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Pronunciation:

(strep toe MYE sin)

Synonyms:

Streptomycin Sulfate

Generic Available:

Yes

Use:

Part of combination therapy of active tuberculosis; used in combination with other agents for treatment of streptococcal or enterococcal endocarditis, mycobacterial infections, plague, tularemia, and brucellosis

Pregnancy Risk Factor:

Lactation:

Enters breast milk/compatible

Contraindications:

Hypersensitivity to streptomycin or any component of the formulation; pregnancy

Warnings/Precautions:

Use with caution in patients with pre-existing vertigo, tinnitus, hearing loss, neuromuscular disorders, or renal impairment; modify dosage in patients with renal impairment; aminoglycosides are associated with significant nephrotoxicity or ototoxicity; the ototoxicity is directly proportional to the amount of drug given and the duration of treatment; tinnitus or vertigo are indications of vestibular injury and impending bilateral irreversible damage; renal damage is usually reversible

Adverse Reactions:

Frequency not defined.

Cardiovascular: Hypotension

Central nervous system: Neurotoxicity, drowsiness, headache, drug fever, paresthesia

Dermatologic: Skin rash

Gastrointestinal: Nausea, vomiting

Hematologic: Eosinophilia, anemia

Neuromuscular & skeletal: Arthralgia, weakness, tremor

Otic: Ototoxicity (auditory), ototoxicity (vestibular)

Renal: Nephrotoxicity

Respiratory: Difficulty in breathing

Overdosage/Toxicology:

Symptoms of overdose include ototoxicity, nephrotoxicity, and neuromuscular toxicity. The treatment of choice following a single acute overdose appears to be maintenance of urine output of at least 3 mL/kg/hour during the acute treatment phase. Dialysis is of questionable value in enhancing aminoglycoside elimination. If required, hemodialysis is preferred over peritoneal dialysis in patients with normal renal function. Chelation with penicillins is experimental.

Drug Interactions:

Increased/prolonged effect: Depolarizing and nondepolarizing neuromuscular blocking agents

Increased toxicity: Concurrent use of amphotericin may increase nephrotoxicity

Stability:

Depending upon manufacturer, reconstituted solution remains stable for 2-4 weeks when refrigerated; exposure to light causes darkening of solution without apparent loss of potency

Compatibility:

Y-site administration: Compatible: Esmolol

Compatibility in syringe: Compatible: Penicillin G sodium. Incompatible: Heparin. Variable (consult detailed reference): Ampicillin

Compatibility when admixed: Compatible: Bleomycin. Incompatible: Amobarbital, amphotericin B, chlorothiazide, heparin, methohexital, norepinephrine, pentobarbital, phenobarbital, phenytoin, sodium bicarbonate

Mechanism of Action:

Inhibits bacterial protein synthesis by binding directly to the 30S ribosomal subunits causing faulty peptide sequence to form in the protein chain

Pharmacodynamics/Kinetics:

Absorption: I.M.: Well absorbed

Distribution: To extracellular fluid including serum, abscesses, ascitic, pericardial, pleural, synovial, lymphatic, and peritoneal fluids; crosses placenta; small amounts enter breast milk

Protein binding: 34%

Half-life elimination: Newborns: 4-10 hours; Adults: 2-4.7 hours, prolonged with renal impairment

Time to peak: Within 1 hour

Excretion: Urine (90% as unchanged drug); feces, saliva, sweat, and tears (<1%)

Dosage:

Children:

Tuberculosis:

Daily therapy: 20-40 mg/kg/day (maximum: 1 g/day)

Directly observed therapy (DOT): Twice weekly: 20-40 mg/kg (maximum: 1 g)

DOT: 3 times/week: 25-30 mg/kg (maximum: 1 g)

Adults:

Tuberculosis:

Daily therapy: 15 mg/kg/day (maximum: 1 g)

Directly observed therapy (DOT): Twice weekly: 25-30 mg/kg (maximum: 1.5 g)

DOT: 3 times/week: 25-30 mg/kg (maximum: 1 g)

Enterococcal endocarditis: 1 g every 12 hours for 2 weeks, 500 mg every 12 hours for 4 weeks in combination with penicillin

Streptococcal endocarditis: 1 g every 12 hours for 1 week, 500 mg every 12 hours for 1 week

Tularemia: 1-2 g/day in divided doses for 7-10 days or until patient is afebrile for 5-7 days

Plague: 2-4 g/day in divided doses until the patient is afebrile for at least 3 days

Elderly: 10 mg/kg/day, not to exceed 750 mg/day; dosing interval should be adjusted for renal function; some authors suggest not to give more than 5 days/week or give as 20-25 mg/kg/dose twice weekly

Dosing interval in renal impairment:

Clcr 10-50 mL/minute: Administer every 24-72 hours

Clcr<10 mL/minute: Administer every 72-96 hours

Removed by hemo and peritoneal dialysis: Administer dose postdialysis

Administration:

Inject deep I.M. into large muscle mass; may be administered I.V. over 30-60 minutes

Monitoring Parameters:

Hearing (audiogram), BUN, creatinine; serum concentration of the drug should be monitored in all patients; eighth cranial nerve damage is usually preceded by high-pitched tinnitus, roaring noises, sense of fullness in ears, or impaired hearing and may persist for weeks after drug is discontinued

Reference Range:

Therapeutic: Peak: 20-30 mcg/mL; Trough: <5 mcg/mL; Toxic: Peak: >50 mcg/mL; Trough: >10 mcg/mL

Test Interactions:

False-positive urine glucose with Benedict's solution or Clinitest®; penicillin may decrease aminoglycoside serum concentrations in vitro

Patient Education:

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. This medication can only be given by intramuscular injection. Therapy for TB may last several months. Do not discontinue even if you are feeling better. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause headache or dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or nausea, vomiting, or loss of appetite (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report immediately change in hearing or sense of fullness in ears; pain, weakness, tremors, or numbness in muscles; unusual clumsiness or change in strength or altered gait; change in urinary pattern or back pain; or respiratory difficulty or chest pain. Pregnancy precaution: Do not get pregnant while taking this medication. Consult prescriber for appropriate barrier contraceptive measures.

Dental Health: Effects on Dental Treatment:

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Mental Health: Effects on Mental Status:

May cause drowsiness

Mental Health: Effects on Psychiatric Treatment:

None reported

Dosage Forms:

Injection, powder for reconstitution, as sulfate: 1 g

International Brand Names:

Ambistryn-S® (IN); Estreptomicina Ahimsa® (AR); Estreptomicina® (AR); Estreptomicina CEPA® (ES); Estreptomicina Clariana® (ES); Estreptomicina Klonal® (AR); Estreptomicina L.CH.® (CL); Estreptomicina Normon® (ES); Estreptomicina Northia® (AR); Estreptomicina Reig Jofre® (ES); Estreptomicina Richet® (AR); Novostrep® (ZA); Servistrep® (CH); Solustrep® (ZA); Strep-Deva® (TR); Strepto-Fatol® (DE); Strepto-Hefa® (DE); Streptomicina® (RO); Streptomicina Solfato® (IT); Streptomycin® (BG, HU, RU); Streptomycine IE® (TR); Streptomycine Panpharma® (FR); Streptomycin Grünenthal® (DE); Streptomycin Opsonin® (BD); Streptomycin Renata® (BD); Streptomycin sulfat® (YU); Streptomycin Sulphate® (GB); Streptomycin Sulphate Meiji® (ID, SG); Streptomycinum® (PL); Strepto® (TH)

References

Ad Hoc Committee of the Scientific Assembly on Microbiology, Tuberculosis, and Pulmonary Infections, "Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children,"Clin Infect Dis, 1995, 21:9-27.

American Academy of Pediatrics Committee on Infectious Diseases, "Chemotherapy for Tuberculosis in Infants and Children,"Pediatrics 1992, 89(1):161-5.

Arguedas AG and Wehrle PP, "New Concepts for Antimicrobial Use in Central Nervous System Infections,"Semin Pediatr Infect Dis, 1991, 2(1):36-42.

Balyan FR, Taibah A, De Donato G, et al, "Titration Streptomycin Therapy in Meinere's Disease: Long-Term Results,"Otolaryngol Head Neck Surg, 1998, 118(2):261-6.

Begg EJ and Barclay ML, "Aminoglycosides - 50 Years On,"Br J Clin Pharmacol, 1995, 39(6):597-603.

Cunha BA, "Aminoglycosides: Current Role in Antimicrobial Therapy,"Pharmacotherapy, 1988, 8(6):334-50.

Davidson PT and Le HQ, "Drug Treatment of Tuberculosis - 1992,"Drugs, 1992, 43(5):651-73.

"Drugs for Tuberculosis,"Med Lett Drugs Ther, 1993, 35(908):99-101.

Edson RS and Terrell CL, "The Aminoglycosides,"Mayo Clin Proc, 1999, 74(5):519-28.

Havlir DV and Barnes PF, "Tuberculosis in Patients With Human Immunodeficiency Virus Infection,"N Engl J Med, 1999, 340(5):367-73.

Iseman MD, "Treatment of Multidrug-Resistant Tuberculosis,"N Engl J Med, 1993, 329(11):784-91.

Kim-Sing A, Kays MB, Vivien EJ, et al, "Intravenous Streptomycin Use in a Patient Infected With High-Level Gentamicin-Resistant Streptococcus faecalis,"Ann Pharmacother, 1993, 27(6):712-4.

Lorin MI, Hsu KH, and Jacob SC, "Treatment of Tuberculosis in Children,"Pediatr Clin North Am, 1983, 30(2):333-48.

Morris JT and Cooper RH, "Intravenous Streptomycin: A Useful Route of Administration,"Clin Infect Dis, 1994, 19(6):1150-1.

"Prevention and Treatment of Tuberculosis Among Patients Infected With Human Immunodeficiency Virus: Principles of Therapy and Revised Recommendations. Centers for Disease Control and Prevention,"MMWR Recomm Rep, 1998, 47(RR-20):1-58.

Van Scoy RE and Wilkowske CJ, "Antituberculous Agents,"Mayo Clin Proc, 1992, 67(2):179-87.

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