tobramycin

Inhibits protein synthesis in bacteria at level of 30S ribosome.

Therapeutic effects:

Bactericidal action.

Spectrum:

Most aminoglycosides notable for activity against:
- Pseudomonas aeruginosa,
- Klebsiella pneumoniae,
- Escherichia coli,
- Proteus,
- Serratia,
- Acinetobacter,
- Staphylococcus aureus.
In treatment of enterococcal infections, synergy with a penicillin is required.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after IM administration. IV administration results in complete bioavailability. Low absorption follows administration by inhalation.

Distribution: Widely distributed throughout extracellular fluid; crosses the placenta; small amounts enter breast milk. Poor penetration into CSF.

Metabolism/Excretion: Excretion is >90% renal.

Half-Life: Neonates: 2–11 hr; Infants: 3–5 hr; Children: 1–3 hr; Adolescents: 0.5–2.5 hr; Adults: 2–4 hr (↑ in renal impairment to 5–70 hr).

Time/Action Profile ⬆ ⬇

(plasma concentrations‡)

ROUTE	ONSET	PEAK	DURATION
IM	rapid	30–90 min	6–24 hr
IV	rapid	end of infusion‡	6–24 hr

‡All parenterally administered aminoglycosides.

‡Postdistribution peak occurs 30 min after the end of a 30-min infusion and 15 min after the end of a 1-hr infusion.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Most parenteral products contain bisulfites and should be avoided in patients with known intolerance;
Cross-sensitivity among aminoglycosides may occur;
OB: Pregnancy (may cause congenital deafness with IM/IV administration).

Use Cautiously in:

Renal impairment (dose adjustments necessary);
Hearing impairment;
Mitochondrial DNA variants in the 12S rRNA gene (MTRNR1) or maternal history of ototoxicity (↑ risk of ototoxicity);
Neuromuscular diseases such as myasthenia gravis;
Obese patients (dosage should be based on ideal body weight);
OB: Minimal systemic absorption anticipated with inhalation formulation;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant; minimal systemic absorption with inhalation;
Pedi: Neonates ( risk of neuromuscular blockade; difficulty in assessing auditory and vestibular function; immature renal function);
Geri: Difficulty in assessing auditory and vestibular function in older adults; age-related renal impairment.

Adv. Reactions/Side Effects ⬆ ⬇

EENT: ototoxicity (vestibular and cochlear),

Inhalation only

tinnitus, voice alteration

F and E: hypomagnesemia

GI: CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD)

GU: nephrotoxicity

MS: muscle paralysis (high parenteral doses)

Resp:

Inhalation only

bronchospasm, wheezing

Misc: hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

Inactivated by penicillins and cephalosporins when coadministered to patients with renal insufficiency.
Possible respiratory paralysis after inhalation anesthetics or neuromuscular blockers.
↑risk of ototoxicity with loop diuretics or mannitol (IV).
↑risk of nephrotoxicity with othernephrotoxic drugs.

Route/Dosage ⬆ ⬇

IM IV (Adults ): 3–6 mg/kg/day in 3 divided doses, or 4–6.6 mg/kg once daily.
IM IV (Children >5 yr): 6–7.5 mg/kg/day divided every 8 hr, up to 13 mg/kg/day divided every 6–8 hr in cystic fibrosis patients (dosing interval may vary from every 6 to 24 hr, depending on clinical situation).
IM IV (Children 1 mo–5 yr): 7.5 mg/kg/day divided every 8 hr, up to 13 mg/kg/day divided every 6–8 hr in cystic fibrosis.
IM IV (Neonates ): Preterm <1000 g: 3.5 mg/kg/dose every 24 hr; 0–4 wk, <1200 g: 2.5 mg/kg/dose every 18 hr; Postnatal age <7 days: 2.5 mg/kg/dose every 12 hr; Postnatal age >7 days, 1200–2000 g: 2.5 mg/kg/dose every 8–12 hr; Postnatal age >7 days, >2000 g: 2.5 mg/kg/dose every 8 hr.
Inhaln
(Adults and Children ≥6 yr): Nebulizer solution: 300 mg twice daily for 28 days, then off for 28 days, then repeat cycle; Powder for inhalation: Inhale contents of four 28-mg capsules twice daily for 28 days, then off for 28 days, then repeat cycle.

Renal Impairment

IM IV (Adults ): 1 mg/kg initially; further dosing determined by blood level monitoring and assessment of renal function.

Availability ⬆ ⬇

(Generic available)

Solution for injection: 10 mg/mL; 40 mg/mL
Nebulizer solution (TOBI, Kitabis Pak): 300 mg/5 mL
Nebulizer solution (Bethkis): 300 mg/4 mL
Powder for inhalation (TOBI Podhaler): 28 mg/capsule
Powder for injection: 1200 mg/vial

Assessment ⬆ ⬇

Assess patient for infection (vital signs, wound appearance, sputum, urine, stool, WBC) at beginning of and throughout therapy.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Evaluate eighth cranial nerve function by audiometry before and throughout therapy. Hearing loss is usually in the high-frequency range. Prompt recognition and intervention are essential in preventing permanent damage. Monitor for vestibular dysfunction (vertigo, ataxia, nausea, vomiting). Eighth cranial nerve dysfunction is associated with persistently elevated peak aminoglycoside levels. Aminoglycosides should be discontinued if tinnitus or subjective hearing loss occurs.
Monitor intake and output and daily weight to assess hydration status and renal function.
Assess patient for signs of superinfection (fever, upper respiratory infection, vaginal itching or discharge, increasing malaise, diarrhea).
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.

Lab Test Considerations:

Monitor renal function by urinalysis, specific gravity, BUN, serum creatinine, and CCr before and during therapy.
- May cause ↑ BUN, AST, ALT, serum alkaline phosphatase, bilirubin, creatinine, and LDH concentrations.
- May cause ↓ serum calcium, magnesium, potassium, and sodium concentrations.

Toxicity and Overdose:

Blood levels should be monitored periodically during oral, IM, and IV therapy; not needed for inhalation therapy. Timing of blood levels is important in interpreting results. Draw blood for peak levels 1 hr after IM injection and 30 min after a 30-min IV infusion is completed. Trough levels should be drawn just before next dose. Peak level should not exceed 10 mcg/mL; trough level should not exceed 2 mcg/mL.

Implementation ⬆ ⬇

Keep patient well hydrated (1500–2000 mL/day) during therapy.
IM: Administration should be deep into a well-developed muscle. Alternate injection sites.
Inhaln: Do not mix TOBI or Bethkis with dornase alpha in nebulizer.
- TOBI Podhaler capsules are not for oral use. Store capsules in blister until immediately before use. Use new Podhaler device provided with each weekly packet. Check to see capsule is empty after inhaling. If powder remains in capsule, repeat inhalation until capsule is empty.

IV Administration:

Intermittent Infusion: Diluent: Dilute each dose of tobramycin in 50–100 mL of D5W, D10W, D5/0.9% NaCl, 0.9% NaCl, Ringer’s or lactated Ringer’s solution. Concentration: <10 mg/mL. Pediatric doses may be diluted in proportionately smaller amounts. Stable for 24 hr at room temperature, 96 hr if refrigerated. Also available in commercially mixed piggyback injections.
Rate: Infuse slowly over 30–60 min in both adult and pediatric patients.

Patient/Family Teaching ⬆ ⬇

Instruct patient to report signs of hypersensitivity, tinnitus, vertigo, hearing loss, rash, dizziness, or difficulty urinating.
- Advise patient of the importance of drinking plenty of liquids.
- Instruct patient to notify health care professional immediately if rash, diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care professionals.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Inhaln: Instruct patient to take inhalation twice daily as close to 12 hr apart as possible and not <6 hr apart. Solution is colorless to pale yellow and may darken with age without affecting quality. Administer over 15-min period using a handheld PARI LC PLUS reusable nebulizer with a PARI VIOS (for Bethkis) or DeVibiss Pulmo Aide (for TOBI) compressor. Instruct patient on multiple therapies to take others first and use tobramycin last. Tobramycin-induced bronchospasm may be reduced if tobramycin is administered following bronchodilators. Instruct patient to sit or stand upright during inhalation and breathe normally through mouthpiece of nebulizer. Nose clips may help patient breathe through mouth. Store at room temperature for up to 28 days. Advise patient to disinfect the nebulizer parts (except tubing) by boiling them in water for a full 10 min every other treatment day.
- Instruct patient in correct technique for use of TOBI Podhaler. Wipe mouthpiece with clean, dry cloth after use; do not wash with water.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇