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.
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.
The safety of the use capreomycin in pregnancy has not been determined.
Safety and effectiveness in pediatric patients have not been established.
Tuberculosis, pulmonary (alternative agent): Note: Current guidelines recommend against the use of capreomycin (ATS/CDC/ERS/IDSA [Nahid 2019]).
IM, IV: 15 mg/kg once daily or 25 mg/kg 3 times weekly, in combination with other appropriate agents; duration depends on clinical and microbiological response (ATS/CDC/IDSA [Nahid 2016]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Adults:
Manufacturer's 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:
CrCl ≥30 mL/minute: No adjustment necessary (ATS/CDC/IDSA [Nahid 2016]).
CrCl <30 mL/minute: 15 mg/kg/dose 2 to 3 times weekly (ATS/CDC/IDSA [Nahid 2016]).
End-stage renal disease on hemodialysis: 15 mg/kg/dose 2 to 3 times weekly; administer after hemodialysis if given on dialysis days (ATS/CDC/IDSA [Nahid 2016]).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Capreomycin: Pediatric drug information")
Active tuberculosis infection; treatment multidrug resistant (MDR) (second-line therapy): Limited data available: Note: Always use as part of a multidrug regimen. Any regimens using less than once daily dosing should administer dosing as directly observed therapy (DOT). Treatment regimens for MDR TB are variable depending upon sensitivity and clinical response. Capreomycin frequency and dosing differs depending on treatment regimen selected; consult current drug-sensitive TB guidelines for detailed information (ATS/CDC/IDSA [Nahid 2016]; Schaaf 2015).
Primary pulmonary disease:
Once-daily therapy:
Infants, Children, and Adolescents <15 years, weighing ≤40 kg: Note: Suggested expert dosing range is large and variable (Schaaf 2015): IM, IV: 15 to 30 mg/kg/dose once daily; some experts recommend an initial dose range of 15 to 20 mg/kg/dose once daily; maximum daily dose: 1,000 mg/day; monitor serum concentrations (ATS/CDC/IDSA [Nahid 2016]; DHHS [pediatric] 2013; Schaaf 2015; Seddon 2012).
Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: IM, IV: 15 mg/kg/dose once daily; maximum daily dose: 1,000 mg/day; monitor serum concentrations (ATS/CDC/IDSA [Nahid 2016]; HHS [adult] 2016; Seddon 2012).
Three-times-weekly DOT: Children and Adolescents <15 years weighing >40 kg or Adolescents ≥15 years: IM, IV: 25 mg/kg/dose three times weekly; maximum dose: 1,000 mg/dose (ATS/CDC/IDSA [Nahid 2016].
Twice-weekly DOT: Infants, Children, and Adolescents <15 years, weighing ≤40 kg: IM, IV: 25 to 30 mg/kg/dose twice weekly; maximum dose: 1,000 mg/dose (ATS/CDC/IDSA [Nahid 2016]).
Meningitis (independent of HIV-status): Infants, Children, and Adolescents: Suggested expert dosing range is large and variable (Schaaf 2015): IM, IV: 15 to 30 mg/kg/dose once daily; some experts recommend an initial range of 15 to 20 mg/kg/dose once daily; maximum daily dose: 1,000 mg/day; monitor serum concentrations (ATS/CDC/IDSA [Nahid 2016]; DHHS [pediatric] 2013; Red Book [AAP 2015]; Schaaf 2015).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Drug clearance is decreased and half-life increased with decreasing renal function; specific recommendations in pediatric patients are lacking; consider dosing adjustment and frequent therapeutic drug monitoring in patients with renal impairment (ATS/CDC/IDSA [Nahid 2016]).
There are no dosage adjustments provided in the manufacturer's labeling; some suggest that no extra precautions are needed (CDC 2003).
Use with caution because of the increased potential for preexisting renal dysfunction or impaired hearing. For older patients, consider giving 15 mg/kg 3 times weekly to allow for drug clearance (ATS/CDC/IDSA [Nahid 2016]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Injection, as sulfate [preservative free]:
Capastat Sulfate: 1 g (1 ea [DSC])
No
IM: Administer by deep IM injection into a large muscle mass.
IV: Administer over 60 minutes.
Parenteral:
IV: Administer over 60 minutes.
IM: Administer by deep IM injection into large muscle mass
Tuberculosis, pulmonary: Alternative agent for the treatment of pulmonary infections caused by capreomycin-susceptible strains of Mycobacterium tuberculosis, in combination with other appropriate antituberculosis agents, when other agents have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli (ATS/CDC/IDSA [Nahid 2016]).
Capastat may be confused with Cepastat
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
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%, postmarketing, and/or case reports: 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), leukocytosis, leukopenia, nephritis (toxic), renal tubular necrosis, thrombocytopenia (rare), tinnitus, urine sedimentation abnormality, vertigo
Hypersensitivity to capreomycin or any component of the formulation
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:
• 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:
• Older adult: 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.
May cause renal injury including tubular necrosis, elevated BUN or serum creatinine, and abnormal urinary sediment; BUN elevation and abnormal urinary sediment are associated with prolonged therapy and the clinical significance of these findings is not fully established. Proteinuria frequently reported; electrolyte disturbances (hypokalemia, hypomagnesemia, and hypocalcemia) may result from renal injury (CDC, 2003). Discontinuation of therapy due to renal toxicity has been reported in 20% to 25% of patients (CDC, 2003). Monitor renal function; urinalysis and electrolytes at baseline and periodically (monthly) throughout therapy (CDC, 2003; Seddon, 2012). May cause hearing loss; some cases may be irreversible. Tinnitus and vertigo have also been reported; more common in elderly patients and patients with preexisting renal impairment. In pediatric patients treated for multidrug-resistant TB, the reported incidence of hearing loss is variable (7% to 24%) with regimens that included either capreomycin or an aminoglycoside; the majority of children received amikacin compared to capreomycin; specific incidence with capreomycin not determined (Drobac, 2006; Seddon, 2013).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: Capreomycin may enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Colistimethate: Capreomycin may enhance the neuromuscular-blocking effect of Colistimethate. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mecamylamine: Capreomycin may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
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
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. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Evaluate pregnancy status prior to treatment of multidrug-resistant tuberculosis in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment for multidrug-resistant tuberculosis (Esmail 2018).
[US Boxed Warning]: The safety of the use of capreomycin in pregnancy has not been determined.
Active tuberculosis infection is associated with adverse fetal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020), as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020).
Data are limited for use of second-line drugs during pregnancy (ie, capreomycin). The treatment of multidrug-resistant tuberculosis in pregnant patients should be individualized; evidence to support a specific regimen is not available; however, agents other than capreomycin are preferred if an injectable agent is needed (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020).
It is not known if capreomycin is present in breast milk.
Capreomycin is not significantly absorbed when administered orally, limiting any potential exposure via breast milk. The manufacturer recommends that caution be exercised when administering capreomycin to breastfeeding women. Patients with multidrug-resistant tuberculosis and a sputum smear-positive test should avoid breastfeeding when possible (Esmail 2018).
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
Recommended concentration for susceptibility testing: 10 mcg/mL (ATS/CDC/IDSA 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.
Absorption: Oral: Not absorbed
Half-life elimination: 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
Time to peak, serum: IM: 1 to 2 hours
Excretion: Urine (52% unchanged within 12 hours)
Solution (reconstituted) (Capastat Sulfate Injection)
1 g (per each): $258.54
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