Intramuscular, Intravenous Bacterial septicaemia, Bone infection, Central nervous system infections, Intra-abdominal infections, Respiratory tract infections, Skin and soft tissue infections, Urinary tract infections
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses given 8 hourly. For life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses given 6-8 hourly, then reduce to 3 mg/kg daily as soon as improvement is indicated. Doses are given via IM inj, slow IV inj over 2-3 minutes, or IV infusion over 30-120 minutes. Adjust the dose according to individual response and serum concentration levels of gentamicin. Alternatively, 5-7 mg/kg once daily via IV infusion over 30-120 minutes, then adjusted based on serum gentamicin concentrations. Usual treatment duration: 7-10 days; may be longer for complicated infections. Dosage recommendations may vary among individual products and countries (refer to specific product or local guidelines). Child: Infants and children 6-7.5 mg/kg daily in 3 divided doses given 8 hourly via IM inj or IV infusion over 30-120 minutes. Alternatively, 5-7.5 mg/kg once daily via IV infusion over 30-120 minutes. Adjust the dose according to individual response and serum concentration levels of gentamicin. Usual treatment duration: 7-10 days; may be longer for complicated infections. Dosage recommendations may vary among individual products and countries (refer to specific product or local guidelines).
Adult: As a supplement to systemic treatment: Initially, 1 mg daily via intrathecal or intraventricular inj, may be increased to 5 mg daily if needed. The intrathecal or intraventricular dose is given together with 1 mg/kg 8 hourly IM inj doses. Continue treatment for at least 7 days. Dosage recommendations may vary among individual products and countries (refer to specific product or local guidelines). Child: Same as adult dose.
Ophthalmic Ocular infections
Adult: As 0.3% ophthalmic solution: Instil 1 drop or 2 drops into the affected eye(s) 4 hourly. For severe infections, dose may be increased up to 2 drops hourly. Child: Same as adult dose.
Otic/Aural Otitis externa
Adult: As 0.3% otic solution: Instil 2-3 drops into the affected ear(s) 3-4 times daily and at night, or more frequently if needed. Alternatively, instil 3 drops or 4 drops into the affected ear(s) tid, then reduce gradually as the inflammation subsides. Dosage recommendations may vary among individual products and countries (refer to specific product or local guidelines). Child: As 0.3% otic solution: Instil 2-3 drops into the affected ear(s) 3-4 times daily and at night, or more frequently if needed.
Topical/Cutaneous Skin infections
Adult: As 0.1% ointment/cream or 0.3% cream: Apply a small amount 3-4 times daily to the affected area. Treated areas may be covered with gauze dressing if necessary. Child: ≥1 year As 0.1% ointment or cream: Same as adult dose.
Special Patient Group
Pharmacogenomics:
Gentamicin is an aminoglycoside antibiotic that inhibits bacterial protein synthesis by binding to the 16S ribosomal RNA (rRNA) subunit of the bacterial 30S ribosome, which is responsible for messenger RNA (mRNA) translation within the prokaryotic cell.
The MT-RNR1 gene encodes the human 12S rRNA subunit, the mitochondrial homologue of the prokaryotic 16S rRNA subunit. Certain MT-RNR1 gene variants may cause the human 12S rRNA subunit to resemble the bacterial 16S rRNA subunit more closely, thereby allowing the aminoglycosides to bind more readily. The presence of MT-RNR1 gene variants may increase the risk of aminoglycoside-induced ototoxicity (including potentially significant hearing loss) even when serum levels are within the normal range.
Although MT-RNR1 gene variants are rare and penetrance is uncertain, genetic testing may be considered but the testing should not delay urgently needed aminoglycoside treatment.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of May 2021:
Phenotype and Genotype
Implications
Recommendations
MT-RNR1 increased risk of aminoglycoside-induced hearing loss
Patients with MT-RNR1 variant associated with increased risk of aminoglycoside-induced hearing loss e.g. m.1095T>C, m.1494C>T, m.1555A>G
Very high risk of developing hearing loss if gentamicin is administered.
Avoid the use of gentamicin unless the increased risk of permanent hearing loss is outweighed by the severity of the infection and the lack of alternative therapies. If no effective alternative is available, frequently evaluate patients for hearing loss during treatment and ensure all appropriate precautions are utilised (e.g. lowest possible dose, shortest possible duration, renal function and therapeutic drug monitoring, hydration).
MT-RNR1 normal risk of aminoglycoside-induced hearing loss
Patients with no detectable MT-RNR1 increased risk variant or MT-RNR1 variant associated with normal risk of aminoglycoside-induced hearing loss e.g. m.827A>G
Normal risk of developing hearing loss if gentamicin is administered.
Use gentamicin at standard doses for the shortest possible course with therapeutic drug monitoring. Regularly evaluate for hearing loss in accordance with the local guidelines.
MT-RNR1 uncertain risk of aminoglycoside-induced hearing loss
Patients with MT-RNR1 variant associated with uncertain risk of aminoglycoside-induced hearing loss e.g. m.663A>G, m.669T>C, m.747A>G, m.786G>A, m.807A>G, m.807A>C, m.839A>G, m.896A>G, m.930A>G, m.951G>A, m.960C>del, m.961T>G, m.961T>del, m.961T>del+Cn, m.988G>A, m.1189T>C, m.1243T<62>C, m.1520T>C, m.1537C<62>T, m.1556C>T
Weak or no evidence of increased risk of MT-RNR1-associated hearing loss if gentamicin is administered.
Use gentamicin at standard doses for the shortest possible course with therapeutic drug monitoring. Regularly evaluate for hearing loss in accordance with the local guidelines.
Renal Impairment
Bacterial septicaemia; Bone infection; Central nervous system infections; Intra-abdominal infections; Respiratory tract infections; Skin and soft tissue infections; Urinary tract infections:
Dose and/or dosing interval adjustment may be required based on clinical response and degree of renal impairment (refer to specific product or local guidelines).
Reconstitution
IV infusion: Adults: Dilute the required dose in 50-200 mL NaCl 0.9% solution or dextrose 5% in water. Children: Dilute using a smaller volume of NaCl 0.9% solution or dextrose 5% in water depending on the patient's needs to prepare a concentration of 1-10 mg/mL. Intrathecal/intraventricular inj: Adults: Use a preservative-free preparation only. Children: Use a preservative-free gentamicin preparation; before administration, dilute in preservative-free NaCl 0.9% solution to a final concentration of 1-5 mg/mL. Recommendations for dilution and concentration may vary among individual products and countries (refer to specific product or local guidelines).
Incompatibility
IM/IV/Intrathecal/Intraventricular: Incompatible with penicillins, cephalosporins, erythromycin, heparin, furosemide, Na bicarbonate, and preparations with alkaline pH (e.g. aciclovir, sulfadiazine Na).
Contraindications
Hypersensitivity to gentamicin or other aminoglycosides. Myasthenia gravis. Known or suspected perforated tympanic membrane (otic).
Special Precautions
Patient with family history of ototoxicity, pre-existing vertigo, tinnitus, or hearing loss; neuromuscular disorders (e.g. parkinsonism); hypocalcaemia, hypokalaemia, hypomagnesaemia; significant obesity. Dehydrated patients. Patients with certain MT-RNR1 gene variants. Not intended for long-term treatment (otic/ophthalmic/topical). Avoid concomitant or sequential use of other neurotoxic and/or nephrotoxic drugs, and concomitant use with potent diuretics. Renal impairment. Neonates, children, and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Nephrotoxicity (reversible), neurotoxicity manifested by ototoxicity (both vestibular and auditory effects); neuromuscular blockade, respiratory paralysis; bacterial or fungal superinfection (prolonged use), including Clostridioides difficile-associated diarrhoea and pseudomembranous colitis; severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis), hypersensitivity reactions; delayed corneal healing (ophthalmic); local sensitisation, including burning or stinging sensation and irritation (otic/ophthalmic/topical). Blood and lymphatic system disorders: Anaemia, agranulocytosis, granulocytopenia, leucopenia, thrombocytopenia, eosinophilia. Eye disorders: Blurred vision, eye pruritus, bacterial and fungal corneal ulcers, non-specific conjunctivitis, conjunctival epithelial defects, conjunctival hyperaemia. General disorders and administration site conditions: Inj site pain, fever. Gastrointestinal disorders: Vomiting, nausea, stomatitis, increased salivation. Investigations: Increased serum transaminases, weight loss. Metabolism and nutrition disorders: Hypomagnesaemia (prolonged use); decreased appetite. Musculoskeletal and connective tissue disorders: Arthralgia, muscle weakness. Nervous system disorders: Headache, myasthenia gravis-like syndrome, convulsions, lethargy, peripheral neuropathy or encephalopathy. Psychiatric disorders: Depression, confusion, hallucinations. Renal and urinary disorders: Oliguria, Fanconi-like syndrome, acute renal failure. Skin and subcutaneous tissue disorders: Rash, pruritus, purpura, urticaria, alopecia; dermatitis (otic/ophthalmic); erythema (topical).
Ophthalmic: This drug may cause transient blurring of vision, if affected, do not drive or operate machinery. Remove contact lenses prior to instillation of eye drops and wait for at least 15 minutes before reinserting the lenses.
Monitoring Parameters
Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Obtain urine output, urinalysis, BUN, serum creatinine, or CrCl periodically. Closely monitor peak and trough serum gentamicin concentrations periodically (especially for systemic treatment); eighth cranial nerve function (particularly in patients with known or suspected renal impairment); hearing function prior to initiation, during and after treatment. Assess for signs and symptoms of serious skin reactions, ototoxicity, neurotoxicity and nephrotoxicity.
Overdosage
Symptoms: Nephrotoxicity (e.g. oliguria, increased serum creatinine) and neurotoxicity (e.g. dizziness, vertigo, tinnitus, ataxia). Management: Consider haemodialysis or peritoneal dialysis to help remove gentamicin in the blood.
Drug Interactions
Increased risk of ototoxicity with potent diuretics (e.g. etacrynic acid, furosemide). Enhanced neurotoxic and/or nephrotoxic effects with other aminoglycosides (e.g. amikacin, neomycin), vancomycin, viomycin, colistin, amphotericin B, polymyxin B, cisplatin, ciclosporin, and cephalosporins (particularly cefaloridine). May increase the risk of neuromuscular blockade and respiratory paralysis with neuromuscular blocking agents (e.g. suxamethonium, decamethonium, tubocurarine). Increased risk of hypocalcaemia with bisphosphonates. May decrease thrombin levels and increase the risk of bleeding with oral anticoagulants. May antagonise the effects of neostigmine or pyridostigmine. Concomitant use with indometacin may increase the plasma gentamicin concentrations in neonates.
Action
Description: Mechanism of Action: Gentamicin is an aminoglycoside antibiotic with broad-spectrum bactericidal action. It inhibits bacterial protein synthesis by binding to 30S ribosomal subunit, resulting in a defective bacterial cell membrane. Pharmacokinetics: Absorption: Rapidly and completely absorbed following IM administration. Systemic absorption may occur after ophthalmic, otic and topical (particularly on denuded skin and burns) application. Time to peak plasma concentration: 30-90 minutes (IM); 30-60 minutes (IV infusion over 2 hours). Distribution: Diffuses mainly into extracellular fluids and readily into the perilymph of the inner ear; high concentration in the renal cortex; minimal penetration into CSF and ocular tissues. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.2-0.3 L/kg. Plasma protein binding: <30%. Excretion: Via urine (≥70% as unchanged drug). Elimination half-life: Approx 2-3 hours.
Chemical Structure
Gentamicin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3467, Gentamicin. https://pubchem.ncbi.nlm.nih.gov/compound/Gentamicin. Accessed Aug. 18, 2023.
Storage
IM/IV inj: Store intact vials between 20-25°C. Do not freeze. Diluted IV infusions: May be stored at room temperature or under refrigeration for 48 hours. Intrathecal/intraventricular inj: Store in a cold place. Ophthalmic/otic solution: Store below 25°C. Protect from excessive heat. Topical cream/ointment: Store between 15-30°C. Storage recommendations may vary between individual products or countries (refer to detailed product guidelines).
J01GB03 - gentamicin ; Belongs to the class of other aminoglycosides. Used in the systemic treatment of infections. D06AX07 - gentamicin ; Belongs to the class of other topical antibiotics used in the treatment of dermatological diseases. S03AA06 - gentamicin ; Belongs to the class of antiinfectives used in ophthalmologic and otologic preparations. S02AA14 - gentamicin ; Belongs to the class of antiinfectives used in the treatment of ear infections. S01AA11 - gentamicin ; Belongs to the class of antibiotics. Used in the treatment of eye infections.
References
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