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    Aminoglycoside Antibiotics
    Antibiotics for Tuberculosis

    BOXED WARNING

    Hearing impairment, infants, neurotoxicity, ototoxicity, renal failure, renal impairment, requires a specialized care setting, tinnitus

    The risk of severe neurotoxicity is sharply increased in patients with renal impairment or prerenal azotemia. Monitor renal function carefully; reduce the streptomycin dose in patients with renal impairment and/or nitrogen retention. Do not exceed a peak serum streptomycin concentration of 20 to 25 mcg/mL in patients with kidney damage. Avoid the concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with streptomycin. Streptomycin-induced neurotoxicity can result in respiratory paralysis from neuromuscular blockade, especially when the drug is given soon after the use of anesthesia or muscle relaxants. A syndrome of apparent central nervous system depression, characterized by stupor and flaccidity, occasionally coma and deep respiratory depression, has been reported in very young infants in whom streptomycin dosage had exceeded the recommended limits; do not exceed the recommended streptomycin dosage in infants. Parenteral use of streptomycin requires a specialized care setting where adequate laboratory and/or audiometric testing facilities are available during therapy. Both vestibular and auditory dysfunction can follow the administration of streptomycin. Vestibular dysfunction resulting from the parenteral administration of streptomycin is cumulatively related to the total daily dose. When 1.8 to 2 g/day are given, symptoms are likely to develop in a large percentage of patients, especially in patients with renal impairment, within 4 weeks. Therefore, it is recommended that caloric and audiometric tests be done before, during, and after intensive therapy with streptomycin to facilitate detection of any vestibular dysfunction and/or impairment of hearing which may occur. Tinnitus, roaring noises, or a sense of fullness in the ears indicates the need for audiometric examination or termination of streptomycin therapy or both. The degree of impairment is directly proportional to the dose and duration of streptomycin administration, the age of the patient, the level of renal function, and the amount of underlying existing hearing impairment. The ototoxic effects of the aminoglycosides, including streptomycin, are potentiated by the coadministration of other ototoxic drugs. The vestibulotoxic potential of streptomycin exceeds that of its capacity for cochlear toxicity. Appropriate monitoring and early discontinuation of the drug may permit recovery before irreversible damage to the sensorineural cells. Use extreme caution in selecting a dosage regimen in the presence of preexisting renal impairment or renal failure. In patients with severe uremia, a single dose may produce high blood concentrations for several days, and the cumulative effect may produce ototoxic sequelae. When streptomycin must be given for prolonged periods, alkalinization of the urine may minimize or prevent renal irritation.[30007]

    DEA CLASS

    Rx

    DESCRIPTION

    Aminoglycoside antibiotic; due to resistant organisms, increased risk of irreversible vestibular toxicity, and the inability to monitor serum concentration, other aminoglycoside agents are more desirable.

    HOW SUPPLIED

    Streptomycin/Streptomycin Sulfate Intramuscular Inj Pwd F/Sol: 1g

    DOSAGE & INDICATIONS

    For the treatment of brucellosis in combination with other antimicrobials.
    For brucellosis caused by Brucella sp. in combination with tetracycline.
    Intramuscular dosage
    Adults

    Tetracycline 500 mg PO every 6 hours for 3 weeks in combination with streptomycin 1 g IM twice daily for the first week, then streptomycin 1 g IM once daily for the second week.

    Intramuscular dosage
    Adults

    1—2 g IM per day in divided doses every 6—12 hours.

    Infants, Children, and Adolescents

    20—40 mg/kg/day IM in divided doses every 6—12 hours, not to exceed adult doses.

    For the treatment of gram-negative bacillary bacteremia, meningitis, or lower respiratory tract infections (e.g., pneumonia) in combination with other antimicrobials.
    Intramuscular dosage
    Adults

    1—2 g IM per day in divided doses every 6—12 hours.

    Infants, Children, and Adolescents

    20—40 mg/kg/day IM in divided doses every 6—12 hours, not to exceed adult doses.

    For the treatment of urinary tract infection (UTI) due to E. coli, Proteus sp., E. aerogenes, K. pneumoniae, or E. faecalis in combination with other antimicrobials.
    Intramuscular dosage
    Adults

    1—2 g IM per day in divided doses every 6—12 hours.

    Infants, Children, and Adolescents

    20—40 mg/kg/day IM in divided doses every 6—12 hours, not to exceed adult doses.

    For the treatment of chancroid or granuloma inguinale in combination with other antimicrobials.
    Intramuscular dosage
    Adults

    Not recommended by guidelines. 1 to 2 g/day IM divided every 6 to 12 hours.

    Infants, Children, and Adolescents

    Not recommended by guidelines. 20 to 40 mg/kg/day (Max: 2 g/day) IM divided every 6 to 12 hours.

    For the treatment of infective endocarditis.
    NOTE: Serum streptomycin concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight. Adjust the streptomycin dose to maintain peak serum concentrations of 20 to 35 mcg/mL and trough concentrations of less than 10 mcg/mL. Avoid streptomycin use in patients with a CrCl less than 50 mL/minute.
    Intravenous or Intramuscular dosage
    Adults

    15 mg/kg/day IV or IM divided every 12 hours. Clinical practice guidelines recommend streptomycin in combination with ampicillin or penicillin G as an alternative for penicillin-susceptible, gentamicin-resistant enterococcal endocarditis. Treat for 4 to 6 weeks for native valve endocarditis and for 6 weeks for prosthetic valve endocarditis.

    For the treatment of drug-susceptible tuberculosis infection as part of combination therapy.
    NOTE: Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for dosing in patients with marked obesity.
    For the treatment of drug-susceptible tuberculosis infection in persons without HIV as part of combination therapy.
    Intravenous† or Intramuscular dosage
    Adults

    15 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max: 1.5 g/dose) IV or IM 3 days/week or twice weekly.[30007] [61094] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Use adjusted body weight in obese patients.[65645] Streptomycin is generally recommended as second-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Infants, Children, and Adolescents

    15 to 40 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max 1.5 g/dose) IV or IM 3 days/week or twice weekly. [61094] Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients. Streptomycin is generally used as second-line therapy. Duration is dependent on the site of involvement.

    Neonates†

    20 to 40 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Streptomycin is generally recommended as part of the initial 2-month intensive phase of treatment for susceptible infections.[53484] [53485] [61095] [65675]

    For the treatment of drug-susceptible tuberculosis infection in persons with HIV as part of combination therapy.
    Intravenous† or Intramuscular dosage
    Adults

    15 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max 1.5 g/dose) IV or IM 3 days/week.[30007] [34362] [61094] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Use adjusted body weight in obese patients.[65645] Use adjusted body weight in obese patients.[65645] Streptomycin is recommended as second-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Adolescents

    15 to 40 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max 1.5 g/dose) IV or IM 3 days/week.[30007]   Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients. Streptomycin is generally recommended as second-line therapy; duration is dependent on the site of involvement.

    Infants and Children

    15 to 40 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week.  [61094] Daily dosing is defined as 5- or 7 days/week. Use adjusted body weight in obese patients. Streptomycin is generally recommended as second-line therapy; duration is dependent on the site of involvement.

    Neonates†

    20 to 40 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Streptomycin is generally recommended as part of the initial 2-month intensive phase of treatment for susceptible infections.[53484] [53485] [61095] [65675]

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy.
    NOTE: Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for dosing in patients with marked obesity.
    For the treatment of drug-resistant tuberculosis infection as part of combination therapy in persons without HIV.
    Intravenous† or Intramuscular dosage
    Adults

    15 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max: 1.5 g/dose) IV or IM 3 days/week or twice weekly.[30007] Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients.

    Infants, Children, and Adolescents

    15 to 40 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max 1.5 g/dose) IV or IM 3 days/week or twice weekly. Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients.

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy in persons living with HIV.
    Intravenous† or Intramuscular dosage
    Adults

    15 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max 1.5 g/dose) IV or IM 3 days/week.[30007] Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients. Use adjusted body weight in obese patients.

     Adolescents

    15 to 40 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max 1.5 g/dose) IV or IM 3 days/week.[30007] Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients. Use adjusted body weight in obese patients.

    Infants and Children

    15 to 40 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week. Daily dosing is defined as 5- or 7 days/week. Use adjusted body weight in obese patients.

    For the treatment of plague infection due to exposure to Yersinia pestis in an individual patient or in a contained casualty setting.
    NOTE: It is recommended that pregnant women be treated with gentamicin as a first-line agent; streptomycin has been associated with deafness in children following fetal exposure and should be avoided if possible.
    Intramuscular dosage
    Adults

    1 g IM every 12 hours for 10 days. If antibiotic susceptibility testing allows, intravenous gentamicin or, as third-line agents, intravenous doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives.

    Infants, Children, and Adolescents

    15 mg/kg IM every 12 hours, not to exceed 2 g/day, for 10 days. If antibiotic susceptibility testing allows, intravenous gentamicin or, as third-line, intravenous doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives.

    For the initial treatment of tularemia infection due to exposure to Francisella tularensis.
    In an individual patient or in a contained casualty setting.
    NOTE: It is recommended that pregnant women be treated with gentamicin as a first-line agent. Streptomycin has been associated with deafness in children following fetal exposure and should be avoided if possible; however, the risk of serious infection supports the use of streptomycin as a preferred treatment if gentamicin is contraindicated.
    Intramuscular dosage
    Adults

    1 g IM every 12 hours for 10 days. If antibiotic susceptibility testing allows, intravenous gentamicin or, as third-line agents, intravenous doxycycline, chloramphenicol, or ciprofloxacin could be used as alternatives. The risk of serious infection following tularemia exposure supports the use of streptomycin as initial therapy in pregnant women; change to alternatives when possible. Women who are breast-feeding should be treated with the same antibiotic as the infant.

    Infants, Children, and Adolescents

    15 mg/kg IM every 12 hours, not to exceed 2 g/day, for 10 days. If antibiotic susceptibility testing allows, intravenous gentamicin or, as third-line, intravenous doxycycline, chloramphenicol, or ciprofloxacin could be used as alternatives.

    In a mass casualty setting and for tularemia prophylaxis† following exposure to Francisella tularensis.
    NOTE: Doxycycline and ciprofloxacin are preferred agents in this setting, although, streptomycin can be used as an alternative.
    Intramuscular dosage
    Adults

    1 g IM every 12 hours. If treatment is begun in the incubation period of tularemia and continued daily for 14 days, exposed individuals might be protected against symptomatic infection. The risk of serious infection following tularemia exposure supports the use of streptomycin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of doxycycline or ciprofloxacin.

    Infants, Children, and Adolescents

    15 mg/kg IM every 12 hours, not to exceed 2 g/day. If treatment is begun in the incubation period of tularemia and continued daily for 14 days, exposed individuals might be protected against symptomatic infection. The risk of serious infection following tularemia exposure supports the use of streptomycin if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the use of doxycycline or ciprofloxacin.

    For the treatment of Mycobacterium avium complex infection† (MAC) in persons with HIV.
    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM once daily plus clarithromycin or azithromycin and ethambutol. May consider addition of streptomycin as a third or fourth drug (or rifabutin, amikacin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    Adolescents

    1 g IV or IM once daily plus clarithromycin or azithromycin and ethambutol. May consider addition of streptomycin as a third or fourth drug (or rifabutin, amikacin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    For the treatment of actinomycotic mycetoma†.
    For actinomycotic mycetoma† caused by Actinomadura madurae or Streptomyces somaliensis.
    Intramuscular dosage
    Adults

    14 mg/kg/day IM for the first month and then on alternate days in combination with dapsone. If no response after 1 month, dapsone should be replaced with co-trimoxazole.

    For actinomycotic mycetoma† caused by Actinomadura pelletierii or Nocardia brasiliensis.
    Intramuscular dosage
    Adults

    14 mg/kg/day IM for the first month and then on alternate days in combination with co-trimoxazole.

    For the treatment of bartonellosis†, including chronic verruga peruana†.
    Intramuscular dosage
    Adults

    15 to 20 mg/kg/day IM for 10 to 21 days.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2 g/day IM; 1 g/day IV once daily or 5 days/week or 1.5 g/day IV 3 days/week or twice weekly has been used off-label.

    Geriatric

    2 g/day IM; 1 g/day IV once daily or 5 days/week or 1.5 g/day IV 3 days/week or twice weekly has been used off-label.

    Adolescents

    40 mg/kg/day (Max: 2 g/day) IM; 40 mg/kg/day (Max: 1 g/day) IV once daily or 5 days/week or 25 to 30 mg/kg/day (Max 1.5 g/day) IV 3 days/week or twice weekly has been used off-label.

    Children

    40 mg/kg/day (Max: 2 g/day) IM; 40 mg/kg/day (Max: 1 g/day) IV once daily or 5 days/week or 25 to 30 mg/kg/day (Max 1.5 g/day) IV 3 days/week or twice weekly has been used off-label.

    Infants

    40 mg/kg/day IM; 40 mg/kg/day IV once daily or 5 days/week or 25 to 30 mg/kg/day IV 3 days/week or twice weekly has been used off-label.

    Neonates

    Safety and efficacy have not been established; 40 mg/kg/day IM/IV has been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Use extreme caution in selecting a dosage regimen in the presence of preexisting renal insufficiency. Do not exceed a peak serum streptomycin concentration of 20 to 25 mcg/mL in patients with kidney damage.[30007]
     
    Adult patients† [32569]
    CrCl more than 50 mL/minute: Administer the dose every 24 hours.
    CrCl 10 to 50 mL/minute: Administer the dose every 24 to 72 hours.
    CrCl less than 10 mL/minute: Administer the dose every 72 to 96 hours.
     
    Adult tuberculosis patients† [34362] [61094] [65465]
    NOTE: Monitor serum concentrations.
    CrCl 30 mL/minute or more: No dosage adjustment necessary.
    CrCl less than 30 mL/minute: 15 mg/kg IV or IM 3 days/week or twice weekly.
     
    Pediatric patients† [32569]
    GFR more than 50 mL/minute/1.73m2: No dosage adjustment necessary.
    GFR 30 to 50 mL/minute/1.73m2: 7.5 mg/kg/dose IV or IM every 24 hours.
    GFR 10 to 29 mL/minute/1.73m2: 7.5 mg/kg/dose IV or IM every 48 hours.
    GFT less than 10 mL/minute/1.73m2: 7.5 mg/kg/dose IV or IM every 72 to 96 hours.
     
     
    Intermittent hemodialysis†
    Adult patients
    Administer one-half of the normal dose after hemodialysis.[32569]
     
    Adult tuberculosis patients
    15 mg/kg IV or IM 3 days/week or twice weekly; administer after hemodialysis on dialysis days.[34362] [61094] [65465]
     
    Pediatric patients
    7.5 mg/kg/dose IV or IM every 72 to 96 hours.[32569]
     
    Peritoneal dialysis†
    Pediatric patients
    7.5 mg/kg/dose IV or IM every 72 to 96 hours.[32569]
     
    Continuous renal replacement therapy (CRRT)†
    NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303]
     
    Adult patients
    Administer the dose every 24 to 72 hours; monitor serum concentrations.[32569]
     
    Pediatric patients
    7.5 mg/kg/dose IV or IM every 24 hours; monitor serum concentrations.[32569]

    ADMINISTRATION

     
    Tuberculosis patients
    Directly observed therapy (DOT) is recommended for all children as well as adolescents and adults living with HIV and any regimen consisting of intermittent therapy.[34361] [34362] [61094]

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    NOTE: Streptomycin is FDA-approved for intravenous use.
     
    Reconstitution
    Reconstitute vial with Sterile Water for Injection to yield the desired concentration.
    Reconstitute with 4.2 mL for an approximate concentration of 200 mg/mL.
    Reconstitute with 3.2 mL for an approximate concentration of 250 mg/mL.
    Reconstitute with 1.8 mL for an approximate concentration of 400 mg/mL.
    Storage: Reconstituted solutions may be stored at room temperature for 1 week. Protect from light.[30007]
     
    Dilution
    Dilute desired dose in 100 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection.[62793] [62794] [62795] [62796]
    Storage: Diluted solution is stable for 24 hours.[62793]
     
    Intermittent IV infusion†
    Infuse through a peripheral or central IV catheter over 30 to 60 minutes.[62793] [62794] [62795] [62796]

    Intramuscular Administration

    Reconstitution
    Reconstitute vial with Sterile Water for Injection to yield the desired concentration.
    Reconstitute with 4.2 mL for an approximate concentration of 200 mg/mL.
    Reconstitute with 3.2 mL for an approximate concentration of 250 mg/mL.
    Reconstitute with 1.8 mL for an approximate concentration of 400 mg/mL.
    Storage: Reconstituted solutions may be stored at room temperature for 1 week. Protect from light.
     
    Intermitent IM injection
    Inject deeply into a large muscle mass, preferably in the upper outer quadrant of the gluteal region or the muscles of the mid-lateral thigh. In children, the preferable site is the mid-lateral thigh. Use the upper outer quadrant of the gluteal region only when necessary.
    Alternate injection sites.

    STORAGE

    Generic:
    - Protect from light
    - Store unreconstituted product at 68 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Aminoglycoside hypersensitivity

    Streptomycin is contraindicated in patients with a history of clinically significant streptomycin hypersensitivity. Clinically significant aminoglycoside hypersensitivity may also contraindicate streptomycin use because of known cross-sensitivity of patients to drugs in this class.[30007]

    Hearing impairment, infants, neurotoxicity, ototoxicity, renal failure, renal impairment, requires a specialized care setting, tinnitus

    The risk of severe neurotoxicity is sharply increased in patients with renal impairment or prerenal azotemia. Monitor renal function carefully; reduce the streptomycin dose in patients with renal impairment and/or nitrogen retention. Do not exceed a peak serum streptomycin concentration of 20 to 25 mcg/mL in patients with kidney damage. Avoid the concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with streptomycin. Streptomycin-induced neurotoxicity can result in respiratory paralysis from neuromuscular blockade, especially when the drug is given soon after the use of anesthesia or muscle relaxants. A syndrome of apparent central nervous system depression, characterized by stupor and flaccidity, occasionally coma and deep respiratory depression, has been reported in very young infants in whom streptomycin dosage had exceeded the recommended limits; do not exceed the recommended streptomycin dosage in infants. Parenteral use of streptomycin requires a specialized care setting where adequate laboratory and/or audiometric testing facilities are available during therapy. Both vestibular and auditory dysfunction can follow the administration of streptomycin. Vestibular dysfunction resulting from the parenteral administration of streptomycin is cumulatively related to the total daily dose. When 1.8 to 2 g/day are given, symptoms are likely to develop in a large percentage of patients, especially in patients with renal impairment, within 4 weeks. Therefore, it is recommended that caloric and audiometric tests be done before, during, and after intensive therapy with streptomycin to facilitate detection of any vestibular dysfunction and/or impairment of hearing which may occur. Tinnitus, roaring noises, or a sense of fullness in the ears indicates the need for audiometric examination or termination of streptomycin therapy or both. The degree of impairment is directly proportional to the dose and duration of streptomycin administration, the age of the patient, the level of renal function, and the amount of underlying existing hearing impairment. The ototoxic effects of the aminoglycosides, including streptomycin, are potentiated by the coadministration of other ototoxic drugs. The vestibulotoxic potential of streptomycin exceeds that of its capacity for cochlear toxicity. Appropriate monitoring and early discontinuation of the drug may permit recovery before irreversible damage to the sensorineural cells. Use extreme caution in selecting a dosage regimen in the presence of preexisting renal impairment or renal failure. In patients with severe uremia, a single dose may produce high blood concentrations for several days, and the cumulative effect may produce ototoxic sequelae. When streptomycin must be given for prolonged periods, alkalinization of the urine may minimize or prevent renal irritation.[30007]

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including streptomycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Obesity

    Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for streptomycin dosing in patients with marked obesity due to decreased distribution of extracellular fluids in adipose tissues. Dosing based on actual body weight will result in supratherapeutic concentrations.[65645]

    Geriatric

    Vestibular dysfunction resulting from the parenteral administration of streptomycin is cumulatively related to the total daily dose. When 1.8 to 2 g/day are given, symptoms are likely to develop in a large percentage of patients, especially in geriatric patients, within 4 weeks. Therefore, it is recommended that caloric and audiometric tests be done before, during, and after intensive therapy with streptomycin to facilitate detection of any vestibular dysfunction and/or impairment of hearing which may occur.[30007] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of parenteral aminoglycosides must be accompanied by monitoring of renal function tests, including a baseline value, and serum drug concentrations, with the exception of single-dose prophylactic administration. Serious consequences may occur insidiously if adequate monitoring does not occur; the drug may cause or worsen hearing loss and renal failure. Use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.[60742]

    Pregnancy

    Streptomycin can cause fetal harm when administered to a pregnant woman. Because streptomycin readily crosses the placental barrier, caution in use of the drug is important to prevent ototoxicity in the fetus. If streptomycin is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to the fetus.

    Breast-feeding

    Because of the potential for serious adverse reactions in nursing infants from streptomycin, consider discontinuing breast-feeding or streptomycin, taking into account the importance of the drug to the mother.[30007] However, previous American Academy of Pediatrics recommendations considered streptomycin to be usually compatible with breast-feeding.[27500] Aminoglycosides are generally excreted into breast milk in low concentrations. They are poorly absorbed from the gastrointestinal tract and are not likely to cause adverse events in nursing infants.[47299] Streptomycin breast milk concentrations range from 0.3 to 0.6 mcg/mL with a milk:plasma ratio of 0.12 to 1.[47299] Streptomycin can be used during breast-feeding.

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / 0-1.0
    arachnoiditis / Early / Incidence not known
    hearing loss / Delayed / Incidence not known
    ototoxicity / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    nephrotoxicity / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known

    Moderate

    encephalopathy / Delayed / Incidence not known
    neurotoxicity / Early / Incidence not known
    neuritis / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    amblyopia / Delayed / Incidence not known
    vitamin B12 deficiency / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known

    Mild

    weakness / Early / 1.0-10.0
    tinnitus / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    fever / Early / Incidence not known
    rash / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known
    paresthesias / Delayed / Incidence not known
    vitamin B6 deficiency / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acyclovir: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
    Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
    Aminosalicylate sodium, Aminosalicylic acid: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides such as streptomycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B lipid complex (ABLC): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides such as streptomycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B liposomal (LAmB): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides such as streptomycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides such as streptomycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as the aminoglycosides, as the risk of renal impairment may be increased.
    Aspirin, ASA: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Dipyridamole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Omeprazole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Oxycodone: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Pravastatin: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Urinary concentrations of streptomycin could interfere with the therapeutic effectiveness of BCG. Postpone instillation of BCG if the patient is receiving antibiotics.
    Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as aminoglycosides (particularly kanamycin, streptomycin, and neomycin).Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, with aminoglycosides may have additive nephrotoxic potential.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Beractant: (Moderate) A reduced activity of streptomycin may occur in the presence of surfactant when given via nebulization.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Bismuth Subsalicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bleomycin: (Moderate) Previous treatment with nephrotoxic agents, like aminoglycosides, may result in decreased clearance of bleomycin if renal function has been impaired.
    Botulinum Toxins: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
    Bumetanide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Calfactant: (Moderate) A reduced activity of streptomycin may occur in the presence of surfactant when given via nebulization.
    Capreomycin: (Major) The concomitant use of capreomycin and aminoglycosides may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration of capreomycin with other potentially nephrotoxic drugs, including aminoglycosides may increase serum concentrations of either capreomycin or aminoglycosides. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Aminoglycosides have also been reported to interfere with nerve transmission at the neuromuscular junction. Concomitant administration of capreomycin with aminoglycosides should be avoided if possible; however, if they must be coadministered, use extreme caution.
    Carbetapentane; Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carboplatin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely.
    Cefepime: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotetan: (Minor) Cefotetan's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefoxitin: (Minor) Cefoxitin's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefprozil: (Minor) Cefprozil's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime; Avibactam: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftizoxime: (Minor) Ceftizoxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefuroxime: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Codeine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpromazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Choline Salicylate; Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Cidofovir: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Cisplatin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
    Clindamycin: (Moderate) Concomitant use of aminoglycosides and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Clofarabine: (Major) Avoid the concurrent and/or sequential use of streptomycin and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity.
    Codeine; Phenylephrine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Codeine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Colfosceril; Cetyl Alcohol; Tyloxapol: (Moderate) A reduced activity of streptomycin may occur in the presence of surfactant when given via nebulization.
    Colistin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Cyclizine: (Minor) Cyclizine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Cyclosporine: (Major) Cyclosporine should be used cautiously with nephrotoxic drugs, as cyclosporine itself can cause structural kidney damage. Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as streptomycin. Monitor renal function and fluid status carefully during cyclosporine usage.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Deferasirox: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Dimenhydrinate: (Minor) Dimenhydrinate and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity, including nausea secondary to vertigo.
    Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Ibuprofen: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Naproxen: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Enflurane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Entecavir: (Moderate) Because entecavir is primarily eliminated by the kidneys and aminoglycosides can affect renal function, concurrent administration with aminoglycosides may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Ethacrynic Acid: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Ethiodized Oil: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Etomidate: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Fluphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by aminoglycosides.
    Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as aminoglycosides.
    Fospropofol: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Furosemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Gallium Ga 68 Dotatate: (Major) Avoid concomitant use of mannitol and aminoglycosides, if possible. Concomitant administration of systemic therapy may increase the risk of ototoxicity and nephrotoxicity. In addition, systemic mannitol may alter the serum and tissue concentrations of aminoglycosides and increase the risk for aminoglycoside toxicity. If use together is necessary, monitor renal function and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates). Studies to evaluate a potential interaction between inhaled formulations of mannitol and tobramycin have not been conducted.
    Gallium: (Contraindicated) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as aminoglycosides, may increase the risk for developing severe renal insufficiency. If use of an aminoglycoside is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of the aminoglycoside is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    Ganciclovir: (Major) Concurrent use of nephrotoxic agents, such as the aminoglycosides, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
    General anesthetics: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Ginger, Zingiber officinale: (Minor) Ginger may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Gold: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
    Halothane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Ibandronate: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Ibuprofen lysine: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Immune Globulin IV, IVIG, IGIV: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and aminoglycosides due to the risk of glomerulonephritis and nephrotoxicity.
    Iodixanol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iohexol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopamidol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopromide: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Ioversol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Isoflurane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Isosulfan Blue: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Ketamine: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Mannitol: (Major) Avoid concomitant use of mannitol and aminoglycosides, if possible. Concomitant administration of systemic therapy may increase the risk of ototoxicity and nephrotoxicity. In addition, systemic mannitol may alter the serum and tissue concentrations of aminoglycosides and increase the risk for aminoglycoside toxicity. If use together is necessary, monitor renal function and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates). Studies to evaluate a potential interaction between inhaled formulations of mannitol and tobramycin have not been conducted.
    Meclizine: (Minor) Meclizine and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo).
    Meperidine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Mesoridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Methohexital: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Non-Ionic Contrast Media: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Nonsteroidal antiinflammatory drugs: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as streptomycin.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Pamidronate: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Pentamidine: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Perphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Perphenazine; Amitriptyline: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Polymyxin B: (Major) The concomitant use of systemic Polymyxin B with systemic aminoglycosides increases the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Poractant Alfa: (Moderate) A reduced activity of streptomycin may occur in the presence of surfactant when given via nebulization.
    Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Promethazine; Dextromethorphan: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Promethazine; Phenylephrine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Propofol: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Pyridostigmine: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Salicylates: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Salsalate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Sevoflurane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Streptozocin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
    Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Surfactants: (Moderate) A reduced activity of streptomycin may occur in the presence of surfactant when given via nebulization.
    Tacrolimus: (Moderate) Additive nephrotoxicity is possible if aminoglycosides are used with tacrolimus. Care should be taken in using tacrolimus with other nephrotoxic drugs. Assessment of renal function in patients who have received tacrolimus is recommended, as the tacrolimus dosage may need to be reduced
    Telavancin: (Major) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs (e.g., systemic aminoglycosides) may lead to additive nephrotoxicity. Televancin is closely related to vancomycin. In one clinical study, vancomycin coadministration, high aminoglycoside trough levels, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Closely monitor renal function and adjust telavancin doses based on creatinine clearance/renal function, and aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Tenofovir Alafenamide: (Moderate) Tenofovir-containing products, should be avoided with concurrent or recent use of a nephrotoxic agent, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir, and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
    Tenofovir, PMPA: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Thiopental: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Thioridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Torsemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Trifluoperazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Trimethobenzamide: (Minor) Because of trimethobenzamide's antiemetic pharmacology, the drug may effectively mask dizziness, tinnitus, or vertigo that are associated with ototoxicity induced by various medications, including the aminoglycosides. Clinicians should be aware of this potential interaction and take it into consideration when monitoring for aminoglycoside-induced side effects.
    Tubocurarine: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Urea: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including urea. In addition, urea may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Valacyclovir: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with valacyclovir. Carefully monitor renal function during concomitant therapy.
    Valganciclovir: (Major) Concurrent use of nephrotoxic agents, such as aminoglycosides, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Vancomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Vitamin C: (Moderate) Monitor for decreased efficacy of streptomycin during coadministration; discontinue ascorbic acid therapy if decreased efficacy is suspected. Coadministration may result in decreased efficacy of streptomycin.
    Voclosporin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aminoglycosides, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
    Zalcitabine, ddC: (Moderate) Drugs such as parenteral aminoglycosides may increase the risk of developing peripheral neuropathy or other zalcitabine-associated adverse events by interfering with the renal clearance of zalcitabine and thereby raising systemic drug exposure. Coadministration of these drugs with zalcitabine requires frequent clinical and laboratory monitoring, with dosage adjustment for any significant change in renal function.
    Zoledronic Acid: (Moderate) Since zoledronic acid is eliminated by the kidney, coadministration of zoledronic acid with other potentially nephrotoxic drugs may increase serum concentrations of either zoledronic acid and/or these coadministered drugs. Theoretically, the chronic coadministration of zoledronic acid with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity.

    PREGNANCY AND LACTATION

    Pregnancy

    Streptomycin can cause fetal harm when administered to a pregnant woman. Because streptomycin readily crosses the placental barrier, caution in use of the drug is important to prevent ototoxicity in the fetus. If streptomycin is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to the fetus.

    Because of the potential for serious adverse reactions in nursing infants from streptomycin, consider discontinuing breast-feeding or streptomycin, taking into account the importance of the drug to the mother.[30007] However, previous American Academy of Pediatrics recommendations considered streptomycin to be usually compatible with breast-feeding.[27500] Aminoglycosides are generally excreted into breast milk in low concentrations. They are poorly absorbed from the gastrointestinal tract and are not likely to cause adverse events in nursing infants.[47299] Streptomycin breast milk concentrations range from 0.3 to 0.6 mcg/mL with a milk:plasma ratio of 0.12 to 1.[47299] Streptomycin can be used during breast-feeding.

    MECHANISM OF ACTION

    Streptomycin is bactericidal in action. Similar to other aminoglycosides, it works by inhibiting bacterial protein synthesis through irreversible binding to the 30 S ribosomal subunit of susceptible bacteria. Streptomycin is actively transported into the bacterial cell where it binds to receptors present on the 30 S ribosomal subunit. This binding interferes with messenger RNA (mRNA) and the subunit. As a result, abnormal, nonfunctional proteins are formed due to misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins. One aspect essential to aminoglycoside lethality is the need to achieve intracellular concentrations in excess of extracellular. Anaerobic bacteria are not susceptible to aminoglycosides due, at least in part, to a lack of an active transport mechanism for aminoglycoside uptake.
     
    Against gram-negative aerobic rods, aminoglycosides exhibit 'concentration-dependent killing' and a 'post-antibiotic effect' (PAE). 'Concentration-dependent killing' describes the principle that bactericidal effects increase as the concentration increases. PAE is where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. The post-antibiotic effect can be bacteria specific, as well as drug specific. The PAE of aminoglycosides is short for most gram-positive organisms (< 2 hours) and longer for gram-negative organisms (2—8 hours), such as E. coli, K. pneumoniae, and P. aeruginosa. Both of these phenomena are being exploited in designing dosage regimens that employ higher doses administered at longer intervals. The major pharmacodynamic parameter that determines efficacy of aminoglycosides is the serum peak concentration to MIC ratio (peak:MIC). Both time-kill studies as well as studies in humans have shown that a peak:MIC of >8—12:1 is associated with successful regimens.
     
    The mechanism of renal toxicity with aminoglycosides is associated with accumulation of aminoglycosides in the renal tubule, which is a saturable process. Elevated serum trough concentrations are associated with an increased risk of toxicity (see Adverse Reactions).
     
    Aminoglycoside resistance is well documented. There are a variety of resistance mechanisms employed by different pathogens. Enzymatic inhibition by gram-negative pathogens and Enterococcus sp. via aminoglycoside-modifying enzymes is achieved by modification of the aminoglycoside as it is transported across the cytoplasmic membrane. Alterations in the inner membrane porin channels by Pseudomonas aeruginosa decrease antimicrobial penetration to the site of activity within the bacterial cell. Some gram-negative organisms and Enterococcus sp. can alter the ribosomal target sites of the aminoglycosides to decrease binding, thereby decreasing antimicrobial activity.

    PHARMACOKINETICS

    Streptomycin can be administered intramuscularly or intravenously. Streptomycin distributes into extracellular fluid; therefore, peak serum concentrations may be lower in patients with a large volume of extracellular fluid. Generally, the volume of distribution is low (approximately 0.3 L/kg). The volume of distribution may be higher in patients with sepsis, fever, severe burns, congestive cardiac failure, and peritonitis, which may result in lower peak concentrations. Protein binding of streptomycin is negligible. After administration, streptomycin can be detected in sputum, peritoneal fluid, synovial fluid, and abscess fluid. Significant amounts have been found in the pleural fluid and tuberculous cavities. Streptomycin passes through the placenta with serum concentrations in the cord blood similar to maternal concentrations. Small amounts are excreted in milk, saliva, and sweat. Streptomycin appears in low concentrations in the CSF and ocular tissues.
     
    Streptomycin is not metabolized. Streptomycin is excreted by glomerular filtration; therefore, elimination half-life varies according to renal function. Febrile states may be associated with decreased serum concentrations and a shorter half-life. In severely burned patients, the half-life may also be decreased. In adults with normal renal function, the plasma elimination half-life of streptomycin is approximately 2 to 3 hours; however, there is considerable interpatient variation. Clearance is generally more rapid in pediatric patients. In adults with normal renal function, 29% to 89% of a single IM dose of the drug is excreted unaltered in urine within 24 hours.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Intravenous Route

    In a small pharmacokinetic study comparing intravenous (n = 19) and intramuscular (n = 11) streptomycin regimens, equivalent doses of intravenous streptomycin produced modestly higher median Cmax concentrations (43.6 mcg/mL) than intramuscular doses (42.6 mcg/mL). As intravenous doses were increased, proportional increases in Cmax (p = 0.032) and AUC (p = 0.001) were seen. Linear kinetics was noted.

    Intramuscular Route

    Intramuscular absorption of streptomycin is variable. After a single intramuscular 1 g dose, peak streptomycin concentrations of about 25 to 50 mcg/mL are reached within 1 hour and diminish to about 50% after 5 to 6 hours. In neonates, peak plasma streptomycin concentrations of 29 mcg/mL occur within 2 hours after a single IM dose.