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Tobrex
Classes
Aminoglycoside Antibiotics
Ophthalmological Anti-infectives
Respiratory Aminoglycoside Antibiotics
Administration
For storage information, see specific product information within the How Supplied section.
Injectable AdministrationVisually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous (IV) Infusion
1.2 g Bulk Powder Vials for Injection
Reconstitution
Reconstitute the vial with 30 mL of Sterile Water for Injection to provide a solution containing 40 mg/mL.
The bulk vial should be penetrated 1 time with a suitable sterile dispensing set that allows measured distribution of the contents. The entire contents of the bulk vial should be used during reconstitution.
Once penetration of the bulk vial has occurred, the contents should be used within 24 hours.
FURTHER DILUTION IS REQUIRED.
Storage: Reconstituted vials are stable under refrigeration (20 to 25 degrees C or 68 to 77 degrees F) for 96 hours or at room temperature for 24 hours.[34037]
Dilution
Dilute in an appropriate volume corresponding with the dose in an appropriate solution. Final volume for administration depends on the patient's size and fluid status; the final volume must be sufficient to allow for accurate drug administration. Volumes as small as 25 mL have been used.[34198]
A dilution concentration of 5 mg/mL has been suggested.[40036] For neonates, a dilution of 2 mg/mL has been recommended.[53249]
Larger doses are commonly diluted in 50 to 100 mL.[34037]
Solution for Injection Vials
Dilution
Dilute in an appropriate volume corresponding with the dose in an appropriate solution. Final volume for administration depends on the patient's size and fluid status; the final volume must be sufficient to allow for accurate drug administration. Volumes as small as 25 mL have been used.[34198]
A dilution concentration of 5 mg/mL has been suggested.[40036] For neonates, a dilution of 2 mg/mL has been recommended.[53249]
Larger doses are commonly diluted in 50 to 100 mL.[54179]
Solution for Injection Bulk Vials
Dilution
The bulk vial should be penetrated 1 time with a suitable sterile dispensing set that allows measured distribution of the contents.
The entire contents of the bulk vial should be used during reconstitution. Any unused portion must be discarded within 4 hours.[54180]
Dilute in an appropriate volume corresponding with the dose in an appropriate solution. Final volume for administration depends on the patient's size and fluid status; the final volume must be sufficient to allow for accurate drug administration. Volumes as small as 25 mL have been used.[34198]
A dilution concentration of 5 mg/mL has been suggested.[40036] For neonates, a dilution of 2 mg/mL has been recommended.[53249]
Larger doses are commonly diluted in 50 to 100 mL.[54180]
Premixed IV Solution
Preparation
Check for leaks by squeezing bag firmly. Do not add supplementary medication.
Adjustments may be made to premixed containers to either add or remove contents to provide an appropriate dose.
Do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.[49699]
Intermittent IV Infusion
Infuse over 20 to 60 minutes.[34037] An infusion time of 15 minutes has been recommended in neonates.[53249]
Intravenous (IV) Push†
NOTE: Tobramycin is not FDA-approved for IV Push administration.
Reconstitution / Dilution
A report included 3652 doses of tobramycin administered by IV push in an outpatient parenteral antibiotic (OPAT) setting.
Doses less than 800 mg were diluted in 0.9% Sodium Chloride Injection to a total volume of 20 mL.
Doses 800 mg or larger were administered undiluted as the 40 mg/mL solution as supplied by the manufacturer.
A study included 5 adults who received tobramycin via IV push.
Doses of 2 mg/kg were prepared in 10 mL of 5% Dextrose Injection.
Doses injected within 2 to 3 minutes of preparation.
Stability: Plastic syringes reconstituted with Sterile Water for Injection from 1.2 g vials to a concentration of 40 mg/mL showed no significant change in concentrations after 2 months at 4 to 25 degrees C.
Intermittent IV Push
The most common IV push rate is 3 to 5 minutes; however, a range of 15 seconds to 5 minutes has been reported.
Do not use solutions prepared from commercially available bulk packages and premixed solution for IM administration.[49699] [54180]
Withdraw appropriate dose directly from the vial of solution for injection. No dilution necessary. Inject deeply into a large muscle mass.[54179]
In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.[53249]
Nebulized Solution for Inhalation
The solution for nebulization is administered by inhalation only. Do not administer subcutaneously, intravenously, or intrathecally.
Visually inspect the solution before use. The solution should be clear and without particles. The solution may darken with age; this color change does not mean there is any change in the quality of the medicine. Do not use if the solution is cloudy or has particles.
Wash hands with soap and water before preparing each dose.
Squeeze all the medicine from the ampule into the nebulizer cup, and firmly secure the nebulizer top. Do not dilute or mix with other medicines in the nebulizer.
Turn on the compressor and check for a steady mist to be released from the mouthpiece. If there is no mist, check all tubing connections and make sure the compressor is working properly.[47300] [52050] [58565]
If a patient misses a dose, administer the dose as soon as possible anytime up to 6 hours before the next scheduled dose. If less than 6 hours remain before the next dose, wait until the next scheduled dose.[52050]
Administration of Nebulized Solution for Inhalation
Administer via inhalation while the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help the patient breathe through the mouth. Do not block the airflow with the tongue.
Deliver the dose by inhalation over approximately 15 minutes, using a recommended hand-held nebulizer. Full treatment dose has been administered when the mouthpiece makes a spitting noise for at least 1 minute and the nebulizer cup is empty.
If treatment is interrupted (i.e., need to cough or rest during treatment), turn off the compressor to save the medicine. Turn the compressor back on when ready to restart the treatment.[47300] [52050] [58565]
Powder for Inhalation
Capsules are to be used with a Podhaler device and the contents of the capsules are for oral inhalation only. Do not swallow the capsules.
Do not use the Podhaler capsules with any other device. Do not use the Podhaler to take any other medications
Each Podhaler device is used for only 7 days. After 7 days, discard the used Podhaler device and its storage case. A new Podhaler device will be supplied for use with each weekly pack of capsules.
A reserve Podhaler device is provided and should be used if the original device is wet, dirty, broken, has been dropped, or does not seem to be piercing the capsules properly.
Administer after other inhaled medications and/or chest physiotherapy.
Doses should be administered as close to 12 hours apart as possible and not less than 6 hours apart.
Small pieces of the capsules can get into the mouth; it is ok to swallow or inhale them.
Storage: Store capsules in the blister cards until immediately before administration.[53821]
Administration of Powder for Inhalation
Thoroughly wash and dry hands.
Hold the base of the Podhaler device and unscrew lid counter-clockwise. Stand the device upright.
Unscrew the mouthpiece in a counter-clockwise direction while holding the body of the Podhaler.
Tear the blister card in half lengthwise along the precut lines.
Peel back the foil covering the first capsule. Only unfoil and remove 1 capsule at a time, immediately before use.
Place 1 capsule in the capsule chamber at the top of the Podhaler device. Do not insert directly into the top of the mouthpiece.
Reattach the mouthpiece and tighten in a clockwise direction; do not overtighten.
While holding the Podhaler device with mouthpiece pointed downwards, press the blue button all the way down with your thumb. Release the blue button; do not press more than once.
With mouth away from the mouthpiece, exhale completely.
Place mouth over the mouthpiece, close lips tightly, and inhale deeply with a single breath. Hold breath for about 5 seconds, then exhale normally away from the Podhaler device.
After a few normal breaths away from the device, repeat the exhale and inhale process using the same capsule.
After the second inhalation from the Podhaler device, unscrew the mouthpiece and remove the capsule from the capsule chamber.
Inspect the used capsule. It should be pierced and empty; if so, throw the capsule away. If the capsule is pierced but more than just a fine coating of powder remains, put the capsule back into the capsule chamber with pierced side pointed down. Reattach the mouthpiece and repeat the exhale and inhale process. If the capsule is not pierced, reinsert into the capsule chamber, reattach the mouthpiece, and repeat the exhale and inhale process. If the capsule is still not pierced, use the reserve Podhaler device.
Once the contents of the first capsule have been successfully inhaled, repeat the process 3 more times until the total dose of 4 capsules has been inhaled.
Once the full dose has been administered, reattach the mouthpiece onto the Podhaler device and wipe with a clean, dry cloth. Throw away all empty capsules; do not store capsules in the Podhaler device.
Do not wash the Podhaler with water; it needs to stay dry at all times.[53821]
Ointment or Solution
Instruct patient on proper instillation of eye ointment and/or solution.
Do not to touch the tip of the dropper to the eye, fingertips, or other surface.
Adverse Reactions
bronchospasm / Rapid / 0.5-5.0
nephrotoxicity / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
hyposthenuria / Delayed / Incidence not known
renal tubular acidosis (RTA) / Delayed / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
ototoxicity / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
seizures / Delayed / Incidence not known
aphonia / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
dyspnea / Early / 12.4-33.7
chest pain (unspecified) / Early / 4.5-26.0
hemoptysis / Delayed / 12.4-19.4
dysphonia / Delayed / 3.8-13.6
wheezing / Rapid / 5.0-6.8
eosinophilia / Delayed / 2.0-2.0
pyuria / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
neurotoxicity / Early / Incidence not known
bullous rash / Early / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
confusion / Early / Incidence not known
hypokalemia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
vitamin B12 deficiency / Delayed / Incidence not known
cough / Delayed / 10.0-46.1
pharyngitis / Delayed / 38.0-38.0
asthenia / Delayed / 35.7-35.7
rhinitis / Early / 34.5-34.5
fever / Early / 12.4-32.9
headache / Early / 11.4-26.7
anorexia / Delayed / 18.6-18.6
vomiting / Early / 5.7-14.0
abdominal pain / Early / 12.8-12.8
nausea / Early / 7.5-11.2
weight loss / Delayed / 10.1-10.1
sinusitis / Delayed / 8.1-8.1
nasal congestion / Early / 7.2-8.1
otalgia / Early / 7.4-7.4
back pain / Delayed / 7.0-7.0
epistaxis / Delayed / 1.9-7.0
dysgeusia / Early / 0.5-6.6
diarrhea / Early / 1.9-6.2
malaise / Early / 6.2-6.2
dizziness / Early / 5.8-5.8
rash / Early / 2.3-5.4
hyperventilation / Early / 5.4-5.4
myalgia / Early / 4.7-4.7
throat irritation / Early / 1.9-4.5
laryngitis / Delayed / 4.3-4.3
tinnitus / Delayed / 3.0-3.0
cylindruria / Delayed / Incidence not known
vertigo / Early / Incidence not known
weakness / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
leukocytosis / Delayed / Incidence not known
lethargy / Early / Incidence not known
vitamin B6 deficiency / Delayed / Incidence not known
Boxed Warning
Monitor patients receiving systemic aminoglycosides, such as tobramycin, closely for nephrotoxicity. Aminoglycosides are associated with major toxic effects on the renal tubules. In patients with preexisting renal impairment, renal failure, or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe nephrotoxic adverse reactions are sharply increased. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine). When monitoring tobramycin serum concentrations using conventional dose regimens, avoid prolonged peak concentrations above 12 mcg/mL and trough concentrations above 2 mcg/mL. Single-daily dosing regimens that produce higher peak serum concentrations have been used without additional toxicity noted; however, it is important to allow the trough concentration to decrease appropriately before redosing. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in tobramycin removal in the event of overdose or toxic reactions, especially if renal function is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and/or sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic and/or neurotoxic because toxicity may be additive. Patients of advanced age and patients with dehydration or diabetes mellitus are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.
Monitor patients receiving systemic and inhaled aminoglycosides, such as tobramycin, for neurotoxicity, including ototoxicity and hearing impairment. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. Consider serial audiograms for high-risk patients. The risk of hearing loss increases with the degree of exposure (high or prolonged therapy), pre-existing renal impairment, concomitant or sequential nephrotoxic or ototoxic agents, dehydration, and advanced age. Patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly the m.1555A>G variant, may develop ototoxicity even when aminoglycoside serum concentrations are within the recommended range. These variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity, including severe cases, is unknown. If there is a known maternal history of ototoxicity due to aminoglycosides or a known mitochondrial DNA variant, consider alternative treatments unless the severity of the infection and lack of alternatives outweighs the risk of permanent hearing loss. Discontinue therapy if there is evidence of auditory or vestibular toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. When monitoring tobramycin serum concentrations during use of conventional dose regimens, avoid prolonged tobramycin peak concentrations above 12 mcg/mL and trough concentrations above 2 mcg/mL. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Auditory changes are irreversible, usually bilateral, and may be partial or total. Symptoms of ototoxicity can include dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss and may manifest during therapy or after discontinuation. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions.
Systemic exposure to tobramycin may cause fetal harm during pregnancy. Aminoglycosides cross the placenta. There have been reports of total irreversible bilateral congenital deafness in newborns whose mothers received streptomycin, a related aminoglycoside, during pregnancy. Serious side effects to the mother, fetus, or newborn have not been reported with use of other aminoglycosides when used during pregnancy. If tobramycin injection is used during pregnancy or if the patient becomes pregnant during treatment with tobramycin, advise the mother of the potential risk to the fetus.[34037] [54179] Although there are no available data on inhaled tobramycin use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, systemic absorption of tobramycin after inhaled administration is expected to be minimal. There are risks to the mother associated with cystic fibrosis in pregnancy, including preterm delivery.[47300] [53821] [58565] Reproduction studies in animals at doses up to 33 times the normal human systemic dose have revealed no evidence of impaired fertility or harm to the fetus due to ophthalmic tobramycin use. Because animal studies are not always predictive of human response, use ophthalmic tobramycin during pregnancy only if clearly needed.[52361] [52362]
Use tobramycin with caution in neonates and premature neonates due to renal immaturity and the prolongation of serum half-life of the drug, which increases the risk of aminoglycoside-induced toxicity. When tobramycin is used in the neonatal population, careful monitoring is warranted for signs and symptoms of toxicity including auditory, vestibular, and renal toxicity and neuromuscular blockade.
Common Brand Names
AK-Tob, BETHKIS, Kitabis Pak, Nebcin, Tobi, TOBI Podhaler, Tobrasol, Tobrex
Dea Class
Rx
Description
Parenteral, inhaled, or ophthalmic aminoglycoside antibiotic
Most active against aerobic gram-negative rods
Risk of ototoxicity and renal toxicity with high serum concentration
Dosage And Indications
300 mg inhaled by nebulizer twice daily for 28 days in alternating 28-day periods. Tobramycin inhalation solution is FDA-approved for persons with FEV1 of 25% to 75% predicted for TOBI or FEV1 of 40% to 80% predicted for Bethkis.
300 mg inhaled by nebulizer twice daily for 28 days in alternating 28-day periods. Tobramycin inhalation solution is FDA-approved for persons with FEV1 of 25% to 75% predicted for TOBI or FEV1 of 40% to 80% predicted for Bethkis.
112 mg inhaled by mouth twice daily for 28 days in alternating 28-day periods. Tobramycin inhalation powder is FDA-approved for persons with FEV1 of 25% to 80% predicted.
112 mg inhaled by mouth twice daily for 28 days in alternating 28-day periods. Tobramycin inhalation powder is FDA-approved for persons with FEV1 of 25% to 80% predicted.
10 mg/kg/dose IV every 24 hours. Doses as high as 12 to 15 mg/kg/dose IV every 24 hours have been used. The FDA-approved dosage is 10 mg/kg/day IV or IM in 4 divided doses.
10 mg/kg/dose IV every 24 hours. Doses as high as 12 to 15 mg/kg/dose IV every 24 hours have been used. The FDA-approved dosage is 10 mg/kg/day IV or IM in 4 divided doses.
300 mg inhaled by nebulizer twice daily for 28 days.
300 mg inhaled by nebulizer twice daily for 28 days.
112 mg inhaled by mouth twice daily for 28 days.
112 mg inhaled by mouth twice daily for 28 days.
NOTE: Use lean body mass to calculate the tobramycin dose. Adjust dose based on serum tobramycin concentrations.
For the treatment of nonspecific LRTIs. Intravenous or Intramuscular dosage (extended-interval dosing)† Adults
5 to 7 mg/kg/dose IV or IM every 24 hours.[34172] [34173] [34175] [34186]
5 to 7.5 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 24 hours.
4 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 48 hours.
3 mg/kg/day IV or IM divided every 8 hours; doses up to 5 mg/kg/day IV or IM divided every 6 to 8 hours may be required in life-threatening infections.[54179]
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 18 hours.[51918] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. This dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 24 hours.[51918] [53249] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. This dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 24 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours. This dosing does not account for gestational age or birthweight.
5 to 7 mg/kg/dose IV every 24 hours for 7 days as part of combination therapy.[34172] [34173] [34175] [34186] [61215]
3 mg/kg/day IV divided every 8 hours for 5 to 7 days as an alternative as part of combination therapy. Doses up to 5 mg/kg/day IV divided every 6 to 8 hours may be required in life-threatening infections. [54179]
6 to 7.5 mg/kg/day IV divided every 6 to 8 hours for 5 to 7 days as an alternative as part of combination therapy.
5 to 7 mg/kg/dose IV every 24 hours for 5 to 7 days as an alternative as part of combination therapy.[34172] [34173] [34175] [34186]
5 to 7.5 mg/kg/dose IV every 24 hours for 5 to 7 days as an alternative as part of combination therapy.
0.5 inch ribbon in the affected eye(s) 2 or 3 times daily; up to 0.5 inch ribbon in the affected eye(s) every 3 to 4 hours until improvement for severe infections.
0.5 inch ribbon in the affected eye(s) 2 or 3 times daily; up to 0.5 inch ribbon in the affected eye(s) every 3 to 4 hours until improvement for severe infections.
1 to 2 drops in the affected eye(s) every 4 hours; up to 2 drops in the affected eye(s) every hour until improvement for severe infections.
1 to 2 drops in the affected eye(s) every 4 hours; up to 2 drops in the affected eye(s) every hour until improvement for severe infections.
NOTE: Serum 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.
For the treatment of peritonitis in patients receiving peritoneal dialysis. Intraperitoneal dosage† Adults
8 mg/L IP loading dose then 4 mg/L IP as continuous therapy in each dialysate exchange bag. For intermittent therapy, 0.6 mg/kg IP in anuric patients and 0.75 mg/kg IP in non-anuric patients administered during the longest daily dialysate dwell period.
8 mg/L IP loading dose then 4 mg/L IP as continuous therapy in each dialysate exchange bag. For intermittent therapy, 0.6 mg/kg IP in anuric patients and 0.75 mg/kg IP in non-anuric patients administered during the longest daily dialysate dwell period.
5 to 7 mg/kg/dose IV or IM. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary. Treatment is recommended for 4 to 7 days.
5 to 7.5 mg/kg/dose IV or IM every 24 hours. Treatment is recommended for 4 to 7 days.
5 mg/kg/dose IV or IM every 24 hours.
4 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 48 hours.
3 mg/kg/day IV or IM divided every 8 hours; doses up to 5 mg/kg/day IV or IM divided every 6 to 8 hours may be required in life-threatening infections. Treatment is recommended for 4 to 7 days.
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Treatment is recommended for 4 to 7 days.
2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
NOTE: Serum 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.[54179]
Intravenous or Intramuscular dosage (extended-interval dosing)† Adults
5 to 7 mg/kg/dose IV or IM every 24 hours.[34172] [34173] [34175] [34186] Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
5 to 7.5 mg/kg/dose IV or IM every 24 hours.[51960] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]
5 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]
4 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]
5 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 48 hours.
5 mg/kg/day IV or IM divided every 6 to 8 hours is recommended for life-threatening infections.[54179] Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.[41183] [54179] Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
2.5 mg/kg/dose IV or IM every 18 hours.[51918] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 8 hours.[51918] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.[54179] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]
2.5 mg/kg/dose IV or IM every 12 hours.[51918] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.[54179] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]
2.5 mg/kg/dose IV or IM every 18 to 24 hours.[51918] [53249] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 12 hours.[51918] The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.[54179] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]
2.5 mg/kg/dose IV or IM every 18 hours.[51918] The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.[54179] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]
2.5 mg/kg/dose IV or IM every 18 to 24 hours.[51918] [53249] The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight.[54179]
NOTE: Use lean body mass to calculate the tobramycin dose. Adjust dose based on serum tobramycin concentrations.[54179]
For the treatment of osteomyelitis. Intravenous dosage (extended-interval dosing)† Adults
5 to 7 mg/kg/dose IV every 24 hours for 4 to 6 weeks.[34172] [34173] [34175] [34186]
5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
4 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 48 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
3 mg/kg/day IV divided every 8 hours for 4 to 6 weeks; doses up to 5 mg/kg/day IV divided every 6 to 8 hours may be required in life-threatening infections.
6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours.
2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours.
2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
5 to 7 mg/kg/dose IV every 24 hours.[34172] [34173] [34175] [34186] Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.
5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
5 to 7.5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
4 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 36 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
5 mg/kg/dose IV every 48 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
3 mg/kg/day IV divided every 8 hours; doses up to 5 mg/kg/day IV divided every 6 to 8 hours may be required in life-threatening infections. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.
6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
6 to 7.5 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours.
2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours.
2.5 mg/kg/dose IV every 18 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
2.5 mg/kg/dose IV every 18 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 2 mg/kg/dose IV every 12 hours; however, this dosing does not account for gestational age or birthweight.
NOTE: Serum 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.[54179]
For the treatment of unspecified skin and skin structure infections. Intravenous or Intramuscular dosage (extended-interval dosing)† Adults
5 to 7 mg/kg/dose IV or IM every 24 hours.[34172] [34173] [34175] [34186]
5 to 7.5 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 24 hours.
4 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 24 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 36 hours.
5 mg/kg/dose IV or IM every 48 hours.
3 mg/kg/day IV or IM divided every 8 hours; doses up to 5 mg/kg/day IV or IM divided every 6 to 8 hours may be required in life-threatening infections.
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 18 to 24 hours.[51918] [53249] The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 18 to 24 hours.[51918] [53249] The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight.[54179]
5 to 7 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections .[34172] [34173] [34175] [34186]
5 to 7.5 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
5 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
4 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
5 mg/kg/dose IV or IM every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
5 mg/kg/dose IV or IM every 36 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
5 mg/kg/dose IV or IM every 36 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
5 mg/kg/dose IV or IM every 48 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
5 mg/kg/day IV or IM divided every 6 to 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
2.5 mg/kg/dose IV or IM every 18 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.
2.5 mg/kg/dose IV or IM every 18 to 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.[51918] [53249] The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179]
2.5 mg/kg/dose IV or IM every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 18 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours.
2.5 mg/kg/dose IV or IM every 18 to 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.[51918] [53249] The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight.[54179]
NOTE: Serum 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.
Intravenous or Intramuscular dosage (extended-interval dosing)† Adults
5 to 7 mg/kg/dose IV or IM. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.[34172] [34173] [34175] [34186] The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.[32690]
5 to 7.5 mg/kg/dose IV or IM every 24 hours.[51960] [63245] The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.[32690]
5 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
4 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-neg
ative bacilli.Neonates 30 to 34 weeks gestation and 15 days and older
5 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
5 mg/kg/dose IV or IM every 36 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
5 mg/kg/dose IV or IM every 36 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
5 mg/kg/dose IV or IM every 48 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.
5 mg/kg/day IV or IM divided every 8 hours. The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.[32690] [54179] [61814] [63245] The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.[32690]
2.5 mg/kg/dose IV or IM every 18 hours.[51871] [51918] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179] In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.[53249] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]
2.5 mg/kg/dose IV or IM every 8 hours.[32690] [51871] [51918] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.[54179] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]
2.5 mg/kg/dose IV or IM every 8 to 12 hours.[32690] [51871] [51918] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours.[54179] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]
2.5 mg/kg/dose IV or IM every 18 to 24 hours.[51871] [51918] [53249] The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight.[54179] In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.[53249] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]
2.5 mg/kg/dose IV or IM every 12 hours.[32690] [51871] [51918] The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.[54179] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]
2.5 mg/kg/dose IV or IM every 12 to 18 hours.[51871] [51918] The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours.[54179] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]
2.5 mg/kg/dose IV or IM every 18 to 24 hours.[51871] [51918] [53249] The FDA-approved dose is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight.[54179] In general, IM administration of antibiotics in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.[53249] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]
5 to 20 mg intraventricularly once daily in combination with systemic therapy.[32960] [61814]
5 to 20 mg intraventricularly once daily in combination with systemic therapy has been recommended in general without specific pediatric qualifications.[32690] [61814] Doses of 1.5 to 5 mg intraventricularly once daily and 2.5 mg intraventricularly every 8 hours have been used in pediatric case reports.[54320] [54321] Doses should be adjusted to maintain adequate CSF concentrations depending on the susceptibility of the infecting organism.[61814]
3 to 5 mg/kg/day IV divided every 8 hours. Guidelines recommend an aminoglycoside in combination with a beta-lactam (i.e., penicillin, cephalosporin, carbapenem) for 6 weeks for endocarditis due to non-HACEK gram-negative microorganisms.
3 to 6 mg/kg/day IV divided every 8 hours in combination with appropriate antimicrobial agent is recommended by guidelines. An aminoglycoside (specific agent depends on susceptibility), in combination with a third or fourth generation cephalosporin (i.e., ceftazidime, cefotaxime, cefepime), is a preferred treatment option for endocarditis due to gram-negative microorganisms. An aminoglycoside, in combination with ampicillin, is recommended as an alternative therapy for endocarditis due to HACEK organisms. Treat for 4 weeks for HACEK endocarditis and at least 6 weeks for endocarditis due to other gram-negative microorganisms.
NOTE: Serum 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.
For the treatment of complicated UTI and pyelonephritis including infections with difficult-to-treat resistance. Intravenous or Intramuscular dosage (extended-interval dosing)† Adults
5 to 7 mg/kg/dose IV or IM every 24 hours for 7 to 14 days alone or as combination therapy. A single dose prior to oral therapy may be used in persons not requiring hospitalization.
5 to 7.5 mg/kg/dose IV or IM every 24 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
5 to 7.5 mg/kg/dose IV or IM every 24 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
5 mg/kg/dose IV or IM every 24 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
4 mg/kg/dose IV or IM every 24 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
5 mg/kg/dose IV or IM every 24 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
5 mg/kg/dose IV or IM every 36 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
5 mg/kg/dose IV or IM every 36 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
5 mg/kg/dose IV or IM every 48 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
3 mg/kg/day IV or IM divided every 8 hours; doses up to 5 mg/kg/day IV or IM divided every 6 to 8 hours may be required in life-threatening infections.
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 6 to 7.5 mg/kg/day IV or IM divided every 6 to 8 hours; however, this dosing does not account for gestational age or birthweight. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
2.5 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
2.5 mg/kg/dose IV or IM every 18 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
2.5 mg/kg/dose IV or IM every 18 to 24 hours. The FDA-approved dosage is 2 mg/kg/dose IV or IM every 12 hours; however, this dosing does not account for gestational age or birthweight. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
7 mg/kg/dose IV as a single dose.
3 to 6 mg/kg/day IV given in 3 to 4 divided doses has been studied.
2 to 2.5 mg/kg/dose IV every 8 hours. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.
6 to 9 mg/kg/dose IV every 24 hours. In a pharmacokinetic analysis of a randomized controlled trial in pediatric patients with febrile neutropenia, age-specific initial doses of 10 mg/kg/dose IV (6 months to younger than 9 years), 8 mg/kg/dose IV (9 to 11 years), and 6 mg/kg/dose IV (12 years and older) given every 24 hours were recommended to achieve target serum tobramycin concentrations. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.
5 mg/kg IV or IM as a single preoperative dose as an alternative option as part of combination therapy for penicillin-allergic patients undergoing colorectal, gastroduodenal, biliary tract, or urologic procedures. Doses should be administered within 60 minutes prior to the surgical incision. No redosing is recommended; the duration of prophylaxis should be less than 24 hours for most procedures.
2.5 mg/kg IV or IM as a single preoperative dose as an alternative option as part of combination therapy for penicillin-allergic patients undergoing colorectal, gastroduodenal, biliary tract, or urologic procedures. Doses should be administered within 60 minutes prior to the surgical incision. No redosing is recommended; the duration of prophylaxis should be less than 24 hours for most procedures.
5 to 7 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.
4.5 to 7.5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
4 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
5 to 7 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.
4.5 to 7.5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
4 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
300 mg inhaled by nebulizer every 12 hours based on limited data.
300 mg inhaled by nebulizer every 12 hours based on limited data.
5 to 7 mg/kg/dose IV every 24 hours for 14 days as part of combination therapy.
5 to 7.5 mg/kg/dose IV every 24 hours for 14 days as part of combination therapy.
5 to 7 mg/kg/dose IV every 24 hours for a total duration of 14 days as part of combination therapy, followed by inhaled antibiotics for 4 to 12 weeks.
5 to 7.5 mg/kg/dose IV every 24 hours for 14 days as part of combination therapy, followed by inhaled antibiotics for 4 to 12 weeks.
300 mg inhaled by nebulizer every 12 hours; may be used in combination with initial systemic therapy for 14 days; treat for 4 to 12 weeks following systemic therapy.
300 mg inhaled by nebulizer every 12 hours; may be used in combination with initial systemic therapy for 14 days; treat for 4 to 12 weeks following systemic therapy.
†Indicates off-label use
Dosing Considerations
Tobramycin does not undergo hepatic metabolism. Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal ImpairmentConventional dosing:
The manufacturer recommends either maintaining the standard dose and increasing the interval between doses or decreasing the dose while maintaining an every 8 hour dosing interval. To increase the dosing interval, the manufacturer recommends multiplying the patient's serum creatinine (mg/100 mL) by 6 to determine the dosing interval (i.e., serum creatinine of 2 mg/100 mL would yield a dosing interval of 12 hours). To decrease the dose, the manufacturer recommends dividing the patient's standard dose by the serum creatinine (mg/100 mL) to determine the lower recommended dose. For example, if a patient was receiving a standard dose of 60 mg IV every 8 hours and had a serum creatinine of 2 mg/100 mL, the dose would be adjusted to 30 mg IV every 8 hours. The manufacturer does suggest measuring serum concentrations and adjusting the dose accordingly. Additionally, the status of the renal function may change throughout the course of therapy. Several dosing regimens and nomograms designed to maintain traditional serum concentrations have been published in the literature for dosing in patients with renal impairment. However, these predictive dosage regimens and nomograms may result in serum concentrations outside the targeted range; therefore, doses should be adjusted based on patient-specific serum concentrations. Factors such as site of infection and organism susceptibility may alter the goals of therapy; thereby altering dosing in patients with renal impairment. The initial dosing interval should be individualized based on specific patient and disease-state characteristics, serum concentrations goals, site of infection, organism susceptibility, weight, age, and degree and stability of renal impairment (acute versus chronic). Further dosing should be guided by serum concentrations.
Interval adjustment of extended-interval dosing of 5 or 7 mg/kg†:
CrCl 60 mL/min or more: No dosage adjustment is needed. Adjust doses based on serum concentrations and organism MIC.
CrCl 40 to 59 mL/min: 5 or 7 mg/kg IV every 36 hours. Adjust doses based on serum concentrations and organism MIC.
CrCl 20 to 39 mL/min: 5 or 7 mg/kg IV every 48 hours. Adjust doses based on serum concentrations and organism MIC.
CrCl less than 20 mL/min: 5 or 7 mg/kg IV once, then follow serial levels to determine time of next dose (serum concentration less than 1 mcg/mL). Adjust doses based on serum concentrations and organism MIC.
Dose adjustment of extended dosing of 5 mg/kg†:
CrCl 80 mL/min or more: No dosage adjustment is needed. Adjust doses based on serum concentrations and organism MIC.
CrCl 60 to 79 mL/min: 4 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
CrCl 50 mL/min: 3.5 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
CrCl 40 mL/min: 2.5 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
CrCl less than 30 mL/min: Use traditional dosing. Adjust doses based on serum concentrations and organism MIC.
Intermittent hemodialysis
For adult patients, administer half of the full dose after hemodialysis. For pediatric patients, give 2 mg/kg IV/IM after the initial hemodialysis session. Factors such as patient size, site of infection, and organism susceptibility should also be considered. Subsequent doses should be guided by serum tobramycin concentrations and organism MIC.
Peritoneal dialysis
Give 1.5 to 2 mg/kg/dose IV/IM as indicated by serum concentrations.
Continuous renal replacement therapy (CRRT)
For adult patients, administer the full dose every 24 to 48 hours as guided by serum tobramycin concentrations. For pediatric patients, give 2 to 2.5 mg/kg dose IV/IM every 12 to 24 hours as guided by serum tobramycin concentrations.
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; Aspirin: (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; Aspirin; 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. (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; 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.
Amobarbital: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
Amphotericin B lipid complex (ABLC): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tobramycin. 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 tobramycin. 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 tobramycin. 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; 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; 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.
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.
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.
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).
Butalbital; Aspirin; 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.
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.
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.
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; 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; 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 tobramycin (IV injection and inhalation solution) and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity. If the use of tobramycin inhalation solution and clofarabine is required, monitor tobramycin serum concentrations and renal function.
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.
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) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as aminoglycosides.
Daptomycin: (Moderate) The pharmacokinetics of daptomycin and tobramycin may be altered when the two antibiotics are coadministered. The serum concentration of daptomycin may be increased and the serum concentration of tobramycin may be decreased. The manufacturer recommends caution when daptomycin is coadministered with tobramycin.
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; 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.
Efavirenz; 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.
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.
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.
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.
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).
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 tobramycin.
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.
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.
Iomeprol: (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.
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.
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.
Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
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).
Methenamine; Sodium 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.
Methohexital: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
Methotrexate: (Major) Avoid concomitant use of methotrexate with tobramycin due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Tobramycin and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with tobramycin may result in decreased renal function as well as increased methotrexate plasma concentrations.
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.
Mycophenolate: (Minor) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Tobramycin may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption.
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 tobramycin.
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.
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.
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.
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.
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: (Major) Some surfactant anti infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant.
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) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, 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 a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
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.
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.
Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis).
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.
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.
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
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.
How Supplied
AK-Tob/Tobramycin/Tobrasol/Tobrex Ophthalmic Sol: 0.3%
BETHKIS/Kitabis Pak/Tobi/Tobramycin/Tobramycin Sulfate Respiratory (Inhalation) Sol: 4mL, 5mL, 300mg
Nebcin/Tobramycin/Tobramycin Sulfate Intramuscular Inj Sol: 1mL, 10mg, 40mg
Nebcin/Tobramycin/Tobramycin Sulfate Intravenous Inj Sol: 1mL, 10mg, 40mg
TOBI Podhaler Respiratory (Inhalation) Pwd: 28mg
Tobramycin/Tobramycin Sulfate Intramuscular Inj Pwd F/Sol: 1.2g
Tobramycin/Tobramycin Sulfate Intravenous Inj Pwd F/Sol: 1.2g
Tobrex Ophthalmic Ointment: 0.3%
Maximum Dosage
Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.
GeriatricInjectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 7.5 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.
AdolescentsInjectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.
Children6 to 12 years: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.
1 to 5 years: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution. Maximum dosage of ophthalmic ointment not established. The safety and efficacy of the nebulized or oral inhalation products have not been established.
2 to 12 months: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution. Maximum dosage of ophthalmic ointment not established. The safety and efficacy of the nebulized or oral inhalation products have not been established.
1 month: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.
8 to 29 days: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 7.5 mg/kg/day IV/IM. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.
0 to 7 days: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 4 mg/kg/day IV/IM. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.
Mechanism Of Action
Tobramycin 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. Tobramycin 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). 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. The uptake of aminoglycosides may be facilitated by the presence of inhibitors of the bacterial cell wall (i.e. beta-lactams, vancomycin).[34041] [34163] [34173] [40042] [41225]
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 PAE can be bacteria specific, as well as drug specific. The PAE of aminoglycosides is short for most gram-positive organisms (less than 2 hours) and longer for gram-negative organisms (2 to 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 to MIC ratio). Both time-kill studies as well as studies in humans have shown that a peak to MIC ratio of more than 8 to 12:1 is associated with successful regimens.[23947] [24566] [34142] [34143] [34144] [34145] [34191] [34192]
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.[34159] [34160] [41226]
The mechanism of ototoxicity relates to the aminoglycoside-induced destruction of sensory hair cells of the inner ear. The cochlear sensory cells that are most vulnerable are in the basal end, thereby leading to high-frequency hearing loss first. As ototoxicity ascends toward the apex of the cochlea, the lower frequencies are affected. Sensory cells that deal with vestibular function may also be affected. Aminoglycosides may cause free-radical damage to sensory cells and neurons. Biochemically, aminoglycosides may bind to polyphosphoinositides, which are part of the transmembrane signaling system mediating physiological effects of hormones, neurotransmitters, and neuromodulators which may interfere with essential mechanisms of cell physiology. Neural destruction without any cochlear hair cell damage has also been described. There may also be a genetic mitochondrial RNA mutation that may predispose some patients to aminoglycoside ototoxicity. Aminoglycosides enter the inner ear rapidly, but it is suggested that aminoglycoside concentrations do not correlate with the development of ototoxicity. Likely, the aminoglycoside concentrations in the inner ear dissipate slowly, which is consistent with the possibility of developing ototoxicity days to weeks after drug discontinuation.[33555] [42984] [42985] [42986]
The susceptibility interpretive criteria for tobramycin are delineated by pathogen. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterobacterales and P. aeruginosa. The MICs are defined for Enterobacterales by FDA as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more; however, the MICs are defined for Enterobacterales by the CLSI as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more (based on a dosage regimen of 7 mg/kg every 24 hours). The MICs are defined for P. aeruginosa by the FDA as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more; however, the MICs are defined for P. aeruginosa by the CLSI as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more (based on a dosage regimen of 7 mg/kg every 24 hours). The MICs are defined for S. aureus, non-Enterobacterales, and Acinetobacter sp. as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more. Interpretive criteria for inhaled tobramycin are not defined. The in vitro susceptibility test methods used for parenteral therapy can be used to monitor the susceptibility of P. aeruginosa isolated from persons with cystic fibrosis; however, breakpoints established for parenteral administration of tobramycin do not apply to aerosolized administration of tobramycin as the relationship between in vitro susceptibility test results and clinical outcome is not clear. A single sputum sample from a person with cystic fibrosis may contain multiple morphotypes of P. aeruginosa which may each have a different level of in vitro susceptibility to tobramycin.
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 P. 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.[34161] [34162] [34163] [41225] Treatment for 6 months with inhaled tobramycin in clinical trials did not affect the susceptibility of the majority of P. aeruginosa isolates tested; however increased MICs were noted in some. The clinical significance of this has not been established in the treatment of P. aeruginosa in persons with cystic fibrosis.
Pharmacokinetics
Tobramycin is administered intravenously, intramuscularly, by oral inhalation, and by ophthalmic administration. Tobramycin is not absorbed orally. It distributes into extracellular fluid; therefore, peak serum concentrations may be lower in patients with a large volume of extracellular fluid. 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 tobramycin is negligible. After administration, tobramycin can be detected in sputum, peritoneal fluid, synovial fluid, and abscess fluid. Tobramycin appears in low concentrations in the CSF, and concentrations are dependent on dose, rate of penetration, and degree of meningeal inflammation.[34037] [34173] [54303]
Tobramycin is not metabolized. Elimination is almost exclusively via glomerular filtration. Thus, elimination half-life varies according to renal function. Reabsorption of a small amount of the drug by the proximal tubule results in accumulation in the renal cortex, which may be responsible for nephrotoxicity. Animal models suggest that tobramycin has a diminished affinity for the proximal tubule. In patients with normal renal function, 93% of the dose is recovered in the urine within 24 hours. The plasma elimination half-life is about 2 to 3 hours in adults with normal renal function. In children with normal renal function, the serum half-life is approximately 1 to 2 hours; however, there is considerable interpatient variation. Biliary excretion is minimal.[34037] [34173] [54381] [54382] Elimination half-lives for the inhaled formulations are approximately 3 hours for TOBI Podhaler and 4.4 hours for Bethkis.[52050] [53821]
Affected cytochrome P450 isoenzymes and drug transporters: none
When tobramycin is administered by intravenous infusion over 1 hour, the serum concentrations are similar to those obtained by intramuscular administration. After an infusion of 1 mg/kg, maximum serum concentrations reach about 4 mcg/mL, and measurable concentrations persist for as long as 8 hours.[49699]
Intramuscular RouteTobramycin is rapidly absorbed after intramuscular administration with peak concentrations occurring between 30 to 90 minutes after administration. After an intramuscular dose of 1 mg/kg, maximum serum concentrations reach about 4 mcg/mL, and measurable concentrations persist for as long as 8 hours.[34037]
Inhalation RouteTobramycin administered via inhalation concentrates primarily in the airways, with bioavailability varying based on airway pathology and nebulizer performance.
Solution for inhalation: The average tobramycin concentration in sputum is 1,237 mcg/g (range: 35 to 7,414 mcg/g) after 10 minutes and 814 mcg/g (range: 23 to 2,843 mcg/g) after 30 minutes. Tobramycin does not accumulate in sputum with repeated dosing. The mean serum tobramycin concentration at 1 hour after inhalation of a single 300 mg dose by cystic fibrosis patients is 0.95 mcg/mL (range: 0.06 to 1.89 mcg/mL); after repeated dosing for 20 weeks, the average serum concentration is 1.05 mcg/mL.
Powder for inhalation: After a single 112 mg dose in cystic fibrosis patients, the mean sputum tobramycin concentration is 1,048 +/- 1,080 mcg/g. A mean peak serum concentration of 1.02 +/- 0.53 mcg/mL is achieved approximately 1 hour post-dose, which is comparable to concentrations observed with a 300 mg dose of TOBI. Systemic exposure is also comparable to the 300 mg TOBI dose (4.6 +/- 2 mcg x hour/mL vs. 4.8 +/- 2.5 mcg x hour/mL). After a 28-day dosing cycle, peak serum concentrations range from 1.48 +/- 0.69 mcg/mL to 1.99 +/- 0.59 mcg/mL.
Pregnancy And Lactation
Systemic exposure to tobramycin may cause fetal harm during pregnancy. Aminoglycosides cross the placenta. There have been reports of total irreversible bilateral congenital deafness in newborns whose mothers received streptomycin, a related aminoglycoside, during pregnancy. Serious side effects to the mother, fetus, or newborn have not been reported with use of other aminoglycosides when used during pregnancy. If tobramycin injection is used during pregnancy or if the patient becomes pregnant during treatment with tobramycin, advise the mother of the potential risk to the fetus.[34037] [54179] Although there are no available data on inhaled tobramycin use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, systemic absorption of tobramycin after inhaled administration is expected to be minimal. There are risks to the mother associated with cystic fibrosis in pregnancy, including preterm delivery.[47300] [53821] [58565] Reproduction studies in animals at doses up to 33 times the normal human systemic dose have revealed no evidence of impaired fertility or harm to the fetus due to ophthalmic tobramycin use. Because animal studies are not always predictive of human response, use ophthalmic tobramycin during pregnancy only if clearly needed.[52361] [52362]
Aminoglycosides are generally excreted into human breast milk in low concentrations. Tobramycin breast milk concentrations after systemic administration are around 0.52 mcg/mL. There are no data on the effects of systemic tobramycin on milk production. Previous American Academy of Pediatrics recommendations considered another aminoglycoside, gentamicin, to be usually compatible with breast-feeding. There are no data on the presence of inhaled tobramycin in either human or animal milk, the effects on the breast-fed infant, or the effects on milk production. Systemic absorption of tobramycin after inhaled administration is expected to be minimal. Serum concentrations after nebulized tobramycin peak at approximately 1 mcg/mL. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tobramycin and any potential adverse effects on the breast-fed infant from tobramycin or the underlying maternal condition. Tobramycin may cause alteration in the intestinal flora of the breast-feeding infant; monitor the breast-fed infant for loose or bloody stools and candidiasis (i.e., thrush, diaper rash). Because of the potential for adverse reactions in nursing infants from ophthalmic tobramycin, discontinue breast-feeding or discontinue ophthalmic tobramycin, taking into account the importance of the drug to the mother.