STREPTOMYCIN
Please note streptomycin is not licensed in the UK.
Streptomycin is not usually recommended for the treatment of MDRTB, as half of UK cases are resistant to streptomycin.
PREPARATIONS
Parenteral: 1g powder for reconstitution for injection (unlicensed medicine).
DOSAGE
For intramuscular administration only. There is experience of using streptomycin as an intravenous infusion, but the prescriber should ensure the streptomycin preparation used is suitable for intravenous administration.
Streptomycin is usually given once daily for an initial period (usually at least two months), then the frequency may be reduced to three times weekly.
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: 15mg/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.
Adjust dose and/or frequency according to serum streptomycin concentration (see below).
Children: 20-40mg/kg daily (maximum 1g daily). After initial period: 20-40mg/kg three times per week.
Adjust dose and/or frequency according to serum streptomycin concentration (see below).
DRUG LEVEL MONITORING
Indications for monitoring:
Target Level: <5mg/L (trough)
25 – 35mg/L (peak)
Timing of sample:
COMMON:
Nephrotoxicity: Accumulation if renal impairment.
Ototoxicity: Irreversible vestibulocochlear nerve damage.
Hypersensitivity skin reactions: Rashes, urticaria, erythroderma.
Drug-induced eosinophillia (Usually subsides with intermittent dosing).
SERIOUS:
Endocrine: Hypocalcaemia, hypomagnesaemia, and hypokalaemia
Immunological: Anaphylaxis (uncommon).
Neurological: Neuromuscular blockade and respiratory paralysis (more common in neuromuscular disease; usually dose-related and self-limiting).
Audiological: Ototoxicity - auditory > vestibular (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: End of treatment with an aminoglycoside = 2 weekly
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, Amikacin 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. Of the current injectable agents, Capreomycin may be less ototoxic.
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: capreomycin, cephalosporins, ciclosporin, colistimethate sodium, tacrolimus
Increased risk of ototoxicity if given with: loop diuretics
Increased risk of hypocalcaemia with bisphosphonates.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: to streptomycin or other aminoglycosides
Myasthenia Gravis: as aminoglycosides may impair neuromuscular transmission
Pregnancy: Risk of vestibular or auditory nerve damage to infant if used in second or third trimester
Cautions:
Obese: Use ideal weight for height to calculate dose and monitor serum streptomycin levels closely
Elderly: Nephrotoxicity and ototoxicity common in the elderly; monitor and reduce dose if necessary
Renal Disease: Use with caution. Reduce the frequency of dosing and monitor serum concentrations.
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.
Sample Type: Serum.
Volume Required: 2ml (min 0.1mL).
Sample Container: Plain glass or plastic (non SST).
Container Type: Any.
Availability: Office Hours.
Turnaround Time: Telephoned same day if received 9am-3pm Mon-Fri if advanced warning given. Written confirmation report will be sent by 1st Class post.
The sample must be heat-treated before dispatch if HIV positive.
Streptomycin is not usually recommended for the treatment of MDRTB, as half of UK cases are resistant to streptomycin.
PREPARATIONS
Parenteral: 1g powder for reconstitution for injection (unlicensed medicine).
DOSAGE
For intramuscular administration only. There is experience of using streptomycin as an intravenous infusion, but the prescriber should ensure the streptomycin preparation used is suitable for intravenous administration.
Streptomycin is usually given once daily for an initial period (usually at least two months), then the frequency may be reduced to three times weekly.
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: 15mg/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))
Adjust dose and/or frequency according to serum streptomycin concentration (see below).
Children: 20-40mg/kg daily (maximum 1g daily). After initial period: 20-40mg/kg three times per week.
Adjust dose and/or frequency according to serum streptomycin concentration (see below).
DRUG LEVEL MONITORING
Indications for monitoring:
- Ensure therapeutic dose
- Ensure renal clearance, especially in at risk patients (e.g. renal impairment, elderly)
Target Level: <5mg/L (trough)
25 – 35mg/L (peak)
Timing of sample:
- Pre dose
- 60mins after infusion ends
- Peak serum level in first week, repeat if poor response.
- Trough serum levels weekly for 4 weeks, fortnightly for 4 weeks, then monthly if stable
COMMON:
Nephrotoxicity: Accumulation if renal impairment.
Ototoxicity: Irreversible vestibulocochlear nerve damage.
Hypersensitivity skin reactions: Rashes, urticaria, erythroderma.
Drug-induced eosinophillia (Usually subsides with intermittent dosing).
SERIOUS:
Endocrine: Hypocalcaemia, hypomagnesaemia, and hypokalaemia
Immunological: Anaphylaxis (uncommon).
Neurological: Neuromuscular blockade and respiratory paralysis (more common in neuromuscular disease; usually dose-related and self-limiting).
Audiological: Ototoxicity - auditory > vestibular (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: End of treatment with an aminoglycoside = 2 weekly
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, Amikacin 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. Of the current injectable agents, Capreomycin may be less ototoxic.
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: capreomycin, cephalosporins, ciclosporin, colistimethate sodium, tacrolimus
Increased risk of ototoxicity if given with: loop diuretics
Increased risk of hypocalcaemia with bisphosphonates.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: to streptomycin or other aminoglycosides
Myasthenia Gravis: as aminoglycosides may impair neuromuscular transmission
Pregnancy: Risk of vestibular or auditory nerve damage to infant if used in second or third trimester
Cautions:
Obese: Use ideal weight for height to calculate dose and monitor serum streptomycin levels closely
Elderly: Nephrotoxicity and ototoxicity common in the elderly; monitor and reduce dose if necessary
Renal Disease: Use with caution. Reduce the frequency of dosing and monitor serum concentrations.
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.
Sample Type: Serum.
Volume Required: 2ml (min 0.1mL).
Sample Container: Plain glass or plastic (non SST).
Container Type: Any.
Availability: Office Hours.
Turnaround Time: Telephoned same day if received 9am-3pm Mon-Fri if advanced warning given. Written confirmation report will be sent by 1st Class post.
The sample must be heat-treated before dispatch if HIV positive.