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ALERT: U.S. Boxed Warning

The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.

Pronunciation

(kap ree oh MYE sin)

Generic Available (U.S.)

No

Index Terms

• Capreomycin Sulfate

U.S. Brand Names

• Capastat® Sulfate

Pharmacologic Category

• Antibiotic, Miscellaneous
• Antitubercular Agent

Pharmacologic Category Synonyms

• Tuberculosis Treatment Agent

Use: Labeled Indications

Treatment of tuberculosis in conjunction with at least one other antituberculosis agent

Pregnancy Risk Factor

C

Pregnancy Considerations

Capreomycin has been shown to be teratogenic in animal studies. [U.S. Boxed Warning]: Safety has not been established in pregnant women; use during pregnancy only if the potential benefit to the mother outweighs the possible risk to the fetus.

Lactation

Excretion in breast milk unknown/use caution

Contraindications

Hypersensitivity to capreomycin or any component of the formulation

Warnings/Precautions

Boxed warnings:

• Auditory impairment: See “Disease-related concerns and Concurrent drug therapy issues” below.

• Pediatrics: See “Special populations” below.

• Pregnancy: See “Special populations” below.

• Renal impairment: See “Disease-related concerns and Concurrent drug therapy issues” below.

Concerns related to adverse effects:

• Electrolyte imbalance: Hypocalcemia, hypokalemia, and hypomagnesemia have been reported with use.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Auditory impairment: [U.S. Boxed Warning]: Use in patients with pre-existing auditory impairment must be undertaken with great caution, and the risk of additional eighth nerve impairment should be weighed against the benefits to be derived from therapy.

• Renal impairment: [U.S. Boxed Warning]: Use in patients with renal impairment must be undertaken with great caution, and the risk of additional renal injury should be weighed against the benefits to be derived from therapy. Dosage reductions are recommended for known or suspected renal impairment.

Concurrent drug therapy issues:

• Drugs with ototoxic or nephrotoxic potential: [U.S. Boxed Warning]: Use with nonantituberculous drugs (ie, aminoglycoside antibiotics) having ototoxic or nephrotoxic potential should be undertaken only with great caution.

• Parenteral antituberculous agents: [U.S. Boxed Warning]: Since other parenteral antituberculous agents (eg, streptomycin) also have similar and sometimes irreversible toxic effects, particularly on eighth cranial nerve and renal function, simultaneous administration of these agents with capreomycin is not recommended.

Special populations;

• Elderly: Use with caution in the elderly.

• Pediatrics: [U.S. Boxed Warning]: Safety has not been established in children.

• Pregnancy: [U.S. Boxed Warning]: Safety has not been established in pregnant women.

Adverse Reactions

>10%:

Otic: Ototoxicity (subclinical hearing loss: 11%; clinical loss: 3%)

Renal: Nephrotoxicity (36%, increased BUN)

1% to 10%: Hematologic: Eosinophilia (dose related, mild)

<1%, postmarketing, and/or case reports: Acute tubular necrosis, Bartter's syndrome, creatinine increased, hypersensitivity (maculopapular rash, urticaria and/or fever), hypocalcemia, hypokalemia, hypomagnesemia, injection site reactions (abscess, bleeding, induration and pain), leukocytosis, leukopenia, liver function decreased (BSP excretion decreased), renal injury, thrombocytopenia (rare), tinnitus, toxic nephritis, urinary sediment abnormal, vertigo

Drug Interactions

Aminoglycosides: Capreomycin may enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy

BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Colistimethate: Capreomycin may enhance the neuromuscular-blocking effect of Colistimethate. Risk C: Monitor therapy

Neuromuscular-Blocking Agents: Capreomycin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy

Polymyxin B: Capreomycin may enhance the neuromuscular-blocking effect of Polymyxin B. Risk C: Monitor therapy

Storage

Powder for injection should be stored at room temperature of 15°C to 30°C (59°F to 86°F). Following reconstitution, may store under refrigeration for up to 24 hours.

Reconstitution

Dissolve powder with 2 mL of NS or SWFI; allow 2-3 minutes for dissolution.

For I.V. administration: Further dilute in NS 100 mL.

For I.M. administration:

1 g dose: Administer contents of reconstituted vial

<1 g dose: See table:

Mechanism of Action

Capreomycin is a cyclic polypeptide antimicrobial. It is administered as a mixture of capreomycin IA and capreomycin IB. The mechanism of action of capreomycin is not well understood. Mycobacterial species that have become resistant to other agents are usually still sensitive to the action of capreomycin. However, significant cross-resistance with viomycin, kanamycin, and neomycin occurs.

Pharmacodynamics/Kinetics

Half-life elimination: Normal renal function: 4-6 hours; Cl_cr 100-110 mL/minute: 5-6 hours; Cl_cr 50-80 mL/minute: 7-10 hours; Cl_cr 20-40 mL/minute: 12-20 hours; Cl_cr 10 mL/minute: 29 hours; Cl_cr 0 mL/minute: 55 hours

Time to peak, serum: I.M.: 1-2 hours

Excretion: Urine (52% within 12 hours)

Dosage

I.M., I.V.:

Infants and Children <15 years and ≤40 kg (unlabeled use): 15-30 mg/kg/day (maximum: 1 g/day) for 2-4 months, followed by 15-30 mg/kg (maximum: 1 g/day) twice weekly (MMWR, 2003)

Children ≥15 years or >40 kg (unlabeled use): 15 mg/kg/day (maximum: 1 g/dose) for 2-4 months followed by 15 mg/kg (maximum: 1 g/dose) 2-3 times/week (MMWR, 2003)

Adults: 1 g/day (maximum: 20 mg/kg/day) for 60-120 days, followed by 1 g 2-3 times/week or 15 mg/kg/day (maximum: 1 g/dose) for 2-4 months, followed by 15 mg/kg (maximum: 1 g/dose) 2-3 times/week (MMWR, 2003)

Elderly: Use with caution due to the increased potential for pre-existing renal dysfunction or impaired hearing. The manufacturer recommends initiating at lower end of dosing range. Adults >59 years of age: 10 mg/kg (maximum: 750 mg/dose) for 5-7 days per week for 2-4 months, followed by 10 mg/kg (maximum: 750 mg/dose) 2-3 times/week (MMWR, 2003).

Dosing interval in renal impairment: Adults:

The FDA-approved labeling contains the following renal dosing adjustment guidelines (maximum: 1 g/dose):

Cl_cr 110 mL/minute: Administer 13.9 mg/kg every 24 hours

Cl_cr 100 mL/minute: Administer 12.7 mg/kg every 24 hours

Cl_cr 80 mL/minute: Administer 10.4 mg/kg every 24 hours

Cl_cr 60 mL/minute: Administer 8.2 mg/kg every 24 hours

Cl_cr 50 mL/minute: Administer 7 mg/kg every 24 hours or 14 mg/kg every 48 hours

Cl_cr 40 mL/minute: Administer 5.9 mg/kg every 24 hours or 11.7 mg/kg every 48 hours

Cl_cr 30 mL/minute: Administer 4.7 mg/kg every 24 hours or 9.5 mg/kg every 48 hours or 14.2 mg/kg every 72 hours

Cl_cr 20 mL/minute: Administer 3.6 mg/kg every 24 hours or 7.2 mg/kg every 48 hours or 10.7 mg/kg every 72 hours

Cl_cr 10 mL/minute: Administer 2.4 mg/kg every 24 hours or 4.9 mg/kg every 48 hours or 7.3 mg/kg every 72 hours

Cl_cr 0 mL/minute: Administer 1.3 mg/kg every 24 hours or 2.6 mg/kg every 48 hours or 3.9 mg/kg every 72 hours

The following (unlabeled) guidelines may also be used:

MMWR, 2003:

Cl_cr ≥30 mL/minute: No adjustment required

Cl_cr <30 mL/minute and hemodialysis: 12-15 mg/kg (maximum: 1 g/dose) 2-3 days per week (NOT daily)

Aronoff, 2007:

Cl_cr ≥10 mL/minute: 1 g every 24 hours

Cl_cr <10 mL/minute: 1 g every 48 hours

Hemodialysis: Administer dose after hemodialysis only

Continuous renal replacement therapy (CRRT): 5 mg/kg every 24 hours

Administration: I.M.

Administer by deep I.M. injection into a large muscle mass.

Administration: I.V.

Administer over 60 minutes.

Monitoring Parameters

Audiometric measurements and vestibular function at baseline and during therapy; renal function at baseline and weekly during therapy; frequent assessment of serum electrolytes (including calcium, magnesium, and potassium), liver function tests

Reference Range

Recommended concentration for susceptibility testing: 10 mcg/mL

Geriatric Considerations

Has not been studied in the elderly. I.M. administration may limit use due to painful injection or lack of sites in patients with decreased muscle mass. Use with caution in patients with pre-existing hearing impairment due to potential ototoxicity.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness

Mental Health: Effects on Psychiatric Treatment

None reported

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution, as sulfate:

Capastat® Sulfate: 1 g

References

Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.

Davidson PT and Le HQ, “Drug Treatment of Tuberculosis - 1992,” Drugs, 1992, 43(5):651-73.

“Drugs for Tuberculosis,” Med Lett Drugs Ther, 1993, 35(908):99-101.

Iseman MD, “Treatment of Multidrug-Resistant Tuberculosis,” N Engl J Med, 1993, 329(11):784-91.

Lehmann CR, Garrett LE, Winn RE, et al, “Capreomycin Kinetics in Renal Impairment and Clearance by Hemodialysis,” Am Rev Respir Dis, 1988, 138(5):1312-3.

“Treatment of Tuberculosis. Joint Statement of the American Thoracic Society, CDC, and the Infectious Diseases Society of America.” Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm

International Brand Names

• Capacin (KP)
• Capastat (AT, AU, CZ, ES, GB, GR, IE, PL, RU)
• Kapocin (IN)

Lexi-Comp.com

Last full review/revision March 2011