CAPREOMYCIN
NB: WHO have issued a rapid guidance in August 2018 with substantive changes to all treatment groups in the last 2016 MDR guidance advising that capreomycin and kanamycin should not be used in MDR TB. Amikacin is still within their guidance but this is now downgraded to a group C medication with Bedaquiline now being upgraded to a group A drug. However given that these new guidelines need to be agreed to be implemented locally and nationally, individual cases should still be managed with expert MDR advice and also in conjunction with the BTS MDR Clinical Advice Service review.
DOSAGE
Capreomycin is usually given once daily for an initial period (usually at least two months), then the frequency may be reduced to three times weekly.
Licensed for intramuscular administration only. There is experience of using capreomycin as an intravenous infusion. (Diluted in 100 mL of 0.9% Sodium Chloride or glucose 5% and administered over 30 to 60 minutes.)
Adults: 15mg/kg daily (usual maximum 1g daily, but can be increased if necessary in large muscular adults). After initial period: 15mg/kg three times per week.
Age >59 years: 10mg/kg daily (maximum 750mg daily). After initial period: 10mg/kg three times per week.
Renal failure: 12-15mg/kg TWO to THREE times a week. Please discuss with a pharmacist.
Obesity: It has been suggested that markedly obese patients should have an adjusted dose using ideal body weight plus 40% of the excess weight in markedly obese patients. The adjusted dose is due to the decreased distribution of extracellular fluids in adipose tissues.
Children: 15-30mg/kg daily (usual maximum 1g daily). After initial period: 15-30mg/kg three times per week.
PREPARATIONS
Parenteral: 1g powder for injection.
DRUG LEVEL MONITORING
Drug levels cannot currently be performed for capreomycin in the UK.
ADVERSE EFFECTS
COMMON:
Nephrotoxicity: Higher risk with prolonged use.
Ototoxicity: Auditory > vestibular (Maybe lower risk than with amikacin; higher risk with prolonged use and older age).
Drug-induced eosinophilia: Usually subsides with intermittent dosing.
SERIOUS:
Dermatological: Induration and local pain with IM injection.
Endocrine: Hypocalcaemia, hypomagnesaemia, and hypokalaemia.
Hepatic: Liver function test abnormalities when used with other anti-TB drugs.
Neurological: Neuromuscular blockade and respiratory paralysis (more common in neuromuscular disease; usually with rapid IV infusion).
Audiological: Ototoxicity - auditory > vestibular (Maybe less than with amikacin; higher with prolonged use and older age).
Renal: Nephrotoxicity (higher with prolonged use).
ADVERSE EFFECTS: MONITORING
Renal, auditory and vestibular monitoring is essential.
Renal function: Month 1 = twice weekly.
Month 2 = weekly.
Month 3 to end of treatment = fortnightly.
Consider reducing to monthly after cessation of treatment with aminoglycoside, if renal function remains stable.
Consider increasing frequency of monitoring if evidence of renal impairment.
Loss of hearing usually occurs first and is detected by regular audiometric testing. Vertigo, loss of balance and auditory disturbances including tinnitus are also signs of ototoxicity.
Ototoxicity on audiogram is defined as a 20 dB loss from baseline at any one test frequency or a 10 dB loss at any two adjacent test frequencies. If this occurs, Capreomycin should be discontinued or dosing reduced in frequency to avoid further hearing loss, although the hearing loss that has occurred is likely to be permanent. Expert advice should be sought at this point to consider a regimen change.
We recommend that patients have baseline audiometry and then monthly reviews until treatment with aminoglycoside ceases. A final audiometry review should be offered 2 months after the final dose.
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTIONS
Increased risk of nephrotoxicity if given with: aminoglycosides, colistimethate sodium.
Increased risk of ototoxicity if given with: aminoglycosides.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To capreomycin.
Pregnancy: Risk of vestibular or auditory nerve damage to infant if used in second or third trimester.
Cautions:
Renal Disease: Use with caution. Reduce the frequency of dosing and monitor serum concentrations.
Obese: Use ideal weight for height to calculate dose and monitor serum-aminoglycoside levels closely.
Elderly: Nephrotoxicity and ototoxicity common in the elderly; monitor and reduce dose if necessary.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.
Not currently available in the UK.
DOSAGE
Capreomycin is usually given once daily for an initial period (usually at least two months), then the frequency may be reduced to three times weekly.
Licensed for intramuscular administration only. There is experience of using capreomycin as an intravenous infusion. (Diluted in 100 mL of 0.9% Sodium Chloride or glucose 5% and administered over 30 to 60 minutes.)
Adults: 15mg/kg daily (usual maximum 1g daily, but can be increased if necessary in large muscular adults). After initial period: 15mg/kg three times per week.
Age >59 years: 10mg/kg daily (maximum 750mg daily). After initial period: 10mg/kg three times per week.
Renal failure: 12-15mg/kg TWO to THREE times a week. Please discuss with a pharmacist.
Obesity: It has been suggested that markedly obese patients should have an adjusted dose using ideal body weight plus 40% of the excess weight in markedly obese patients. The adjusted dose is due to the decreased distribution of extracellular fluids in adipose tissues.
- Male ideal body weight (kg) = 50 + (2.3 x height in cm above (152.4/2.54))
- Female ideal body weight (kg) = 45.5 + (2.3 x height in cm above (152.4/2.54))
Children: 15-30mg/kg daily (usual maximum 1g daily). After initial period: 15-30mg/kg three times per week.
PREPARATIONS
Parenteral: 1g powder for injection.
DRUG LEVEL MONITORING
Drug levels cannot currently be performed for capreomycin in the UK.
ADVERSE EFFECTS
COMMON:
Nephrotoxicity: Higher risk with prolonged use.
Ototoxicity: Auditory > vestibular (Maybe lower risk than with amikacin; higher risk with prolonged use and older age).
Drug-induced eosinophilia: Usually subsides with intermittent dosing.
SERIOUS:
Dermatological: Induration and local pain with IM injection.
Endocrine: Hypocalcaemia, hypomagnesaemia, and hypokalaemia.
Hepatic: Liver function test abnormalities when used with other anti-TB drugs.
Neurological: Neuromuscular blockade and respiratory paralysis (more common in neuromuscular disease; usually with rapid IV infusion).
Audiological: Ototoxicity - auditory > vestibular (Maybe less than with amikacin; higher with prolonged use and older age).
Renal: Nephrotoxicity (higher with prolonged use).
ADVERSE EFFECTS: MONITORING
Renal, auditory and vestibular monitoring is essential.
Renal function: Month 1 = twice weekly.
Month 2 = weekly.
Month 3 to end of treatment = fortnightly.
Consider reducing to monthly after cessation of treatment with aminoglycoside, if renal function remains stable.
Consider increasing frequency of monitoring if evidence of renal impairment.
Loss of hearing usually occurs first and is detected by regular audiometric testing. Vertigo, loss of balance and auditory disturbances including tinnitus are also signs of ototoxicity.
Ototoxicity on audiogram is defined as a 20 dB loss from baseline at any one test frequency or a 10 dB loss at any two adjacent test frequencies. If this occurs, Capreomycin should be discontinued or dosing reduced in frequency to avoid further hearing loss, although the hearing loss that has occurred is likely to be permanent. Expert advice should be sought at this point to consider a regimen change.
We recommend that patients have baseline audiometry and then monthly reviews until treatment with aminoglycoside ceases. A final audiometry review should be offered 2 months after the final dose.
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTIONS
Increased risk of nephrotoxicity if given with: aminoglycosides, colistimethate sodium.
Increased risk of ototoxicity if given with: aminoglycosides.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To capreomycin.
Pregnancy: Risk of vestibular or auditory nerve damage to infant if used in second or third trimester.
Cautions:
Renal Disease: Use with caution. Reduce the frequency of dosing and monitor serum concentrations.
Obese: Use ideal weight for height to calculate dose and monitor serum-aminoglycoside levels closely.
Elderly: Nephrotoxicity and ototoxicity common in the elderly; monitor and reduce dose if necessary.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.
Not currently available in the UK.