Актуальная Медицина - STREPTOMYCIN SULFATE (PDH)

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STREPTOMYCIN SULFATE   (PDH)

·      Pharmacologic classification: aminoglycoside

·      Therapeutic classification: antibiotic

·      Pregnancy risk category D

 

How supplied

            Available by prescription only

            Injection: 400 mg/ml, 1g/vial, 5g/vial

 

Indications, route and dosage

            Primary and adjunctive treatment in tuberculosis

            Adults with normal renal function: 1 g I.M. daily for 2 to 3 months, then 1 g two or three times a week. Inject deeply into upper outer quadrant of buttocks.

            Children with normal renal function: 20 mg/kg i.m. daily in divided doses injected deeply into large muscle mass. Give concurrently with other antitubercular agents, but not with capreomycin, and continue until sputum specimen becomes negative.

 

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 injected deeply into upper outer quadrant of buttocks. Continue until patient is afebrile for 5 to 7 days.

Dosage in renal failure

            Adults and children: Initial dosage is same as for those with normal renal function. Subsequent doses and frequency determined by renal function study results and blood serum concentrations; keep peak serum levels between 5 and 25 mcg/ml, and through levels below 5 mcg/ml. Patients with a creatinine clearance > 50 ml/min usually can tolerate the drug daily; if creatinine clearance is 10 to 50 ml/min, administration interval is increased to every 24 to 72 hours. Patients with a creatinine clearance < 10 ml/min may require 72 to 96 hours between doses.

 

Pharmacodynamics

            Antibiotic action: Streptomycin is bactericidal; it binds directly to the  ribosomal subunit, thus inhibiting bacterial protein synthesis.

 

Pharmacokinetics

·      Absorption: Streptomycin is absorbed poorly after oral administration and usually is given parenterally; peak serum concentrations occur 1 to 2 hours after I.M. administration.

 

Contraindications and precautions

            Streptomycin is contraindicated in patients with known hypersensitivity to streptomycin or any other aminoglycoside.

            Streptomycin should be used cautiously in patients with decreased renal function; in patients with tinnitus, vertigo, and high frequency hearing loss who are susceptible to ototoxicity; in patients with dehydration, myasthenia gravis, parkinsonism, and hypocalcemia; in neonates and other infants; and in elderly patients.

 

Interactions

 

            Concomitant use with the following drugs may increase the hazard of nephrotoxicity, ototoxicity and neurotoxicity: methoxyflurane, polymyxin B, vancomycin, capreomycin, cisplatin, cephalosporins, amphotericin B, and other aminoglycosides; hazard of ototoxicity is also increased during use with ethacrynic acid, furosemide, bumetanide, urea, or mannitol. Dimenhydrinate and other antiemetic and antivertigo drugs may mask streptomycin-induced ototoxicity.

            Concomitant use with penicillins results in synergistic bactericidal effect against Pseudomonas aeruginisa, Escherichia coli, Klebsiella, Citrobacter, Enterobacter, Serratia, and Proteus mirabilis; however, the drugs are physically and chemically incompatible and are inactivated when mixed or given together. In vivo inactivation has been reported when aminoglycosides and penicillins are used concomitantly.

            Streptomycin may potentiate neuromuscular blockade from general anesthetics or neuromuscular blocking agents such as succinylcholine and tubocurarine.

 

Effects on diagnostic tests

            Streptomycin may cause false-positive reaction in copper sulfate test for urine glucose (Benedict’s reagent or Clinitest).

            Streptomycin-induced nephrotoxicity may elevate levels of blood urea nitrogen, nonprotein nitrogen, or serum creatinine levels and increase urinary excretion of casts.

 

Adverse reactions

·      CNS: headache, lethargy.

·      EENT: ototoxicity (tinnitus, vertigo, hearing loss).

·      GI: diarrhea.

·      GU: some nephrotoxicity (less frequent than with other aminoglycosides).

·      HEMA: transient agranulocytosis.

·      Local: pain, irritation, and sterile abscesses at injection site.

·      Other: hypersensitivity reactions (rash, fever, urticaria, angioneurotic edema, anaphylaxis), bacterial and fungal superinfection, neuromuscular blockade.

Note: Drug should be discontinued if patient shows signs of ototoxicity, nephrotoxicity, or hypersensitivity or if severe diarrhea indicates pseudomembranous colitis.

Overdose and treatment

Clinical sings 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

            Besides those relevant to all aminoglycosides, consider the following recommendations:

·      Protect hands when preparing drug; drug irritates skin.

·      In primary tuberculosis therapy, discontinue streptomycin when sputum test is negative.

·      Because streptomycin is dialyzable, patients undergoing hemodialysis may need dosage adjustments.

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