vomiting, abdominal discomfort, diarrhea
• Hepatic: Elevated transaminases, bilirubin
• Dermatologic: Rash, pruritus
• Discoloration: Orange-red urine, saliva, tears

Serious:

• Hepatotoxicity
• Acute renal failure (intermittent use)
• Hemolytic anemia, thrombocytopenia
• Hypersensitivity reactions (fever, eosinophilia)

Rare:

• Flu-like syndrome
• Pseudomembranous colitis

CYP450 Induction (especially CYP3A4, CYP2C9, CYP2C19):

• ↓ Effectiveness of:
  Warfarin, oral contraceptives, antiretrovirals (protease inhibitors, NNRTIs), antifungals, corticosteroids, digoxin, cyclosporine, beta-blockers, antiepileptics (e.g., phenytoin), sulfonylureas.

↑ Hepatotoxicity Risk with:
Isoniazid, pyrazinamide, alcohol.

Other Interactions:

• May reduce serum levels of certain antibiotics (e.g., doxycycline).
• Avoid concomitant use with nevirapine or ritonavir unless no alternatives exist.

• WHO and CDC continue to recommend rifampicin as a core drug in first-line TB therapy.
• Updated regimens for short-course TB prevention (e.g., 4 months rifampicin-only regimen) endorsed by WHO.
• Warning: Increased scrutiny over drug interactions with newer antiretrovirals; monitoring required.
• EMA added recommendations for careful liver function monitoring in 2023 TB guidelines.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Light: Protect from light.
• Humidity: Store in a dry place; keep container tightly closed.
• Handling: Oral suspension should be shaken well before use.
• IV Formulations: Reconstituted solution should be used within specified time and refrigerated if needed.