STREPTOMYCIN- streptomycin sulfate injection, powder, lyophilized, for solution
X-GEN Pharmaceuticals, Inc.
SPL UNCLASSIFIED
To reduce the development of drug-resistant bacteria and maintain the effectiveness of streptomycin and other antibacterial drugs, streptomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
WARNING
THE RISK OF SEVERE NEUROTOXIC REACTIONS IS SHARPLY INCREASED IN PATIENTS WITH IMPAIRED RENAL FUNCTION OR PRE-RENAL AZOTEMIA. THESE INCLUDE DISTURBANCES OF VESTIBULAR AND COCHLEAR FUNCTION, OPTIC NERVE DYSFUNCTION, PERIPHERAL NEURITIS, ARACHNOIDITIS, AND ENCEPHALOPATHY MAY ALSO OCCUR. THE INCIDENCE OF CLINICALLY DETECTABLE, IRREVERSIBLE VESTIBULAR DAMAGE IS PARTICULARLY HIGH IN PATIENTS TREATED WITH STREPTOMYCIN.
RENAL FUNCTION SHOULD BE MONITORED CAREFULLY; PATIENTS WITH RENAL IMPAIRMENT AND/OR NITROGEN RETENTION SHOULD RECEIVE REDUCED DOSES. THE PEAK SERUM CONCENTRATION IN INDIVIDUALS WITH KIDNEY DAMAGE SHOULD NOT EXCEED 20 TO 25 MCG/ML.
THE CONCURRENT OR SEQUENTIAL USE OF OTHER NEUROTOXIC AND/OR NEPHROTOXIC DRUGS WITH STREPTOMYCIN SULFATE, INCLUDING NEOMYCIN, KANAMYCIN, GENTAMICIN, CEPHALORIDINE, PAROMOMYCIN, VIOMYCIN, POLYMYXIN B, COLISTIN, TOBRAMYCIN AND CYCLOSPORINE SHOULD BE AVOIDED.
THE NEUROTOXICITY OF STREPTOMYCIN CAN RESULT IN RESPIRATORY PARALYSIS FROM NEUROMUSCULAR BLOCKAGE, ESPECIALLY WHEN THE DRUG IS GIVEN SOON AFTER THE USE OF ANESTHESIA OR MUSCLE RELAXANTS.
THE ADMINISTRATION OF STREPTOMYCIN IN PARENTERAL FORM SHOULD BE RESERVED FOR PATIENTS WHERE ADEQUATE LABORATORY AND AUDIOMETRIC TESTING FACILITIES ARE AVAILABLE DURING THERAPY.
DESCRIPTION
Streptomycin is a water-soluble aminoglycoside derived from Streptomyces griseus. It is marketed as the sulfate salt of streptomycin. The chemical name of streptomycin sulfate is D-Streptamine, O -2-deoxy-2-(methylamino)-α-L-glucopyranosyl-(1→2)-O -5-deoxy-3-C -formyl-α-L-lyxofuranosyl-(1→4)-N,N 1 -bis(aminoiminomethyl)-,sulfate (2:3) (salt). The molecular formula for Streptomycin Sulfate is (C21 H39 N7 O12 )2 -3H2 SO4 and the molecular weight is 1457.41
Streptomycin for Injection USP, equivalent to 1 gram streptomycin /vial is supplied as a sterile nonpyrogenic lyophillized cake for intramuscular use after reconstitution. The lyophillized cake may reduce to a powder during shipping.
After reconstitution the pH range for Streptomycin for Injection USP should be between 4.5 and 7 in a solution containing 200 mg of streptomycin activity per mL.
*Each vial of Streptomycin for Injection contains streptomycin sulfate equivalent to 1 gram of streptomycin.
CLINICAL PHARMACOLOGY
Following intramuscular injection of 1 g of streptomycin as the sulfate, a peak serum level of 25 to 50 mcg/mL is reached within 1 hour, diminishing slowly to about 50 percent after 5 to 6 hours.
Appreciable concentrations are found in all organ tissues except the brain. Significant amounts have been found in pleural fluid and tuberculous cavities. Streptomycin passes through the placenta with serum levels in the cord blood similar to maternal levels. Small amounts are excreted in milk, saliva, and sweat.
Streptomycin is excreted by glomerular filtration. In patients with normal kidney function, between 29% and 89% of a single 600 mg dose is excreted in the urine within 24 hours. Any reduction of glomerular function results in decreased excretion of the drug and concurrent rise in serum and tissue levels
Microbiology
Streptomycin sulfate is a bactericidal antibiotic. It acts by interfering with normal protein synthesis.
Streptomycin has been shown to be active against most strains of the following organisms both in vitro and in clinical infection. (See INDICATIONS AND USAGE.):
Brucella (brucellosis),
Calymmatobacterium granulomatis (donovanosis, granuloma inguinale),
Escherichia coli, Proteus spp., Aerobacter aerogenes, Klebsiella pneumoniae, and Enterococcus faecalis in urinary tract infections,
Francisella tularensis ,
Haemophilus ducreyi (chancroid),
Haemophilus influenzae (in respiratory, endocardial, and meningeal infections - concomitantly with another antibacterial agent),
Klebsiella pneumoniae pneumonia (concomitantly with another antibacterial agent),
Mycobacterium tuberculosis ,
Pasteurella pestis
Streptococcus viridans, Enterococcus faecalis (in endocardial infections - concomitantly with penicillin).
SUSCEPTIBILITY TESTS: Diffusion Techniques
Quantitative methods that require measurement of zone diameters give the most precise estimate of the susceptibility of bacteria to antimicrobial agents. One such standard procedure 1 which has been recommended for use with disks to test susceptibility of organisms to streptomycin uses the 10 mcg streptomycin disk. Interpretation involves the correlation of the diameter obtained in the disk test with the minimum inhibitory concentration (MIC) for streptomycin.
INDICATIONS AND USAGE
Streptomycin is indicated for the treatment of individuals with moderate to severe infections caused by susceptibile strains of microorganisms in the specific conditions listed below:
Mycobacterium tuberculosis: The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and the Center for Disease Control recommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH or rifampin resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. In the past when the national rate of primary drug resistance to isoniazid was known to be less than 4% and was either stable or declining, therapy with two and three drug regimens was considered adequate. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered. Streptomycin is also indicated for therapy of tuberculosis when one or more of the above drugs is contraindicated because of toxicity or intolerance. The management of tuberculosis has become more complex as a consequence of increasing rates of drug resistance and concomitant HIV infection. Additional consultation from experts in the treatment of tuberculosis may be desirable in those settings.
Non-tuberculosis infections: The use of streptomycin should be limited to the treatment of infections caused by bacteria which have been shown to be susceptible to the antibacterial effects of streptomycin and which are not amenable to therapy with less potentially toxic agents.
Pasteurella pestis (plague),
Francisella tularensis (tularemia),
Brucella ,
Calymmatobacterium granulomatis (donovanosis, granuloma inguinale),
H. ducreyi (chancroid),
H. influenzae (in respiratory, endocardial, and meningeal infections-concomitantly with another antibacterial agent),
K. pneumoniae pneumonia (concomitantly with another antibacterial agent),
E.coli, Proteus, A. aerogenes, K. pneumoniae, and Enterococcus faecalis in urinary tract infections,
Streptococcus viridans, Enterococcus faecalis (in endocardial infections -concomitantly with penicillin),
Gram-negative bacillary bacteremia (concomitantly with another antibacterial agent).
To reduce the development of drug-resistant bacteria and maintain the effectiveness of streptomycin and other antibacterial drugs, streptomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.