Optimizing Amikacin Therapy: A Comprehensive Guide to Therapeutic Drug Monitoring for Enhanced Efficacy and Safety

This presentation provides an in-depth exploration of Therapeutic Drug Monitoring (TDM) for amikacin, focusing on optimizing its efficacy and safety. It covers the principles of pharmacokinetics and dosing strategies, and clinical guidelines to minimize toxicity and maximize therapeutic outcomes. Ideal for healthcare professionals, pharmacists, and medical students, this guide aims to give a brief headsup on application of TDM in clinical practice.

1. TDM OF AMIKACIN Prepared By Dr Aman Suresh T Assistant Professor Department of Pharmacy Practice Sandip Institute of Pharmaceutical Sciences, Nashik

2. CONTENTS: Introduction Clinical applications Mechanism of action Immunoassay of Amikacin Pharmacokinetics parameters Toxicity Monitoring of Amikacin therapy Drug interactions Contraindications Adverse drug reaction.

3. Introduction: Amikacin is a potent aminoglycoside antibiotic renowned for its effectiveness against multidrug-resistant Gram-negative pathogens.

4. Clinical applications: Amikacin finds several clinical applications due to its broad-spectrum activity against Gram-negative bacteria and some Gram-positive bacteria. The Clinical Applications are Serious and Hospital Acquired Infections Neonatal Infections Combination Therapy Tuberculosis Cystic Fibrosis Various Bacterial and Multi-resistant cases For Sepsis or endocarditis For MDR-TB Respiratory issues with Cystic Fibrosis

5. Mechanism of action: Mechanism of Resistance Resistance is due to mutation in codons-1400,1401 and 1483 of rrs gene of 16S rRNA of 30S Small ribosomal Subunit

6. Immunoassay of Amikacin Enzyme Linked Immunosorbent Assay Radioimmunoassay Fluorescent Immunoassay Chemiluminescent Immunoassay

7. Pharmacokinetic parameters: Absorption Administration: Given intravenously (IV) or intramuscularly (IM). Bioavailability: 100% with IV administration, rapid and complete absorption with IM . Distribution: Volume of Distribution ( Vd ): 0.2-0.3 L/kg, indicating moderate distribution mainly in extracellular fluids. Protein Binding: Low (<10%), meaning most of the drug remains free and active. Tissue Penetration: Effective penetration in extracellular fluids, urine, and peritoneal fluid; poor penetration into cerebrospinal fluid (CSF ).

8. Metabolism: Metabolic Pathway: Not significantly metabolized by the liver. Metabolites : None; excreted largely unchanged . Elimination: Half-life: 2-3 hours in individuals with normal renal function, prolonged in renal impairment. Excretion: Primarily through the kidneys by glomerular filtration. Clearance: 80-100 mL/min in individuals with normal renal function .

9. Toxicity parameters of Amikacin Nephrotoxicity: Incidence: Occurs in 5-25% of patients, dependent on dosage and duration. Mechanism: Accumulation in renal proximal tubule cells leading to cell damage. Monitoring: Regular serum creatinine and BUN (blood urea nitrogen) levels. Risk Factors: Pre-existing renal impairment, concurrent nephrotoxic drugs, prolonged therapy

10. Ototoxicity: Incidence: Occurs in 1-10% of patients, can be irreversible. Mechanism: Accumulation in the inner ear, damaging hair cells of the cochlea and vestibular apparatus. Symptoms: Hearing loss, tinnitus, balance disturbances. Monitoring: Audiometric tests before and during therapy, especially in high-risk patients. Risk Factors: Prolonged therapy, high peak plasma levels, genetic predisposition (e.g., mitochondrial mutations).

11. Neuromuscular Blockade: Incidence: Rare but can occur with high doses or rapid administration. Mechanism: Interference with neurotransmitter release at the neuromuscular junction. Symptoms: Respiratory depression, muscle weakness. Monitoring: Clinical observation, especially in patients with myasthenia gravis or other neuromuscular disorders. Risk Factors: Concurrent use of neuromuscular blocking agents, general anaesthesia.

12. Monitoring Of Amikacin Therapy: Peak Levels : 20-30 µg/mL (measured 30-60 minutes after administration ). Trough Levels : <5 µg/mL (measured just before the next dose ). Adjustments : Dosage adjustments based on TDM to avoid toxicity.

13. Interaction: Amikacin shows interaction with the following drugs Vancomycin Amphotericin B Cisplatin Cyclosporine NSAIDs (ibuprofen , naproxen ) Loop Diuretics (furosemide , bumetanide ) Atracurium Cephalosporins (ceftriaxone , cefuroxime, cefotaxime ) Acyclovir Ethacrynic acid Tacrolimus Aminoglycosides (gentamicin, tobramycin, neomycin) Succinylcholine

14. Adverse Drug Reactions: Elevated serum creatinine Proteinuria Hearing loss Tinnitus Dizziness Vertigo Fever Pain Redness Muscle weakness Respiratory depression (rare, but possible in high doses or with rapid administration) Rash

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