gentamicin

REMS

Serious gram-negative bacterial infections and infections caused by staphylococci when penicillins or other less toxic drugs are contraindicated.
Serious enterococcal infections (in combination with other antibacterial agents).
Prevention of infective endocarditis.
Localized infections due to susceptible organisms.

Action ⬆ ⬇

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

Therapeutic effects:

Bactericidal action.

Spectrum:

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.
Not active against: :
- Streptococci ,
- Anaerobes.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after IM administration. IV administration results in complete bioavailability. Some absorption follows administration by other routes.

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

Metabolism/Excretion: >90% excreted unchanged by kidneys.

Half-Life: Neonates <7 days: 3–11.5 hr; Neonates 7–30 days: 3–6 hr; Infants: 3–5 hr; Children: 1–3 hr; Adolescents: 0.5–2.5 hr; Adults: 2–4 hr (↑ in renal impairment).

Time/Action Profile ⬆ ⬇

(blood levels‡)

ROUTE	ONSET	PEAK	DURATION
IM	rapid	30–90 min	8–24 hr
IV	rapid	15–30 min‡	8–24 hr

‡All parenterally administered aminoglycosides.

‡Post-distribution 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 to gentamicin or other aminoglycosides;
Most parenteral products contain bisulfites and should be avoided in patients with known intolerance;
OB: Pregnancy;
Pedi: Products containing benzyl alcohol should be avoided in neonates.

Use Cautiously in:

Renal impairment (dose adjustments necessary; blood level monitoring useful in preventing ototoxicity and nephrotoxicity);
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;
Pedi: Neonates ( risk of neuromuscular blockade; difficulty in assessing auditory and vestibular function; immature renal function) and neonates on ECMO (require dose adjustments).
Geri: Difficulty in assessing auditory and vestibular function; age-related renal impairment.

Adv. Reactions/Side Effects ⬆ ⬇

EENT: ototoxicity (vestibular and cochlear)

GU: nephrotoxicity

MS: muscle paralysis (high parenteral doses)

Neuro: ataxia, vertigo

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.
↑incidence of ototoxicity with loop diuretics.
↑incidence of nephrotoxicity with other nephrotoxic drugs.

Route/Dosage ⬆ ⬇

Many regimens are used; most involve dosing adjusted on the basis of blood level monitoring and assessment of renal function.
IM IV (Adults ): 1–2 mg/kg every 8 hr (up to 6 mg/kg/day in 3 divided doses); Once-daily dosing (unlabeled): 4–7 mg/kg every 24 hr.
IM IV (Children > 5 yr): 2–2.5 mg/kg/dose every 8 hr. Once daily-5–7.5 mg/kg/dose every 24 hr. Cystic fibrosis-2.5–3.3 mg/kg/dose every 6–8 hr. Hemodialysis-1.25–1.75 mg/kg/dose postdialysis.
IM IV (Children 1 mo-5 yr): 2.5 mg/kg/dose every 8 hr. Once daily-5–7.5 mg/kg/dose every 24 hr. Cystic fibrosis-2.5–3.3 mg/kg/dose every 6–8 hr. Hemodialysis-1.25–1.75 mg/kg/dose postdialysis.
IM IV (Neonates full term and/or > 1 wk): Weight <1200 g-2.5 mg/kg/dose every 18–24 hr. Weight 1200–2000 g-2.5 mg/kg/dose every 8–12 hr. Weight > 2000 g-2.5 mg/kg/dose every 8 hr. ECMO-2.5 mg/kg/dose every 18 hr, subsequent doses based on serum concentrations. Once daily-3.5–5 mg/kg/dose every 24 hr.
IM IV (Neonates premature and/or ≤1 wk): Weight <1000 g-3.5 mg/kg/dose every 24 hr. Weight 1000–1200 g-2.5 mg/kg/dose every 18–24 hr. Weight > 1200 g-2.5 mg/kg/dose every 12 hr. Once daily-3.5–4 mg/kg/dose every 24 hr.
(Adults ): 4–8 mg/day.
(Infants > 3 mo and Children): 1–2 mg/day.
(Neonates ): 1 mg/day.
(Adults and Children > 1 mo): Apply cream or ointment 3–4 times daily.

Renal Impairment

IM IV (Adults ): Initial dose of 2 mg/kg. Subsequent doses/intervals dependent on blood level monitoring and renal function assessment.

Availability ⬆ ⬇

(Generic available)

Premixed infusion: 60 mg/50 mL; 80 mg/50 mL; 80 mg/100 mL; 100 mg/50 mL; 100 mg/100 mL; 120 mg/100 mL
Solution for injection: 10 mg/mL; 40 mg/mL
Topical cream: 0.1%
Topical ointment: 0.1%

Assessment ⬆ ⬇

Assess 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 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 for signs of superinfection (fever, upper respiratory infection, vaginal itching or discharge, increasing malaise, diarrhea).

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, serum creatinine, and LDH concentrations.

Toxicity and Overdose:

Monitor blood levels periodically during 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 levels range 4–6 mcg/mL for adults and 5–12 mcg/mL for children; trough level range not >2 mcg/mL for adults and 0.5–1 mcg/mL for children. Once daily peaks are 2–3 times greater than multiple dosing.

Implementation ⬆ ⬇

Do not confuse gentamicin with gentian violet.
Keep patient well hydrated (1500–2000 mL/day) during therapy.
IM: IM administration should be deep into a well-developed muscle. Alternate injection sites.

IV Administration:

Intermittent Infusion: Diluent: Dilute each dose in 50–200 mL of D5W or 0.9% NaCl.Concentration: Not to exceed 10 mg/mL. Do not use solutions that are discolored or that contain a precipitate.
Rate: Infuse slowly over 30 min–2 hr. For pediatric patients, the volume of diluent may be reduced but should be sufficient to permit infusion over 30 min–1 hr.
Cleanse skin before application. Wear gloves during application.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of gentamicin to patient.
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.
- Teach patients with a history of rheumatic heart disease or valve replacement the importance of using antimicrobial prophylaxis before invasive medical or dental procedures.
Rep: May cause fetal harm. Advise females of reproductive potential use effective contraceptives during therapy and to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor breastfed infants for thrush and diarrhea.
Instruct patient to wash affected skin gently and pat dry. Apply a thin film of ointment. Apply occlusive dressing only if ordered by health care professional. Patient should assess skin and inform health care professional if skin irritation develops or infection worsens.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇