Makindo Medical Notes

💉 Capreomycin is a second-line injectable antituberculous agent used primarily for multidrug-resistant tuberculosis (MDR-TB). ⚠️ It is both nephrotoxic and ototoxic — careful renal, vestibular, and auditory monitoring are essential. Always 🔗 check the BNF entry before prescribing.

🧠 About

• Capreomycin is a cyclic polypeptide antibiotic produced by *Streptomyces capreolus*.
• It is reserved for the management of MDR-TB or cases resistant to first-line agents (e.g., isoniazid and rifampicin).
• Mechanistically and clinically, it behaves similarly to the aminoglycosides (e.g., amikacin, kanamycin) but is chemically distinct.
• It must be administered by deep intramuscular injection and only under specialist supervision.

⚙️ Mode of Action

• Binds to the bacterial 70S ribosome complex, interfering with protein synthesis by inhibiting translation and peptide chain elongation.
• Bacteriostatic or bactericidal depending on concentration and organism susceptibility.
• Effective primarily against *Mycobacterium tuberculosis*, including many drug-resistant strains.

💊 Indications & Dosing

• Multidrug-Resistant Tuberculosis (MDR-TB):
• Initial intensive phase: 1 g IM daily (or ≤20 mg/kg/day) for 60–120 days.
• Continuation phase: 1 g IM two to three times per week thereafter.
• Duration of therapy is typically several months as part of a multidrug regimen including ethionamide, cycloserine, and PAS.
• Renal function must be checked regularly and dosing intervals extended if renal impairment develops.

🧪 Pharmacology

• Class: Cyclic peptide antibiotic (non-aminoglycoside).
• Absorption: Poor oral absorption; given IM only.
• Distribution: Widely distributed in extracellular fluids; poor CSF penetration.
• Excretion: Renal, largely unchanged — accumulation occurs with renal dysfunction.
• Half-life: ~4–6 hours (prolonged in renal impairment).

🤝 Interactions

• Other nephrotoxic or ototoxic agents (e.g., aminoglycosides, vancomycin, amphotericin B, loop diuretics) → greatly increase toxicity risk.
• Neuromuscular blockers → enhanced blockade and respiratory depression possible.
• Monitor renal function and auditory symptoms if co-administered with other TB drugs (e.g., cycloserine, ethionamide).

⚠️ Cautions

• Renal impairment: dose reduction or increased dosing interval required.
• Auditory and vestibular toxicity: perform baseline and periodic audiometry and vestibular function tests.
• Electrolyte monitoring: hypokalaemia, hypomagnesaemia, and hypocalcaemia may occur due to renal tubular toxicity.
• Use only in specialist TB centres with facilities for close laboratory and clinical supervision.

⛔ Contraindications

• Hypersensitivity to capreomycin or other peptide antibiotics.
• Significant pre-existing renal impairment or auditory/vestibular damage.
• Pregnancy — risk of fetal ototoxicity and nephrotoxicity; use only if benefits outweigh risks.

💢 Side Effects

• Renal toxicity: raised creatinine, reduced urine output, electrolyte disturbances (↓K⁺, ↓Mg²⁺).
• Ototoxicity: tinnitus, hearing loss, vertigo — may be irreversible.
• Neuromuscular blockade: rare but can cause respiratory paralysis (especially if co-administered with anaesthetics or muscle relaxants).
• Injection-site pain and sterile abscess formation possible.
• Fever, eosinophilia, rash, and hepatotoxicity reported.

🧠 Clinical Pearls

• Capreomycin is typically reserved for MDR-TB regimens where resistance to aminoglycosides is present.
• Therapeutic Drug Monitoring (TDM) may help optimise dosing and reduce toxicity.
• Always avoid concurrent ototoxins and ensure patient hydration.
• Hearing loss or renal dysfunction mandates immediate review and possible cessation.
• Resistance can develop rapidly if used as monotherapy — always combine with other active anti-TB drugs.

📚 References

• BNF: Capreomycin
• World Health Organization (WHO) MDR-TB Guidelines, 2023.
• UpToDate: “Treatment of drug-resistant tuberculosis in adults.”
• Joint Tuberculosis Committee of the BTS: Management of Multi-Drug Resistant Tuberculosis (UK, 2022).