Capreomycin Sulfate

(USAN, rINNM)
Synonyms: 34977; Capreomycin Sulphate (BANM); Capréomycine, Sulfate de; Capreomycini Sulfas; Capromycin Sulphate; Sulfato de capreomicina.
Cyrillic synonym: Капреомицина Сульфат.

💊 Chemical information

CAS — 11003-38-6 (capreomycin); 1405-37-4 (capreomycin sulfate).
ATC — J04AB30.
ATC Vet — QJ04AB30.

Description.

Capreomycin I consists of capreomycin IA (C 25 H 44 N 14 O 8 = 668.7) and capreomycin IB (C 25 H 44 N 14 O 7 = 652.7), which predominates. Capreomycin II, which makes up about 10% of the mixture, consists of capreomycin IIA and capreomycin IIB.

Pharmacopoeias.

In Chin. and US.

USP 31

(Capreomycin Sulfate). The disulfate of capreomycin, a polypeptide mixture produced by the growth of Streptomyces capreolus. It contains not less than 90% of capreomycin I. A white to practically white amorphous powder. Freely soluble in water; practically insoluble in most organic solvents. pH of a 3% solution in water is between 4.5 and 7.5. Store in airtight containers.

💊 Adverse Effects and Treatment

The effects of capreomycin on the kidney and eighth cranial nerve are similar to those of aminoglycosides such as gentamicin. Nitrogen retention, renal tubular dysfunction, and progressive renal damage may occur. Hypokalaemia and other electrolyte abnormalities have been reported. Vertigo, tinnitus, and hearing loss may also occur and are sometimes irreversible. Abnormalities in liver function have been reported when capreomycin has been used with other antituberculous drugs. Hypersensitivity reactions including urticaria, maculopapular rashes, and sometimes fever have been reported. Leucocytosis and leucopenia have also been observed. Thrombocytopenia has been reported rarely. Eosinophilia commonly occurs with capreomycin. Capreomycin also has a neuromuscular blocking action. There may be pain, induration, and excessive bleeding at the site of intramuscular injection; sterile abscesses may also form. Teratogenicity has been seen after high doses in rodents. Treatment of overdose is generally supportive. Patients with normal renal function should be hydrated to maintain adequate urine output. Capreomycin may be removed by haemodialysis in patients with significant renal impairment.

Impurities.

The manufacturer of a highly-purified capreomycin product (Capacin; Cheiljedang, Kor.) has claimed that such purification reduces the toxicity and alters the pharmacokinetics in animal studies, suggesting that some of the toxicity of capreomycin is due to such impurities.1
1. Lee SH, et al. The impurities of capreomycin make a difference in the safety and pharmacokinetic profiles. Int J Antimicrob Agents 2003; 22: 81–3.

💊 Precautions

Capreomycin should be given with care and in reduced dosage to patients with renal impairment. Care is also essential in patients with signs of eighth cranial nerve damage. It is advisable to monitor renal and auditory function and serum-potassium concentrations in patients before and during therapy. Periodic assessment of hepatic function is also recommended.

💊 Interactions

Care should be taken when capreomycin is used with other drugs that have neuromuscular blocking activity. It should not be given with other drugs that are ototoxic or nephrotoxic.

💊 Antimicrobial Action

Capreomycin has activity against various mycobacteria. Resistance develops readily if capreomycin is used alone. It shows cross-resistance with kanamycin and neomycin.
1. Ho YII, et al. In-vitro activities of aminoglycoside-aminocyclitols against mycobacteria. J Antimicrob Chemother 1997; 40: 27–32
2. Maus CE, et al. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2005; 49: 3192–7.

💊 Pharmacokinetics

Capreomycin is poorly absorbed from the gastrointestinal tract. An intramuscular dose of 1 g has been reported to give a peak serum concentration of about 30 micrograms/mL after 1 or 2 hours. About 50% of a dose is excreted unchanged in the urine by glomerular filtration within 12 hours. Capreomycin is removed by haemodialysis.

💊 Uses and Administration

Capreomycin is a second-line antimycobacterial that may be used in the treatment of tuberculosis as part of a multidrug regimen when resistance to primary drugs has developed. Capreomycin is given as the sulfate by deep intramuscular injection or by intravenous infusion. The usual dose is the equivalent of 1 g of capreomycin base (maximum 20 mg/kg) given daily for 2 to 4 months, then 2 or 3 times weekly for the remainder of therapy. For details of doses in infants, children, and adolescents, see below.

Administration in children.

For the treatment of drug-resistant tuberculosis in infants, children, and adolescents the American Academy of Pediatrics (AAP) suggests an intramuscular dose of capreomycin 15 to 30 mg/kg daily, to a maximum dose of 1 g daily.

Administration in renal impairment.

As with aminoglycosides, the dose of capreomycin in patients with renal impairment must be reduced based on creatinine clearance; the desired steady-state serum capreomycin level is 10 micrograms/mL.

💊 Preparations

USP 31: Capreomycin for Injection.

Proprietary Preparations

Austral.: Capastat; Austria: Capastat; Cz.: Capastat†; Gr.: Capastat; Rus.: Capastat (Капастат); Lykocin (Лайкоцин); Spain: Capastat; UK: Capastat; USA: Capastat.
Published December 08, 2018.