Pseudomonal and other gram negative infections, inhaled form used in cystic fibrosis
Monitor creatinine at kest weekly and more often if levels are elevated or other signs of renal dysfunction arise. Discontinue if any signs of ototoxicity (tinnitus, fullness in ears, dizziness).
Serum Level Monitoring for EXTENDED Interval Dosing, pediatrics: For most patients and indications, no levels are necessary, unless: Patients suspected at high risk for development of nephrotoxicity or renal dysfunction, or duration of treatment more than 5 days. In these cases check trough level prior to any dose to ensure that it is less than 1 mg/L. In cases where there is concern regarding treatment efficacy due to lack of response or severe infection treated with monotherapy, for cystic fibrosis (CF) or febrile neutropenia: Draw TWO levels, one 2 to 3 hours and one 6 to 8 hours after first dose. Refer to Calgary Zone Once Daily Aminoglycoside Calculator (in monograph) to calculate target parameters
Serum Level Monitoring for EXTENDED Interval Dosing, neonates: If plan is to discontinue tobramycin pending 48-hour culture results, no levels are required unless indicated for renal dysfunction. If plan is to continue antibiotics beyond 48 h culture resutls, draw a 22 hour level on all neonates regardless of ordered dosing interval.
If 22 h level is: 1.2 mcg/mL or less- give every 24h.
1.3 to 2.6 mcg/mL- give every 36h
2.7 to 3.5 mcg/mL- give every 48h
3.6 mcg/mL or more- Hold next dose, repeat level in 24 hours. Base interval on time to reach trough level less than 2 mcg/mL. Repeat 22h level if therapy continues beyond 7 days.
Serum Level Monitoring for CONVENTIONAL Dosing: Obtain drug levels with the third or fourth dose. Peak serum levels are drawn 30 minutes after the end of an IV infusion or one hour post-IM injection. Peak levels are: 5 to 10 mcg/mL and 12 to 15 mcg/mL in cystic fibrosis. Trough levels are drawn just prior to the next dose and should be less than 2 mcg/mL.
Serum Level Monitoring for Synergistic Dosing: Levels are typically not required. If done, targets are: Peak 3 to 5 mg/L and trough less than 2 mg/L.
Nephrotoxicity (non-oliguric) - less common with once daily dosing; greater toxicity with longer duration and supratherapeutic trough levels; avoid concomitant nephrotoxins
Vestibulocochlear toxicity (irreversible)- suggest audiology testing if prolonged use
Can exacerbate neuromuscular blockade- e.g. contraindicated in patients with myasthenia gravis.
Enhanced nephrotoxic effect with concomitant use of other nephrotoxins
Enhanced ototoxicity with loop diuretics (e.g. furosemide).
Non-depolarizing muscle relaxants may be potentiated.
Antimicrobial class: Aminoglycoside
Average serum half life: Neonates: ≤1200 g: 11 hours, >1,200 g: 2 to 9 hours.
Infants: 4 ± 1 hour.
Children: 2 ± 1 hour.
Adolescents: 1.5 ± 1 hour
Adults: IV: 1-2 hours; directly dependent upon glomerular filtration rate
Adults with impaired renal function: 5- 70 hours
Route of Elimination: With normal renal function, 93% of dose excreted in urine within 24 hours