Usage
Capreomycin sulfate is an antimycobacterial agent indicated for the treatment of pulmonary tuberculosis (TB) caused by capreomycin-susceptible strains of Mycobacterium tuberculosis, when primary agents (isoniazid, rifampin, ethambutol, aminosalicylic acid, and streptomycin) have been ineffective or cannot be used due to toxicity or the presence of resistant tubercle bacilli. It is classified as a cyclic polypeptide antibiotic.
Capreomycin inhibits protein synthesis in susceptible M. tuberculosis strains, ultimately leading to bacterial cell death. It works by binding to the bacterial ribosome, specifically to the 30S subunit, and interfering with the process of translation.
Alternate Names
Capreomycin is also known as Capastat Sulfate (brand name).
How It Works
Pharmacodynamics: Capreomycin exerts its bactericidal effect by inhibiting protein synthesis in susceptible mycobacteria. It binds to the 30S ribosomal subunit, interfering with the formation of the initiation complex and causing misreading of messenger RNA. This ultimately disrupts protein synthesis and leads to bacterial cell death.
Pharmacokinetics:
- Absorption: Capreomycin is not absorbed orally and must be administered intramuscularly (IM) or intravenously (IV).
- Distribution: After IM or IV administration, capreomycin distributes widely into extracellular fluids but has limited penetration into cerebrospinal fluid.
- Metabolism: Capreomycin is not significantly metabolized.
- Excretion: Primarily eliminated unchanged by the kidneys through glomerular filtration. The elimination half-life is approximately 3-6 hours in patients with normal renal function.
Elimination Pathways: Renal excretion is the primary route of elimination.
Dosage
Standard Dosage
Adults:
- Initial: 1 g IM/IV daily (not to exceed 20 mg/kg/day) for 60-120 days.
- Maintenance: 1 g IM/IV 2-3 times/week. Total treatment duration for tuberculosis should be 12-24 months.
Children:
<15 years old and <40 kg: 15-30 mg/kg IV/IM daily (maximum 1 g/day) for 2-4 months followed by 15-30 mg/kg twice weekly (maximum 1 g/day).>15 years old and >40 kg: 15 mg/kg IV/IM daily (maximum 1 g/day) for 2-4 months followed by 15 mg/kg 2-3 times/week (maximum 1 g/dose).- Capreomycin is always used in conjunction with other antitubercular agents in children.
Special Cases:
- Elderly Patients: Dosage reduction may be necessary based on renal function.
- Patients with Renal Impairment: Dose adjustment is necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: No specific dose adjustments are typically needed as capreomycin is primarily renally eliminated. However, close monitoring is recommended.
- Patients with Comorbid Conditions: Caution advised in patients with pre-existing hearing impairment.
Clinical Use Cases
Capreomycin is specifically indicated for drug-resistant pulmonary tuberculosis. Its use in other clinical settings (intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations) is not established or recommended.
Dosage Adjustments
Dose modifications are required for patients with renal impairment.
Side Effects
Common Side Effects:
- Nephrotoxicity (e.g., elevated BUN, creatinine)
- Ototoxicity (hearing loss, tinnitus, vertigo)
- Electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia)
- Pain and induration at injection site
Rare but Serious Side Effects:
- Renal failure
- Permanent hearing loss
- Severe allergic reactions (rash, itching, swelling, difficulty breathing)
Long-Term Effects:
- Chronic kidney disease
- Permanent hearing impairment
Adverse Drug Reactions (ADR):
- Renal failure
- Severe allergic reactions
Contraindications
- Hypersensitivity to capreomycin
- Pre-existing auditory or vestibular dysfunction
Drug Interactions
Numerous drug interactions are possible with capreomycin, particularly with other nephrotoxic or ototoxic drugs such as aminoglycosides (amikacin, gentamicin, kanamycin, tobramycin), polymyxins (colistin, polymyxin B), and vancomycin. Neuromuscular blocking agents like atracurium, cisatracurium, pancuronium, rocuronium, and vecuronium can have additive effects with capreomycin, increasing the risk of respiratory depression.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C
- Fetal risks include teratogenicity, particularly in the first trimester.
- Excretion in breast milk: Unknown. Caution advised when administered to nursing mothers.
Drug Profile Summary
- Mechanism of Action: Inhibits protein synthesis in susceptible mycobacteria by binding to the 30S ribosomal subunit.
- Side Effects: Nephrotoxicity, ototoxicity, electrolyte disturbances, injection site reactions, allergic reactions.
- Contraindications: Hypersensitivity to capreomycin, pre-existing auditory or vestibular dysfunction.
- Drug Interactions: Aminoglycosides, polymyxins, vancomycin, neuromuscular blocking agents.
- Pregnancy & Breastfeeding: Category C; caution advised.
- Dosage: Adults: 1 g IM/IV daily for 60-120 days followed by 1 g IM/IV 2-3 times/week; Pediatric dosing based on weight, maximum 1g/day. Adjustments needed for renal impairment.
- Monitoring Parameters: Renal function (BUN, creatinine), serum electrolytes (potassium, magnesium, calcium), audiometry.
Popular Combinations
Capreomycin is typically used in combination with other second-line anti-TB drugs, tailored to the individual patient’s resistance profile. These may include ethionamide, cycloserine, para-aminosalicylic acid (PAS), fluoroquinolones, and bedaquiline or linezolid in some cases.
Precautions
- Renal function, hearing, and electrolyte monitoring are crucial.
- Pre-existing renal or auditory impairment requires careful consideration and dose adjustments.
- Use with caution in pregnant or breastfeeding women.
- Safety and efficacy in children have not been fully established.
FAQs
Q1: What is the recommended dosage for Capreomycin?
A: Adults: 1 g IM/IV daily for 60-120 days, followed by 1 g IM/IV 2-3 times a week. Children: dosing is weight-based (see Dosage section above).
Q2: What are the most important side effects of Capreomycin?
A: Nephrotoxicity and ototoxicity are the most significant adverse effects. Monitoring renal function (BUN, creatinine), serum electrolytes, and hearing (audiometry) is essential.
Q3: Is Capreomycin safe to use during pregnancy?
A: Capreomycin is a Pregnancy Category C drug. It should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
Q4: What are the contraindications for using Capreomycin?
A: Hypersensitivity to capreomycin and pre-existing auditory or vestibular dysfunction are absolute contraindications.
Q5: How does Capreomycin interact with other medications?
A: Capreomycin can interact with other nephrotoxic or ototoxic drugs, increasing the risk of adverse effects. It can also interact with neuromuscular blocking agents, leading to increased risk of respiratory depression.
Q6: What monitoring parameters are essential when administering Capreomycin?
A: Monitor renal function (BUN, creatinine), serum electrolytes (potassium, magnesium, calcium), and audiometry are essential.
Q7: How is Capreomycin administered?
A: Capreomycin can be administered IM or by slow IV infusion over 60 minutes.
Q8: What is the mechanism of action of Capreomycin?
A: Capreomycin inhibits protein synthesis in susceptible mycobacteria by binding to the 30S ribosomal subunit.
Q9: Can Capreomycin be used in children?
A: Yes, but dosing is weight-based, and safety and efficacy have not been fully established in children. It should be used with caution and in conjunction with other antitubercular agents.
Q10: Is there a specific antidote for Capreomycin overdose?
A: No specific antidote exists for capreomycin overdose. Treatment is primarily supportive and focuses on managing symptoms and complications. Hemodialysis may be beneficial in cases of severe nephrotoxicity.
