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    Antibiotics for Tuberculosis

    BOXED WARNING

    Dehydration, nephrotoxicity, renal impairment

    Use capreomycin with caution in patients with renal insufficiency, and weigh the risk of additional renal injury against the benefits to be derived from therapy. The risk of toxic reactions to capreomycin may be greater in patients with renal impairment. Patients with abnormal renal function or dehydration and patients receiving other nephrotoxic drugs are at much greater risk for developing acute tubular necrosis. Damage to the auditory and vestibular divisions of cranial nerve VIII has been associated with capreomycin given to patients with abnormal renal function or dehydration. Monitor renal function before starting capreomycin therapy and weekly during treatment. Reduce the capreomycin dosage in patients with known or suspected renal impairment. Simultaneous use of other parenteral antituberculosis agents with similar and irreversible nephrotoxicity is not recommended; use nonantituberculosis drugs with nephrotoxic potential concomitantly only with caution.[44155]

    Hearing impairment, ototoxicity

    Use capreomycin with caution in patients with preexisting hearing impairment, and weigh the risk of additional cranial nerve VIII impairment against the benefits to be derived from therapy. Damage to the auditory and vestibular divisions of cranial nerve VIII has been associated with capreomycin given to patients with abnormal renal function or dehydration and in those receiving medications with additive auditory toxicities. Perform audiometric measurements and assessment of vestibular function before starting capreomycin and at regular intervals during treatment. Simultaneous use of other parenteral antituberculosis agents with similar and irreversible ototoxicity is not recommended; use nonantituberculosis drugs with ototoxic potential concomitantly only with caution.[44155]

    Children, infants, neonates

    Safety and effectiveness have not been established in neonates, infants, or children. Although capreomycin is not FDA-approved for pediatric use, tuberculosis guidelines include pediatric dosing recommendations.[44155] [61094]

    Pregnancy

    The safety of the use of capreomycin in pregnancy has not been established. Use capreomycin during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. Capreomycin has been shown to be teratogenic in rats when given in doses 3.5 times the human dose. In teratology studies, a low incidence of "wavy ribs" was noted in litters of female rats treated with daily doses of capreomycin 50 mg/kg or more.[44155]

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral polypeptide antibiotic, exact mechanism unknown.
    Used as a second line agent in combination with other medications for the treatment of pulmonary tuberculosis.
    Practical use is limited by routes of administration, adverse effects of nephrotoxicity and neurotoxicity.

    COMMON BRAND NAMES

    Capastat

    HOW SUPPLIED

    Capastat Intramuscular Inj Pwd F/Sol: 1g
    Capastat Intravenous Inj Pwd F/Sol: 1g

    DOSAGE & INDICATIONS

    For the treatment of drug-susceptible tuberculosis infection as part of combination therapy.
    NOTE: Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for dosing in patients with marked obesity.
    For the treatment of drug-susceptible tuberculosis infection in persons without HIV as part of combination therapy.
    Intravenous or Intramuscular dosage
    Adults

    15 mg/kg/dose IV or IM once daily or 5 days/week, or alternatively, 25 mg/kg/dose IV or IM 3 days/week.[44155] [61094] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Use adjusted body weight in obese patients.[65645] The FDA-approved dosage is 1 g IV or IM once daily (Max: 20 mg/kg/day) for 60 to 120 days, followed by 1 g IV or IM 3 days/week or twice weekly for a total treatment period of 12 to 24 months.[44155] Capreomycin is generally recommended as second-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Infants†, Children†, and Adolescents†

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively 25 to 30 mg/kg/dose IV or IM twice weekly.[61094] Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients.[65645] Capreomycin is generally recommended as second-line therapy; duration is dependent on the site of involvement.

    Neonates†

    15 to 30 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Capreomycin is generally recommended as second line therapy; duration is dependent on the site of involvement.

    For the treatment of drug-susceptible tuberculosis infection in persons living with HIV as part of combination therapy.
    Intravenous or Intramuscular dosage
    Adults

    15 mg/kg/dose IV or IM once daily or 5 days/week.[34362] [61094] Daily dosing is defined as 5- or 7 days/week.[61094] Use adjusted body weight in obese patients.[65645] The FDA-approved dosage is 1 g IV or IM once daily (Max: 20 mg/kg/day) for 60 to 120 days, followed by 1 g IV or IM 3 days/week or twice weekly for a total treatment period of 12 to 24 months.[44155] Capreomycin is generally recommended as second-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Infants†, Children†, and Adolescents†

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week.[34361] [34362] [61094] Daily dosing is defined as 5- or 7 days/week.[61094] Use adjusted body weight in obese patients.[65645] Capreomycin is generally recommended as second-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Neonates†

    15 to 30 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Capreomycin is generally recommended as second line therapy; duration is dependent on the site of involvement.[53484]

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy.
    NOTE: Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for dosing in patients with marked obesity.
    For the treatment of drug-resistant tuberculosis infection as part of combination therapy in persons without HIV.
    Intravenous or Intramuscular dosage
    Adults

    15 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 mg/kg/dose IV or IM 3 days/week. Daily dosing is preferred and is defined as 5- or 7 days/week. The FDA-approved dosage is 1 g IV or IM once daily (Max: 20 mg/kg/day) for 60 to 120 days, followed by 1 g IV or IM 3 days/week or twice weekly for a total treatment period of 12 to 24 months. Some guidelines no longer recommend use.

    Infants†, Children†, and Adolescents†

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week. Daily dosing is defined as 5- or 7 days/week. Some guidelines no longer recommend use.

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy in persons living with HIV.
    Intravenous or Intramuscular dosage
    Adults

    15 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week. Daily dosing is defined as 5- or 7 days/week. The FDA-approved dosage is 1 g IV or IM once daily (Max: 20 mg/kg/day) for 60 to 120 days, followed by 1 g IV or IM 3 days/week or twice weekly for a total treatment period of 12 to 24 months. Some guidelines no longer recommend use.

    Infants†, Children†, and Adolescents†

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week. Daily dosing is defined as 5- or 7 days/week. Some guidelines no longer recommend use.

    MAXIMUM DOSAGE

    Adults

    1 g/day (20 mg/kg/day) or 5 days/week IV/IM or 25 mg/kg/dose IV/IM 3 days/week.

    Geriatric

    1 g/day (20 mg/kg/day) or 5 days/week IV/IM or 25 mg/kg/dose IV/IM 3 days/week.

    Adolescents

    Safety and efficacy have not been established; however, 30 mg/kg/day (Max: 1 g/day), 5 days/week, or twice weekly IV/IM has been used off-label.

    Children

    Safety and efficacy have not been established; however, 30 mg/kg/day (Max: 1 g/day), 5 days/week, or twice weekly IV/IM has been used off-label.

    Infants

    Safety and efficacy have not been established; however, 30 mg/kg/day, 5 days/week, or twice weekly IV/IM has been used off-label.

    Neonates

    Safety and efficacy have not been established; however, 30 mg/kg/day IV/IM has been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Adult patients (FDA-approved labeling) [44155]
    NOTE: Dosages designed to achieve mean steady-state capreomycin concentration of 10 mcg/mL.
    CrCl 80 mL/minute or more: No dosage adjustment needed.
    CrCl 60 to 79 mL/minute: 8.16 mg/kg IV or IM every 24 hours.
    CrCl 50 to 59 mL/minute: 7.01 mg/kg IV or IM every 24 hours or 14 mg/kg IV or IM every 48 hours.
    CrCl 40 to 49 mL/minute: 5.87 mg/kg IV or IM every 24 hours or 11.7 mg/kg IV or IM every 48 hours.
    CrCl 30 to 39 mL/minute: 4.72 mg/kg IV or IM every 24 hours, 9.45 mg/kg IV or IM every 48 hours, or 14.2 mg/kg IV or IM every 72 hours.
    CrCl 20 to 29 mL/minute: 3.58 mg/kg IV or IM every 24 hours, 7.16 mg/kg IV or IM every 48 hours, or 10.7 mg/kg IV or IM every 72 hours.
    CrCl 10 to 19 mL/minute: 2.43 mg/kg IV or IM every 24 hours, 4.87 mg/kg IV or IM every 48 hours, or 7.3 mg/kg IV or IM every 72 hours.
    CrCl less than 10 mL/minute: 1.29 mg/kg IV or IM every 24 hours, 2.58 mg/kg IV or IM every 48 hours, or 3.87 mg/kg IV or IM every 72 hours.
     
    Adult patients (guidelines)† [61094] [65645]
    May adjust dosage based on serum concentrations with a target peak of 35 to 45 mcg/mL and trough less than 4 mcg/mL.[34362]
    CrCl 30 mL/minute or more: No dose adjustment needed.
    CrCl less than 30 mL/min: 12 to 15 mg/kg IV or IM administered 3 days/week or twice weekly.
     
    Adult patients (alternative)† [32569]
    CrCl 10 mL/minute or more: No dosage adjustment needed.
    CrCl less than 10 mL/minute: Extend the interval to every 48 hours.
     
    Intermittent hemodialysis
    12 to 15 mg/kg IV or IM administered 3 days/week or twice weekly.[61094] [65645] May adjust dosage based on serum concentrations with a target peak of 35 to 45 mcg/mL and trough less than 4 mcg/mL.[34362] Administer dose after hemodialysis on the day of dialysis.[44159]
     
    Peritoneal dialysis†
    No dosage adjustment needed.[32569]
     
    Continuous renal replacement therapy (CRRT)†
    NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303]
     
    Adult patients
    5 mg/kg/dose IV or IM every 24 hours.[32569]

    ADMINISTRATION

    Injectable Administration

    Capreomycin is administered intravenously or intramuscularly.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Over time, the solution may darken and develop a pale straw color, but this is not associated with loss of potency or the development of toxicity.

    Intravenous Administration

    eReconstitution:
    Reconstitute 1 g with 2 mL of 0.9% Sodium Chloride for injection or Sterile Water for injection and shake well. Allow 2 to 3 minutes for complete dissolution.
    For doses < 1 g, alternate dilutions may be used depending on the desired dose:
    2.15 mL diluent added to 1 g (10 mL) vial provides 2.85 ml capreomycin solution (concentration 370 mg/mL)
    2.63 mL diluent added to 1 g (10 mL) vial provides 3.33 ml capreomycin solution (concentration 315 mg/mL)
    3.3 mL diluent added to 1 g (10 mL) vial provides 4 ml capreomycin solution (concentration 260 mg/mL)
    4.3 mL diluent added to 1 g (10 mL) vial provides 5 ml capreomycin solution (concentration 210 mg/mL)
    Further dilute the desired dosage with 100 mL of 0.9% Sodium Chloride for injection.
    After reconstitution, all solutions of capreomycin may be stored for up to 24 hours under refrigeration.
     
    Intravenous Administration:
    Infuse intravenously over 60 minutes.

    Intramuscular Administration

    Reconstitution:
    Reconstitute 1 g with 2 mL of 0.9% Sodium Chloride for injection or Sterile Water for injection and shake well. Allow 2 to 3 minutes for complete dissolution.
    2.15 mL diluent added to 1 g (10 mL) vial provides 2.85 mL capreomycin solution (concentration 370 mg/mL)
    2.63 mL diluent added to 1 g (10 mL) vial provides 3.33 mL capreomycin solution (concentration 315 mg/mL)
    3.3 mL diluent added to 1 g (10 mL) vial provides 4 mL capreomycin solution(concentration 260 mg/mL)
    4.3 mL diluent added to 1 g (10 mL) vial provides 5 mL capreomycin solution (concentration 210 mg/mL)
    After reconstitution, any solution of capreomycin may be stored for up to 24 hours under refrigeration.
     
    Intramuscular Administration:
    Inject deeply into a large muscle mass.
    Avoid superficial intramuscular injection as it may be associated with increased pain and the development of sterile abscesses.

    STORAGE

    Capastat:
    - Store reconstituted product upright in the refrigerator for use within 24 hours
    - Store unreconstituted product at 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Capreomycin is contraindicated in patients with capreomycin hypersensitivity. Use caution in the administration of capreomycin to any patient who has demonstrated some form of allergy, particularly to drugs.[44155]
     
    A partial neuromuscular blockade was demonstrated after large intravenous doses of capreomycin. This action was enhanced by ether anesthesia and was antagonized by neostigmine.[44155]

    Dehydration, nephrotoxicity, renal impairment

    Use capreomycin with caution in patients with renal insufficiency, and weigh the risk of additional renal injury against the benefits to be derived from therapy. The risk of toxic reactions to capreomycin may be greater in patients with renal impairment. Patients with abnormal renal function or dehydration and patients receiving other nephrotoxic drugs are at much greater risk for developing acute tubular necrosis. Damage to the auditory and vestibular divisions of cranial nerve VIII has been associated with capreomycin given to patients with abnormal renal function or dehydration. Monitor renal function before starting capreomycin therapy and weekly during treatment. Reduce the capreomycin dosage in patients with known or suspected renal impairment. Simultaneous use of other parenteral antituberculosis agents with similar and irreversible nephrotoxicity is not recommended; use nonantituberculosis drugs with nephrotoxic potential concomitantly only with caution.[44155]

    Hearing impairment, ototoxicity

    Use capreomycin with caution in patients with preexisting hearing impairment, and weigh the risk of additional cranial nerve VIII impairment against the benefits to be derived from therapy. Damage to the auditory and vestibular divisions of cranial nerve VIII has been associated with capreomycin given to patients with abnormal renal function or dehydration and in those receiving medications with additive auditory toxicities. Perform audiometric measurements and assessment of vestibular function before starting capreomycin and at regular intervals during treatment. Simultaneous use of other parenteral antituberculosis agents with similar and irreversible ototoxicity is not recommended; use nonantituberculosis drugs with ototoxic potential concomitantly only with caution.[44155]

    Hepatic disease

    Serial tests of liver function have demonstrated a decrease in bromsulphthalein (BSP) excretion without change in AST or ALT in capreomycin-treated patients with preexisting hepatic disease. Abnormal results in liver function tests have occurred in many persons receiving capreomycin in combination with other antituberculosis agents that also are known to cause changes in hepatic function. The role of capreomycin in producing these abnormalities is not clear; however, periodic determinations of liver function are recommended.[44155] Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.[61094]

    Obesity

    Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for capreomycin dosing in patients with marked obesity due to decreased distribution of extracellular fluids in adipose tissues. Follow capreomycin serum concentrations closely when possible. Dosing based on actual body weight will result in supratherapeutic concentrations.[65645]

    Geriatric

    In general, use cautious dose selection for a geriatric patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy. It may be useful to monitor renal function. The geriatric population is also more likely to have impaired hearing at baseline. Perform audiometric measurements and assessment of vestibular function before starting capreomycin and at regular intervals during treatment.[44155] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.[60742] 

    Children, infants, neonates

    Safety and effectiveness have not been established in neonates, infants, or children. Although capreomycin is not FDA-approved for pediatric use, tuberculosis guidelines include pediatric dosing recommendations.[44155] [61094]

    Pregnancy

    The safety of the use of capreomycin in pregnancy has not been established. Use capreomycin during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. Capreomycin has been shown to be teratogenic in rats when given in doses 3.5 times the human dose. In teratology studies, a low incidence of "wavy ribs" was noted in litters of female rats treated with daily doses of capreomycin 50 mg/kg or more.[44155]

    Breast-feeding

    It is unknown whether capreomycin is excreted in human milk. Use caution when capreomycin is administered to a breast-feeding woman. If capreomycin is ingested, toxicity would be unlikely because it is poorly absorbed (less than 1%) from an intact gastrointestinal system.[44155] Capreomycin use as part of multidrug regimens to treat 2 pregnant women with multidrug-resistant tuberculosis, 1 throughout pregnancy and postpartum and the other postpartum only, has been reported. The infants were breast-fed and developing normally except for a mild speech delay in 1 infant and hyperactivity in the other.[48384]

    ADVERSE REACTIONS

    Severe

    azotemia / Delayed / 36.0-36.0
    hearing loss / Delayed / 11.0-11.0
    renal tubular necrosis / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    nephrotoxicity / Delayed / Incidence not known
    ototoxicity / Delayed / Incidence not known

    Moderate

    hypomagnesemia / Delayed / 1.0-10.0
    leukopenia / Delayed / 0-5.0
    hypocalcemia / Delayed / 0-1.0
    thrombocytopenia / Delayed / 0-1.0
    bleeding / Early / 0-1.0
    hypokalemia / Delayed / 10.0
    eosinophilia / Delayed / 5.0
    jaundice / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known

    Mild

    tinnitus / Delayed / 1.0-10.0
    vertigo / Early / 1.0-10.0
    leukocytosis / Delayed / 0-5.0
    urticaria / Rapid / 0-1.0
    fever / Early / 0-1.0
    maculopapular rash / Early / 0-1.0
    injection site reaction / Rapid / 10.0

    DRUG INTERACTIONS

    AbobotulinumtoxinA: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin.
    Acyclovir: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including acyclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Aminoglycosides: (Major) The concomitant use of capreomycin and aminoglycosides may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration of capreomycin with other potentially nephrotoxic drugs, including aminoglycosides may increase serum concentrations of either capreomycin or aminoglycosides. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Aminoglycosides have also been reported to interfere with nerve transmission at the neuromuscular junction. Concomitant administration of capreomycin with aminoglycosides should be avoided if possible; however, if they must be coadministered, use extreme caution.
    Amlodipine; Celecoxib: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Amphotericin B lipid complex (ABLC): (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Amphotericin B liposomal (LAmB): (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Amphotericin B: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including amphotericin B, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Urinary concentrations of capreomycin could interfere with the therapeutic effectiveness of BCG. Postpone instillation of BCG if the patient is receiving antibiotics.
    Bacitracin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including bacitracin, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Botulinum Toxins: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin.
    Bumetanide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to capreomycin may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. Ototoxicity from furosemide or other loop diuretics, while uncommon, can be a transient or permanent side effect of significance. Ototoxicity is best documented with the loop diuretics ethacrynic acid and furosemide, but may also occur with either bumetanide or torsemide. The exact mechanism by which furosemide or other loop diuretics produce ototoxicity is unknown. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended dosages or infusion rates, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If loop diuretics and capreomycin are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Bupivacaine; Lidocaine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lidocaine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Bupivacaine; Meloxicam: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Carboplatin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including carboplatin, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Celecoxib: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Celecoxib; Tramadol: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Cidofovir: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cidofovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Cisplatin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and capreomycin is necessary. Both cisplatin and capreomycin can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
    Clindamycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Clindamycin could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Colistin: (Major) Avoid concomitant administration of capreomycin with colistimethate sodium if possible; however, if they must be coadministered, use extreme caution. Concurrent use of capreomycin and colistimethate sodium may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs like colistimethate sodium may increase serum concentrations of either capreomycin or colistimethate sodium. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Colistimethate sodium has also been reported to interfere with nerve impulse transmission at the neuromuscular junction.
    Cyclosporine: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cyclosporine, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Dextromethorphan; Quinidine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Quinidine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Diclofenac: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Diclofenac; Misoprostol: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Diflunisal: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Diphenhydramine; Ibuprofen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Diphenhydramine; Naproxen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Enflurane: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Entecavir: (Major) Because entecavir is primarily eliminated by the kidneys and capreomycin could affect renal function, concurrent administration may increase entecavir serum concentrations and the risk of adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when administered with potentially nephrotoxic agents, such as capreomycin.
    Ethacrynic Acid: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to capreomycin may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. Ototoxicity from furosemide or other loop diuretics, while uncommon, can be a transient or permanent side effect of significance. Ototoxicity is best documented with the loop diuretics ethacrynic acid and furosemide, but may also occur with either bumetanide or torsemide. The exact mechanism by which furosemide or other loop diuretics produce ototoxicity is unknown. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended dosages or infusion rates, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If loop diuretics and capreomycin are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Ethambutol: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and ethambutol could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Ethionamide: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and ethionamide could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Etodolac: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Etomidate: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Fenoprofen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Flurbiprofen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Foscarnet: (Major) Because capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including foscarnet, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Fospropofol: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Furosemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to capreomycin may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. Ototoxicity from furosemide or other loop diuretics, while uncommon, can be a transient or permanent side effect of significance. Ototoxicity is best documented with the loop diuretics ethacrynic acid and furosemide, but may also occur with either bumetanide or torsemide. The exact mechanism by which furosemide or other loop diuretics produce ototoxicity is unknown. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended dosages or infusion rates, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If loop diuretics and capreomycin are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Ganciclovir: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    General anesthetics: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Halothane: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like capreomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    Hydrocodone; Ibuprofen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Ibuprofen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Ibuprofen; Famotidine: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Ibuprofen; Oxycodone: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Ibuprofen; Pseudoephedrine: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like capreomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    IncobotulinumtoxinA: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin.
    Indomethacin: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Isoflurane: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Isoniazid, INH: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and isoniazid, INH could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered. (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and isoniazid, INH could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Isoniazid, INH; Rifampin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered. (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and isoniazid, INH could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Ketamine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Ketoprofen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Ketorolac: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Lansoprazole; Naproxen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Lidocaine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lidocaine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Lidocaine; Epinephrine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lidocaine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Lidocaine; Prilocaine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lidocaine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Lithium: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lithium could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Loop diuretics: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to capreomycin may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. Ototoxicity from furosemide or other loop diuretics, while uncommon, can be a transient or permanent side effect of significance. Ototoxicity is best documented with the loop diuretics ethacrynic acid and furosemide, but may also occur with either bumetanide or torsemide. The exact mechanism by which furosemide or other loop diuretics produce ototoxicity is unknown. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended dosages or infusion rates, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If loop diuretics and capreomycin are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Meclofenamate Sodium: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Mefenamic Acid: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Meloxicam: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Nabumetone: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Naproxen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Naproxen; Esomeprazole: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Naproxen; Pseudoephedrine: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Neuromuscular blockers: (Minor) Concomitant use of neuromuscular blockers and capreomycin may prolong neuromuscular blockade. A partial neuromuscular blockade was demonstrated after large intravenous doses of capreomycin.
    Non-Ionic Contrast Media: (Major) Because the use of other nephrotoxic drugs, including capreomycin, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible. Monitor patients for changes in renal function if these drugs are coadministered.
    Nonsteroidal antiinflammatory drugs: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    OnabotulinumtoxinA: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin.
    Oxaprozin: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Pamidronate: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including pamidronate, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Piroxicam: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Polymyxin B: (Major) The concomitant use of capreomycin and polymyxin B may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration of capreomycin with other potentially nephrotoxic drugs, including polymyxin B, may increase serum concentrations of either capreomycin or polymyxin B. Coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function; monitor for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Polymyxin B has also been reported to interfere with nerve transmission at the neuromuscular junction. Avoid coadministration if possible; however, if these drugs must be coadministered, use extreme caution.
    Procainamide: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Procainamide could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Procaine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Procaine hydrochloride could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Propofol: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Quinidine: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Quinidine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Rifabutin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Rifampin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Rifamycins: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Rifapentine: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and any of the rifamycins could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    RimabotulinumtoxinB: (Moderate) The effects of Botulinum Toxins could be potentiated by drugs that interfere with neuromuscular transmission, such as capreomycin.
    Rofecoxib: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Salicylates: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Sevoflurane: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Sulindac: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Sumatriptan; Naproxen: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Tacrolimus: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including tacrolimus, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Tolmetin: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Torsemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to capreomycin may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. Ototoxicity from furosemide or other loop diuretics, while uncommon, can be a transient or permanent side effect of significance. Ototoxicity is best documented with the loop diuretics ethacrynic acid and furosemide, but may also occur with either bumetanide or torsemide. The exact mechanism by which furosemide or other loop diuretics produce ototoxicity is unknown. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended dosages or infusion rates, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If loop diuretics and capreomycin are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Valacyclovir: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including valacyclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are administered concurrently.
    Valdecoxib: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Vancomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration of with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Zoledronic Acid: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including zoledronic acid, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.

    PREGNANCY AND LACTATION

    Pregnancy

    The safety of the use of capreomycin in pregnancy has not been established. Use capreomycin during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. Capreomycin has been shown to be teratogenic in rats when given in doses 3.5 times the human dose. In teratology studies, a low incidence of "wavy ribs" was noted in litters of female rats treated with daily doses of capreomycin 50 mg/kg or more.[44155]

    It is unknown whether capreomycin is excreted in human milk. Use caution when capreomycin is administered to a breast-feeding woman. If capreomycin is ingested, toxicity would be unlikely because it is poorly absorbed (less than 1%) from an intact gastrointestinal system.[44155] Capreomycin use as part of multidrug regimens to treat 2 pregnant women with multidrug-resistant tuberculosis, 1 throughout pregnancy and postpartum and the other postpartum only, has been reported. The infants were breast-fed and developing normally except for a mild speech delay in 1 infant and hyperactivity in the other.[48384]

    MECHANISM OF ACTION

    Capreomycin is a cyclic polypeptide antimycobacterial agent that demonstrates bactericidal activity against strains of Mycobacterium tuberculosis. The exact mechanism of action of capreomycin is not fully understood. It has been theorized that capreomycin interacts with the bacterial ribosome, ultimately inhibiting protein synthesis in a mechanism similar to that of aminoglycosides.
     
    Mutations in the genes for ribosomal RNA have led to capreomycin resistant species of Mycobacterium tuberculosis. As a result of these mutations, cross-resistance has been observed between capreomycin, viomycin, and kanamycin. Cross-resistance between capreomycin and neomycin has also been reported, though to a varying degree. No cross-resistance has been identified between capreomycin and isoniazid, streptomycin, cycloserine, aminosalicylic acid, ethionamide, or ethambutol.

    PHARMACOKINETICS

    Capreomycin is administered intravenously or intramuscularly. Based on a small pharmacokinetic study (n = 7), the mean volume of distribution is approximately 0.4 L/kg +/- 0.9 L/kg in patients with normal renal function. Metabolism is negligible. Approximately 52% of capreomycin is excreted unchanged in the urine within 12 hours of administration. The serum half-life inversely relates to renal function as measured by creatinine clearance. For patients with normal renal function, serum half-life is approximately 5.2—6.8 hours.

    Oral Route

    Oral administration of capreomycin is not feasible due to insignificant absorption from the gastrointestinal tract.

    Intravenous Route

    In 6 healthy volunteers, capreomycin was administered by intravenous and intramuscular route. The area under the serum concentration versus time curve was similar for the two routes; however, peak concentrations were roughly 30% higher after IV infusion administration.

    Intramuscular Route

    Mean peak serum concentrations are 28—32 mcg/mL (range, 20—47 mcg/mL) and are generally achieved 1—2 hours after intramuscular administration in patients with normal renal function. No significant accumulation was seen in patients with normal renal function after 30 days of consecutive 1 g doses. Serum concentration at 24 hours post-dose appears to be low, with an average concentration of 0.95 mcg/mL noted in a small pharmacokinetic study (n = 10).