Adult: As part of an antibacterial regimen in patients with refractory MAC lung disease who have limited treatment options: 1 vial (590 mg) once daily, using the inhalation delivery system provided (refer to specific product guideline).
Adult: In cases not caused by Pseudomonas infections: 7.5 mg/kg daily in 2 equally divided doses (or 250 mg bid) via IM inj, slow IV inj over 2-3 minutes or IV infusion over 30-60 minutes. Max: 1.5 g daily; 15 g (total dose). Usual treatment duration: 7-10 days. Elderly: Dose reduction may be required.
Adult: 15 mg/kg daily as a single or in 2-3 equally divided doses; in patients with endocarditis or febrile neutropenia, doses should be given bid. In life-threatening cases and/or those caused by Pseudomonas infections: 500 mg 8 hourly. Max: 1.5 g daily; 15 g (total dose). Usual treatment duration: 7-10 days. Doses may be given via IM inj, slow IV inj over 2-3 minutes or IV infusion over 30-60 minutes. Dose is adjusted based on the patient's body weight and serum amikacin concentration. Child: Premature infants 7.5 mg/kg 12 hourly; Neonates Initially, 10 mg/kg followed by 7.5 mg/kg 12 hourly; 4 weeks to 12 years 15-20 mg/kg daily as single or in 2 equally divided doses; in patients with endocarditis or febrile neutropenia, doses should be given bid. Usual treatment duration: 7-10 days. Doses may be given via IM inj or IV infusion over 30-60 minutes or 1-2 hours (in infants). Dose is adjusted based on the patient's body weight and serum amikacin concentration. Elderly: Dose reduction may be required.
Special Patient Group
Current studies suggest an increased risk of aminoglycoside ototoxicity in patients with mitochondrial mutations, particularly the homoplasmic m.1555A>G mutation in the highly conserved decoding site of the 12s rRNA, including patients with serum aminoglycoside levels within the recommended range. Additionally, some cases have occurred in families with maternally transmitted deafness. Genetic testing may be considered before starting recurrent or long-term treatment but should not delay urgently needed aminoglycoside therapy.
These mitochondrial mutations are rare, and the penetrance is uncertain. Furthermore, patients with the 1555G allele who are taking an aminoglycoside antibiotic, may have an increased risk of experiencing drug-induced hearing loss than in patients with the 1555A allele. The mechanism of how the heteroplasmy affects the severity of occurrence of aminoglycoside-induced hearing loss remains unclear, although other genetic or clinical factors may contribute to the risk of aminoglycoside-induced hearing loss.
Renal Impairment
IV/IM:
Dosage adjustment may be needed.
Reconstitution
IV infusion: Dilute with 0.9% NaCl or 5% dextrose in water. Inhalation: Shake the vial well for at least 10-15 seconds until a uniform mixture is achieved, then pour directly into the medication reservoir of the nebuliser handset.
Incompatibility
Incompatible with amphotericin chlorothiazide Na, erythromycin gluceptate, heparin, nitrofurantoin Na, phenytoin Na, thiopentone Na, warfarin Na, some penicillins and cephalosporins.
Contraindications
Hypersensitivity to amikacin and other aminoglycoside antibiotics. Myasthenia gravis. Concomitant or sequential administration of oral or topical drugs that are neurotoxic, ototoxic or nephrotoxic; concomitant use with potent diuretics.
Special Precautions
Patient with pre-existing vertigo, tinnitus, or hearing loss, vestibular damage; neuromuscular disorders (e.g. Parkinson's disease), hypocalcaemia. Dehydrated patients. Used as a 2nd-line treatment for staphylococcus infections. Patients with m.1555A>G mutation. Renal impairment. Premature infants, neonates, children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Hypersensitivity, neurotoxicity, ototoxicity, nephrotoxicity, neuromuscular blockade, respiratory paralysis, fungal or bacterial superinfection, Clostridium difficile associated diarrhoea (CDAD), pseudomembranous colitis (prolonged use). Inhalation: Bronchospasm, haemoptysis, hypersensitivity pneumonitis and alveolitis; COPD, infective exacerbation of COPD or bronchiectasis. Blood and lymphatic system disorders: Anaemia, eosinophilia. Ear and labyrinth disorders: Tinnitus, hypoacusis, vertigo. Gastrointestinal disorders: Nausea, vomiting; diarrhoea, dry mouth, laryngitis, oral candidiasis, dysgeusia (inhalation). General disorders and administration site conditions: Pyrexia, injection site pain (IM); fatigue (inhalation). Investigations: Decreased weight (inhalation). Metabolism and nutrition disorders: Hypomagnesaemia. Musculoskeletal and connective tissue disorders: Arthralgia, muscle twitching; musculoskeletal pain (inhalation). Nervous system disorders: Balance disorder, headache, paraesthesia, tremor. Renal and urinary disorders: Oliguria, albuminuria, azotaemia, RBC urine, WBC urine. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, dysphonia, wheezing, increased sputum, vocal cord inflammation, throat irritation, oropharyngeal pain (inhalation). Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria. Vascular disorders: Hypotension.
Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor renal function, urine (e.g. specific gravity, excretion of proteins, presence of cells or casts), BUN, creatinine, appropriately timed peak and through concentrations, eighth cranial nerve function (especially in patients with known or suspected renal impairment). Perform hearing tests (audiograms) at baseline and periodically. Assess for signs and symptoms of ototoxicity, neurotoxicity and nephrotoxicity; vital sigs, temperature, weigh, input and output.
Overdosage
Symptoms: Nephrotoxicity, ototoxicity and neuromuscular blockade with respiratory arrest. Management: Administer ionic Ca (e.g. as gluconate or lactobionate in 10-20% solution) to treat neuromuscular blockade with respiratory arrest. Perform either peritoneal dialysis, haemodialysis, or continuous arteriovenous haemofiltration to reduce serum amikacin levels.
Drug Interactions
Additive neurotoxic, ototoxic or nephrotoxic effects with amphotericin B, bacitracin, cisplatin, ciclosporin, cephaloridine, paromomycin, polymyxin B, colistin, tacrolimus, vancomycin, viomycin, IV mannitol, or other aminoglycosides. Increased risk of ototoxicity with potent diuretics (e.g. ethacrynic acid or furosemide); may increase risk of toxicity with IV diuretics. May increase risk of respiratory paralysis with anaesthetics or neuromuscular blocking agents (e.g. tubocurarine, succinylcholine, decamethonium, atracurium, rocuronium, vecuronium, opioid analgesic, massive transfusions with citrated anticoagulated blood). Increased risk of nephrotoxicity and may increase serum creatinine levels with cephalosporins. May reduce antibacterial activity with penicillins. Increased risk of hypocalcaemia with bisphosphonates. Increased risk of nephrotoxicity and ototoxicity with platinum drugs. May increase serum concentration with indomethacin in neonates.
Action
Description: Amikacin, an antibiotic with bactericidal activity, inhibits bacterial protein synthesis by irreversibly binding to 30S ribosomal subunits. Pharmacokinetics: Absorption: Rapidly absorbed (IM); variable (inhalation). Time to peak plasma concentration: 1 hour (IM); within 30 minutes (IV). Distribution: Readily diffuses into extracellular fluids (highly hydrophilic) but poorly penetrates the blood-brain barrier (even with inflamed meninges). Crosses the placenta and enters breast milk. Volume of distribution: 0.25 L/kg (systemic); 5.0 L/kg (inhalation). Plasma protein binding: ≤20% (systemic); ≤10% (inhalation). Excretion: Via urine (94-98%, as unchanged drug [systemic]; 7.42% as unchanged drug [inhalation]). Elimination half-life: 2-3 hours (systemic); approx 5.9-19.5% (inhalation).
Chemical Structure
Amikacin Source: National Center for Biotechnology Information. PubChem Database. Amikacin, CID=37768, https://pubchem.ncbi.nlm.nih.gov/compound/Amikacin (accessed on Jan. 20, 2020)
Storage
Parenteral: Store below 25°C. Diluted solution may be stored below 25°C for up to 24 hours. Inhalation: Store between 2-8°C. Do not freeze. Can be stored below 25°C for up to 4 weeks.
D06AX12 - amikacin ; Belongs to the class of other topical antibiotics used in the treatment of dermatological diseases. S01AA21 - amikacin ; Belongs to the class of antibiotics. Used in the treatment of eye infections. J01GB06 - amikacin ; Belongs to the class of other aminoglycosides. Used in the systemic treatment of infections.
References
Gao Z, Chen Y, Guan MX. Mitochondrial DNA Mutations Associated with Aminoglycoside-Induced Ototoxicity. Journal of Otology. 2017;12(1):1-8. doi: 10.1016/j.joto.2017.02.001. Accessed 29/01/2021Li Z, Li R, Chen J, et al. Mutational Analysis of the Mitochondrial 12S rRNA Gene in Chinese Pediatric Subjects with Aminoglycoside-Induced and Non-Syndromic Hearing Loss. Hum Genet. 2005;117(1):9-15. doi: 10.1007/s00439-005-1276-1. Accessed 29/01/2021. PMID: 15841390Amikacin 250 mg/mL Injection (Hospira UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 20/01/2021.Amikacin Sulfate Injection, Solution (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 20/01/2021.Aminoglycosides (Gentamicin, Amikacin, Tobramycin, and Neomycin): Increased Risk of Deafness in Patients with Mitochondrial Mutations. Medicines & Healthcare products Regulatory Agency. https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency. Accessed 29/01/2021.Anon. Amikacin (Inhalation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/04/2021.Anon. Amikacin (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/01/2021.Arikayce (Insumed Incorporated). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/04/2021.Arikayce Liposomal 590 mg Nebuliser Dispersion (Almac Pharma Services [Ireland] Ltd.). European Medicines Agency [online]. Accessed 19/04/2021.Buckingham R (ed). Amikacin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/01/2021.Clinical Annotation for rs267606617(MT-RNR1); Amikacin, Aminoglycoside Antibacterials, Gentamycin, Kanamycin, Neomycin, Streptomycin or Tobramycin; Ototoxicity (Level 1B Toxicity/ADR). Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 29/01/2021.Joint Formulary Committee. Amikacin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/01/2021.Pfizer New Zealand Limited. DBL Amikacin 500 mg/2 mL Solution for Injection data sheet 1 February 2019. Medsafe. http://www.medsafe.govt.nz. Accessed 20/01/2021.
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