CLINICAL USE

Antibacterial agent:Tuberculosis, in combination with other drugsAdjunct to doxycycline in brucellosis Enterococcal endocarditis

DOSE IN NORMAL RENAL FUNCTION

<40 years and weight >50 kg: 15 mg/kg (maximum 1 g) daily or 3 times a week>40 years and weight <50 kg: 0.5–0.75 g daily or 0.75 g 3 times a weekNon-tuberculosis infections: 1–2 g daily in divided dosesAdjust doses according to levels

PHARMACOKINETICS

  • Molecular weight                           :581.6 (1457.4 as sulphate)
  • %Protein binding                           :34–35
  • %Excreted unchanged in urine     : 29–89
  • Volume of distribution (L/kg)       :0.26
  • half-life – normal/ESRD (hrs)      :2.5/100

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Give every 24–72 hours. Dose according to levels
  • 10 to 20     : Give every 24–72 hours. Dose according to levels
  • <10           : Give every 72–96 hours. Dose according to levels

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Dialysed. Dose as in GFR
  • <10           : mL/min
  • HD                     :Dialysed. Dose as in GFR
  • <10           : mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR
  • <10           : mL/min
  • CAV/VVHD      :Dialysed. Dose as in GFR=10–20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsBotulinum toxin: neuromuscular block enhanced

  • Ciclosporin: increased risk of nephrotoxicityCytotoxics: increased risk of nephrotoxicity and ototoxicity with platinum compoundsLoop diuretics: increased risk of ototoxicityMuscle relaxants: enhanced effects of non-depolarising muscle relaxants and suxamethoniumParasympathomimetics: neostigmine and pyridostigmine antagonised by aminoglycosides
  • Tacrolimus: increased risk of nephrotoxicity

    ADMINISTRATION

    Reconstition

    Dissolve 1 g in 2 or 3 mL water for injection

    Route

    IM, IV

    Rate of Administration

    In 100 mL sodium chloride 0.9% or glucose 5% over 30 minutes

    Comments

    In patients who experience tingling sensations or dizziness during administration, increase the infusion time to 60 minutes

    OTHER INFORMATION

    Available on a named patient basis from PfizerPeak level taken 1 hour post dose and should be in the range 15–40 mg/litre; trough level (taken pre dose) should be <5 mg/litre, or <1 mg/litre in renal impairment or those over 50 years of ageMay be less nephrotoxic than other aminoglycosidesPD peritonitis dose is 20–40 mg/litre/day Risk of side effects increases after a cumulative dose of 100 gstreptomycin (unlicensed product).StRePtOMYCIN (UNLICeNSeD PRODUCt) 687A study in 4 patients used IV streptomycin at a dose of 7–15 mg/kg over 30–60 minutes without any problems, although IV administration did increase risk of toxicityDue to the efficacy of twice weekly therapy, it is recommended that tuberculosis patients with severe renal impairment be given a dose of 750 mg 2–3 times a week for the first 2 months of treatment; trough levels should not exceed 4 mg/L. (Ellard GA. Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis. Am Rev Respir Dis. 1993; 148: 650–5.)Peak serum concentrations in individuals with renal impairment should not exceed 20–25 mcg/mLRisk of severe neurotoxicity, irreversible vestibular damage and cochlear reactions is greatly increased in patients with impaired renal function; optic nerve dysfunction, peripheral neuritis, arachnoiditis and encephalopathy may also occur.

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