(kap ree oh MYE sin)
Tuberculosis, pulmonary: Treatment of pulmonary infections caused by capreomycin-susceptible strains of Mycobacterium tuberculosis, in combination with other appropriate antituberculosis agents, when the primary agents (eg, isoniazid, rifampin, ethambutol, pyrazinamide) have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli.
Hypersensitivity to capreomycin or any component of the formulation
The use of capreomycin in patients with renal insufficiency must be undertaken with great caution, and the risk of additional renal injury should be weighed against the benefits derived from therapy.
Because other parenteral antituberculosis agents (streptomycin, viomycin) also have similar and sometimes irreversible toxic effects, particularly on renal function, simultaneous administration of these agents with capreomycin is not recommended. Use with nonantituberculosis drugs (polymyxin A sulfate, colistin sulfate, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, and neomycin) having nephrotoxic potential should be undertaken only with great caution.
Auditory impairment:The use of capreomycin in patients with preexisting auditory impairment must be undertaken with great caution, and the risk of additional cranial nerve VIII impairment should be weighed against the benefits derived from therapy.
Because other parenteral antituberculosis agents (streptomycin, viomycin) also have similar and sometimes irreversible toxic effects, particularly on cranial nerve VIII, simultaneous administration of these agents with capreomycin is not recommended. Use with nonantituberculosis drugs (polymyxin A sulfate, colistin sulfate, amikacin, gentamicin, tobramycin, vancomycin, kanamycin, and neomycin) having ototoxic potential should be undertaken only with great caution.
Pregnancy:The safety of the use capreomycin in pregnancy has not been determined.
Pediatric patients:Safety and effectiveness in pediatric patients have not been established.
Tuberculosis, pulmonary: IM, IV:
Manufacturers labeling: 1 g once daily (maximum: 20 mg/kg/dose) for 60 to 120 days, followed by 1 g 2 to 3 times weekly
Alternate dosing: 15 mg/kg once daily (maximum: 1 g/dose) for 5 to 7 days per week for 2 to 4 months, followed by 15 mg/kg (maximum: 1 g/dose) 2 to 3 times weekly (MMWR 2003)
Use with caution because of the increased potential for preexisting renal dysfunction or impaired hearing.
Manufacturers labeling: Refer to adult dosing. Initiate at lower end of dosing range.
Alternate dosing: Adults >59 years of age: 10 mg/kg once daily (maximum: 750 mg/dose) for 5 to 7 days per week for 2 to 4 months, followed by 10 mg/kg (maximum: 750 mg/dose) 2 to 3 times weekly (MMWR 2003).
Tuberculosis, pulmonary:
Infants, Children, and Adolescents <15 years and ≤40 kg (off-label use): IM, IV: 15 to 30 mg/kg/dose (maximum: 1,000 mg/dose) once daily or twice weekly (MMWR 2003)
Children and Adolescents ≥15 years or >40 kg (off-label use): IM, IV: 15 mg/kg once daily (maximum: 1,000 mg/dose) for 5 to 7 days per week for 2 to 4 months followed by 15 mg/kg (maximum: 1,000 mg/dose) 2 to 3 times weekly (MMWR 2003)
Adults:
Manufacturers labeling (maximum: 1 g/dose):
CrCl 110 mL/minute: 13.9 mg/kg every 24 hours
CrCl 100 mL/minute: 12.7 mg/kg every 24 hours
CrCl 80 mL/minute: 10.4 mg/kg every 24 hours
CrCl 60 mL/minute: 8.2 mg/kg every 24 hours
CrCl 50 mL/minute: 7 mg/kg every 24 hours or 14 mg/kg every 48 hours
CrCl 40 mL/minute: 5.9 mg/kg every 24 hours or 11.7 mg/kg every 48 hours
CrCl 30 mL/minute: 4.7 mg/kg every 24 hours or 9.5 mg/kg every 48 hours or 14.2 mg/kg every 72 hours
CrCl 20 mL/minute: 3.6 mg/kg every 24 hours or 7.2 mg/kg every 48 hours or 10.7 mg/kg every 72 hours
CrCl 10 mL/minute: 2.4 mg/kg every 24 hours or 4.9 mg/kg every 48 hours or 7.3 mg/kg every 72 hours
CrCl 0 mL/minute: 1.3 mg/kg every 24 hours or 2.6 mg/kg every 48 hours or 3.9 mg/kg every 72 hours
Alternate dosing:
MMWR 2003:
CrCl ≥30 mL/minute: No adjustment necessary.
CrCl <30 mL/minute: 12 to 15 mg/kg (maximum: 1 g/dose) 2 to 3 days per week (NOT daily)
End-stage renal disease (ESRD) on hemodialysis: 12 to 15 mg/kg (maximum: 1 g/dose) 2 to 3 days per week (NOT daily)
Aronoff 2007:
GFR ≥10 mL/minute: 1 g every 24 hours
GFR <10 mL/minute: 1 g every 48 hours
End-stage renal disease (ESRD) on hemodialysis: Administer dose after hemodialysis only
Continuous renal replacement therapy (CRRT): 5 mg/kg every 24 hours
There are no dosage adjustments provided in the manufacturer 's labeling.
Reconstitute with 2 mL of NS or SWFI; allow 2 to 3 minutes for dissolution.
For IV administration: Further dilute in NS 100 mL.
For IM administration:
1 g dose: Administer contents of reconstituted vial
<1 g dose: See table:
Capreomycin Dilution for Doses <1 g (IM Administration)Diluent Volume
(mL)
Capreomycin Solution Volume
(mL)
Final Concentration
(approximate)
2.15
2.85
370 mg/mL
2.63
3.33
315 mg/mL
3.3
4
260 mg/mL
4.3
5
210 mg/mL
Table has been converted to the following text.
Capreomycin Dilution for Doses <1 g (IM Administration):
Diluent volume 2.15 mL and capreomycin solution volume 2.85 mL for a final concentration of ~370 mg/mL
Diluent volume 2.63 mL and capreomycin solution volume 3.33 mL for a final concentration of ~315 mg/mL
Diluent volume 3.3 mL and capreomycin solution volume 4 mL for a final concentration of ~260 mg/mL
Diluent volume 4.3 mL and capreomycin solution volume 5 mL for a final concentration of ~210 mg/mL
IM: Administer by deep IM injection into a large muscle mass.
IV: Administer over 60 minutes.
Store intact vials at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Following reconstitution, may store under refrigeration for up to 24 hours.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection, as sulfate:
Capastat Sulfate: 1 g (1 ea)
Aminoglycosides: Capreomycin may enhance the neuromuscular-blocking effect of Aminoglycosides. Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination
Colistimethate: Capreomycin may enhance the neuromuscular-blocking effect of Colistimethate. Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Mecamylamine: Capreomycin may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination
Neuromuscular-Blocking Agents: Capreomycin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Polymyxin B: Capreomycin may enhance the neuromuscular-blocking effect of Polymyxin B. Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Audiometric measurements and vestibular function at baseline and during therapy; renal function at baseline and weekly during therapy; baseline and frequent assessment of serum electrolytes (including calcium, magnesium, and potassium), liver function tests
Frequency not always defined.
>10%:
Otic: Ototoxicity (subclinical hearing loss: 11%; clinical loss: 3%)
Genitourinary: Nephrotoxicity (36%, increased blood urea nitrogen)
1% to 10%: Hematologic: Eosinophilia (dose-related, mild)
<1% (Limited to important or life-threatening): Bartters syndrome, hepatic insufficiency (decreased sulfobromophthalein excretion), hypersensitivity (includes fever, maculopapular rash, urticaria), hypocalcemia, hypokalemia, hypomagnesemia, increased serum creatinine, injection site reaction (includes abscess at injection site, bleeding at injection site, induration at injection site, and pain at injection site), kidney damage, leukocytosis, leukopenia, nephritis (toxic), renal tubular necrosis, thrombocytopenia (rare), tinnitus, urine sedimentation abnormality, vertigo
Concerns related to adverse effects:
- Electrolyte imbalance: Hypocalcemia, hypokalemia, and hypomagnesemia have been reported with use. Monitor electrolytes periodically during treatment.
- Nephrotoxicity: May cause nephrotoxicity, including tubular necrosis, increased BUN or serum creatinine, and abnormal urinary sediment; slight elevations in BUN and serum creatinine with urinary RBCs, WBCs, and casts have been observed with prolonged treatment. Monitor renal function at baseline and periodically during treatment. A BUN >30 mg/dL or other evidence of decreasing renal function should prompt clinical evaluation and dosage adjustment or therapy discontinuation.
- Ototoxicity: May cause impairment of cranial nerve VIII, which may be irreversible; perform audiometric assessment and assessment of vestibular function prior to initiation and periodically during treatment.
- 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:
- Allergies: Use with caution in patients who demonstrate some form of allergy.
- Auditory impairment: [US Boxed Warning]: Use in patients with preexisting auditory impairment must be undertaken with great caution, and the risk of additional cranial nerve VIII impairment should be weighed against the benefits to be derived from therapy.
- Renal impairment: [US 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:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Drugs with ototoxic or nephrotoxic potential: [US Boxed Warning]: Use with nonantituberculous drugs (eg, polymyxin A sulfate, colistin sulfate, gentamicin, tobramycin, vancomycin, neomycin) having ototoxic or nephrotoxic potential should be undertaken only with great caution.
- Parenteral antituberculous agents: [US Boxed Warning]: Because other parenteral antituberculous agents (eg, streptomycin, viomycin) also have similar and sometimes irreversible toxic effects, particularly on cranial nerve VIII and renal function, simultaneous administration of these agents with capreomycin is not recommended.
Special populations:
- Elderly: Use with caution.
- Pediatric: [US Boxed Warning]: Safety has not been established in pediatric patients.
- Pregnancy: [US Boxed Warning]: Safety has not been established in pregnant women.
C
Adverse events have been reported in animal reproduction studies. [US Boxed Warning]: Safety has not been established in pregnant women; avoid use during pregnancy because of the risk of fetal nephrotoxicity and congenital hearing loss (MMWR 2003).
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.
Oral: Not absorbed
Urine (52% unchanged within 12 hours)
Serum: IM: 1 to 2 hours
CrCl 100 to 110 mL/minute: 5 to 6 hours; CrCl 50 to 80 mL/minute: 7 to 10 hours; CrCl 20 to 40 mL/minute: 12 to 20 hours; CrCl 10 mL/minute: 29 hours; CrCl 0 mL/minute: 55 hours
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, nausea, or vomiting), change in balance, hearing impairment, urinary retention, change in amount of urine passed, tinnitus, or injection site pain or irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.