Amikacin


Generic Medicine Info
Indications and Dosage
Inhalation/Respiratory
Mycobacterium avium complex infections
Adult: As part of an antibacterial regimen in patients with refractory Mycobacterium avium complex (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).

Intramuscular, Intravenous
Uncomplicated urinary tract infections
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.

Intramuscular, Intravenous
Severe Gram-negative infections, Susceptible Gram-negative infections, Susceptible staphylococcal infections
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.
Elderly: Dose reduction may be required.
Child: 4 weeks to 12 years 15-20 mg/kg daily as a single dose, or 7.5 mg/kg 12 hourly; 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.

Special Patient Group
Pharmacogenomics:

Amikacin 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, which is the mitochondrial homologue of the prokaryotic 16S rRNA subunit. Some variants in the MT-RNR1 gene appear to cause the human 12S rRNA subunit to resemble the bacterial 16S rRNA subunit more closely, therefore allowing the aminoglycosides to bind more readily. The presence of these gene variants may increase the risk of aminoglycoside-induced ototoxicity, including 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 amikacin is administered. Avoid the use of amikacin 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 employed (e.g. shortest possible duration, lowest possible dose, renal function monitoring, therapeutic drug monitoring, hydration).
MT-RNR1 normal risk of aminoglycoside-induced hearing loss

Patients with no detectable MT-RNR1 increased risk variant or variant associated with normal risk of aminoglycoside-induced hearing loss e.g. m.827A>G
Normal risk of developing hearing loss if amikacin is administered. Use amikacin at standard doses for the shortest possible time 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>C, m.1520T>C, m.1537C>T, m.1556C>T
Weak or no evidence of increased risk of MT-RNR1-associated hearing loss if amikacin is administered. Use amikacin at standard doses for the shortest possible time course with therapeutic drug monitoring. Regularly evaluate for hearing loss in accordance with the local guidelines.
Renal Impairment
Intravenous/Intramuscular:
Dosage adjustment may be needed.
Reconstitution
IV infusion: Dilute with an appropriate volume of compatible IV infusion fluid (e.g. NaCl 0.9%, dextrose 5%). Refer to specific product or local guidelines for further instructions on reconstitution. 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 B, 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, hearing loss, vestibular damage; family history of aminoglycoside-induced deafness; neuromuscular disorders (e.g. Parkinson's disease), hypocalcaemia. Dehydrated patients. Used as a 2nd-line treatment for staphylococcal infections. Patients with certain MT-RNR1 gene variants (e.g. m.1555A>G). Renal impairment. 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.
IM/IV/Parenteral: D
Monitoring Parameters
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 trough 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 signs, temperature, weight, 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, cefaloridine, paromomycin, polymyxin B, colistin, tacrolimus, vancomycin, viomycin, IV mannitol, or other aminoglycosides. Increased risk of ototoxicity with potent diuretics (e.g. etacrynic 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 indometacin in neonates.
Action
Description:
Mechanism of Action: 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: 0-11% (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

Chemical Structure Image
Amikacin

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 37768, Amikacin. https://pubchem.ncbi.nlm.nih.gov/compound/Amikacin. Accessed Aug. 15, 2023.

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.
MIMS Class
Aminoglycosides
ATC Classification
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
Hughes KM, Johnson PN, Anderson MP et al. Comparison of Amikacin Pharmacokinetics in Neonates Following Implementation of a New Dosage Protocol. J Pediatr Pharmacol Ther. 2017;22(1):33-40. doi: 10.5863/1551-6776-22.1.33. Accessed 15/05/2023. PMID: 28337079

McDermott JH, Wolf J, Hoshitsuki K et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical Pharmacology & Therapeutics. 2022 Feb;111(2):366-372. doi: 10.1002/cpt.2309. Accessed 19/04/2023

Committee on Infectious Diseases, American Academy of Pediatrics, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH. "Tables of Antibacterial Drug Dosages", Red Book: 2021-2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics [online]. Accessed 24/03/2023.

Amikacin 250 mg/2 mL Injection (Pharmaniaga Lifescience Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 19/04/2023.

Amikacin 250 mg/mL Injection (Hospira UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 19/04/2023.

Amikacin Sulfate Injection (Hikma Pharmaceuticals USA Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/04/2023.

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.

Amikacin. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 19/04/2023.

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.

Annotation of CPIC Guideline for Amikacin, Gentamicin, Kanamycin, Paromomycin, Plazomicin, Streptomycin, Tobramycin and MT-RNR1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 19/04/2023.

Anon. Amikacin (Oral Inhalation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/04/2021.

Anon. Amikacin (Systemic) (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/04/2023.

Anon. Amikacin (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/04/2023.

Anon. Amikacin Sulfate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 19/04/2023.

Anon. MT-RNR1 - Amikacin (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/04/2023.

Arikayce (Insmed 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 19/04/2023.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Aminoglycosides Based on MT-RNR1 Genotype. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org. Accessed 19/04/2023.

Joint Formulary Committee. Amikacin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/04/2023.

Paediatric Formulary Committee. Amikacin. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 19/04/2023.

Pfizer New Zealand Limited. DBL Amikacin 500 mg/2 mL Solution for Injection data sheet 18 May 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 19/04/2023.

Disclaimer: This information is independently developed by MIMS based on Amikacin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com
  • Apalin
  • DBL Amikacin
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Already a member? Sign in
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Already a member? Sign in