streptomycin sulfate

Available forms
Available by prescription only
Injection: 400 mg/ml
Lyophilized cake/powder for injection: 200 mg/ml

Indications and dosages
 Tuberculosis. Adults: 1 g or 15 mg/kg I.M. daily or 25 to 30 mg/kg (up to 1.5 g) two to three times weekly for at least 1 year.
Elderly patients: Reduce daily doses based on age, renal function, and eighth cranial nerve function. Suggested dosage is 10 mg/kg (up to 750 mg) daily.
Children: 20 to 40 mg/kg (up to 1 gram) I.M. daily or 25 to 30 mg/kg (up to 1.5 g) two to three times weekly for at least 1year.
 Enterococcal endocarditis. Adults: 1 g I.M. q 12 hours for 2 weeks; then 500 mg I.M. q 12 hours for 4 weeks with penicillin.
 Tularemia. Adults: 1 to 2 g I.M. daily in divided doses for 7 to 14 days or until patient is afebrile for 5 to 7 days.
 Plague. Adults: 2 g (30 mg/kg) I.M. daily in two divided doses for at least 10 days.
Children: 30 mg/kg daily I.M. in two to three divided doses for 10 days.
 Brucellosis. Adults: 1g I.M. once or twice daily with doxycycline or tetracycline during the first week and once daily for at least one more week.
Children older than age 8: 20 mg/kg (up to 1 g) I.M. for 2 weeks in combination with tetracycline.
 Penicillin-susceptible streptococcal endocarditis. Adults age 60 and younger: 1 g I.M. b.i.d. for 1 week with a penicillin. Then 500 mg b.i.d. for 1 week.
Adults older than age 60: 500 mg b.i.d. for 2 weeks with a penicillin.
≡ Dosage adjustment. Dose and frequency modified based on serum levels, which shouldn’t peak above 20 to 25 mcg/ml. If serum levels aren’t available, dosage may be based on creatinine clearance. After 1-g loading dose, patients with creatinine clearance of 50 to 80 ml/minute receive 7.5 mg/kg at 24 hour intervals. For those with clearance of 10 to 50 ml/minute, increase interval to q 24 to 72 hours. Those with clearance below 10 ml/minute may need interval of 72 to 96 hours.
 If patient has renal failure and receives hemodialysis, some clinicians suggest supplemental doses of 50% to 75% of the loading dose at the end of each dialysis period. However, serum levels should be monitored and dosage adjusted to maintain a desired level.

Pharmacodynamics
Antibiotic action: Streptomycin is bactericidal; it binds directly to the 30S ribosomal subunit, inhibiting bacterial protein synthesis. Its spectrum of activity includes many aerobic gram-negative organisms and some aerobic gram-positive organisms. Streptomycin is generally less active against many gram-negative organisms than is tobramycin, gentamicin, amikacin, or netilmicin. Streptomycin is also active against Mycobacterium and Brucella species.

Pharmacokinetics
Absorption: Usually given by deep I.M. injection.
Distribution: Widely distributed after parenteral administration; intraocular penetration is poor. CSF penetration is low, even in patients with inflamed meninges. Streptomycin crosses the placental barrier and is 36% protein-bound.
Metabolism: Not metabolized.
Excretion: Excreted primarily in urine by glomerular filtration; small amounts may be excreted in bile and breast milk. Elimination half-life in adults is 2 to 3 hours. In severe renal damage, half-life may extend to 110 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other aminoglycosides and in those with labyrinthine disease. Never administer I.V. Use cautiously in elderly patients and patients with impaired renal function or neuromuscular disorders.

Interactions
Drug-drug. Amphotericin B, capreomycin, cephalosporins, cisplatin, methoxyflurane, polymyxin B, vancomycin, and other aminoglycosides: Increases risk of nephrotoxicity, ototoxicity, and neurotoxicity. Avoid concurrent or sequential use.
Bumetanide, ethacrynic acid, furosemide, mannitol, urea: Increases risk of ototoxicity. Use together cautiously.
Dimenhydrinate, other antiemetic and antivertigo drugs: May mask streptomycin-induced ototoxicity. Use together cautiously.
General anesthetics or neuromuscular blockers, such as succinylcholine and tubocurarine: Streptomycin may potentiate neuromuscular blockade. Monitor patient closely.
Penicillin: Causes synergistic bactericidal effect against Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Citrobacter, Enterobacter, Klebsiella, and Serratia organisms; however, drugs are physically and chemically incompatible and are inactivated when mixed or given together. Don’t use together.

Adverse reactions
CNS: neuromuscular blockade.
EENT: ototoxicity.
GI: vomiting, nausea.
GU: nephrotoxicity (not as often as other aminoglycosides).
Hematologic: eosinophilia, leukopenia, thrombocytopenia.
Respiratory: apnea.
Skin: exfoliative dermatitis.
Other: hypersensitivity reactions (rash, fever, urticaria, angioedema), anaphylaxis.

Effects on lab test results
• May increase BUN, creatinine, and nonprotein nitrogen levels.
• May increase eosinophil count. May decrease hemoglobin and WBC and platelet counts.

Overdose and treatment
Effects of overdose include ototoxicity, nephrotoxicity, and neuromuscular toxicity.
 Remove drug by hemodialysis or peritoneal dialysis. Treatment with calcium salts or anticholinesterases reverses neuromuscular blockade.

Special considerations
• Protect hands when preparing drug because it irritates skin.
• In primary tuberculosis therapy, discontinue streptomycin when sputum culture is negative.
• Because streptomycin is dialyzable, patients undergoing hemodialysis may need dose adjustments.
• Check blood for peak streptomycin level 1 to 2 hours after I.M. injection; for trough levels, blood should be drawn just before next dose. Don’t use heparinized tube because heparin is incompatible with aminoglycosides.
• Streptomycin may cause false-positive reaction in copper sulfate test for urine glucose (Benedict’s reagent or Clinitest).
Pregnant patients
• Aminoglycosides have caused fetal harm.
Pediatric patients
• Use cautiously and at reduced doses in premature and full-term neonates because of renal immaturity.

Patient education
• Instruct patient to report adverse reactions promptly.
• Encourage adequate fluid intake.
• Emphasize the need for blood tests to monitor streptomycin levels and determine the effectiveness of therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use