Amikacin

Usage

Amikacin is prescribed for serious infections caused by susceptible strains of Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, Proteus species, Klebsiella species, Enterobacter species, Serratia species, and Acinetobacter species. It is also effective against some Gram-positive bacteria, such as Staphylococcus species, and is occasionally used to treat multi-drug resistant tuberculosis when other treatments have failed.

It is classified as an aminoglycoside antibiotic.

Amikacin’s mechanism of action involves irreversible binding to the bacterial 30S ribosomal subunit, inhibiting protein synthesis and leading to bacterial cell death.

Alternate Names

Amikacin Sulfate is the official chemical name. There are numerous brand names worldwide, with Amikin being a previously popular brand name (now discontinued in some countries). Other brand names may be available regionally.

How It Works

Pharmacodynamics: Amikacin exerts its bactericidal effect by irreversibly binding to the 30S ribosomal subunit of susceptible bacteria. This binding interferes with protein synthesis by causing misreading of mRNA and ultimately leading to cell death.

Pharmacokinetics:

• Absorption: Administered intravenously (IV) or intramuscularly (IM). Not absorbed orally. IM absorption is rapid.
• Distribution: Distributes widely into most body fluids and tissues, including pleural, peritoneal, and synovial fluids. Limited penetration into cerebrospinal fluid (CSF), but penetration increases with meningeal inflammation.
• Metabolism: Minimal metabolism.
• Elimination: Primarily excreted unchanged in the urine by glomerular filtration. Elimination half-life is prolonged in patients with renal impairment.

Mode of Action: Amikacin targets the bacterial 30S ribosomal subunit, specifically the decoding site. This interference disrupts the accurate translation of mRNA, leading to the production of non-functional proteins and ultimately bacterial cell death. The irreversible nature of the binding makes it particularly effective against susceptible bacteria. It does not undergo significant receptor binding, enzyme inhibition, or neurotransmitter modulation other than its ribosomal binding action.

Elimination Pathways: Primarily excreted unchanged through renal excretion by glomerular filtration.

Dosage

Standard Dosage

Adults:

• IV/IM: 15 mg/kg/day, given as a single daily dose or divided into 2-3 equal doses (e.g., 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours). The total daily dose should not exceed 1.5 g.

Children:

• IV/IM: 15-20 mg/kg/day, as a single dose or in 2 divided doses. For neonates, dosing is adjusted based on gestational age and postnatal age (see below).

Special Cases:

• Elderly Patients: Reduced doses or increased dosing intervals might be needed due to decreased creatinine clearance. Monitor serum creatinine levels closely.
• Patients with Renal Impairment: Dosage must be adjusted based on creatinine clearance or glomerular filtration rate (GFR). Various dosing nomograms and calculators are available to guide appropriate dosing adjustments in renal impairment. Therapeutic drug monitoring is crucial in these cases.
• Patients with Hepatic Dysfunction: No dosage adjustment is usually needed.
• Patients with Comorbid Conditions: Monitor closely for possible drug interactions.

Clinical Use Cases

Dosage recommendations can vary depending on the specific infection and clinical setting. Consult infectious disease specialists and pharmacists for optimal dosing strategies in specialized cases like severe sepsis, endocarditis, or febrile neutropenia. It is recommended to follow institution-specific guidelines or consult an infectious disease specialist for dosing in cases involving intubation, surgical procedures, mechanical ventilation, ICU use, or other emergency situations.

Dosage Adjustments:

Dosage needs to be adjusted in individuals with renal dysfunction. Use established guidelines or consult a nephrologist for guidance. Also, monitor patients for signs of toxicity. Adjust the dose based on patient response and serum drug levels.

Side Effects

Common Side Effects:

Nausea, vomiting, diarrhea, rash, pain or irritation at the injection site.

Rare but Serious Side Effects:

• Ototoxicity: Hearing loss (including deafness), tinnitus, vertigo, balance issues.
• Nephrotoxicity: Kidney damage, decreased urine output.
• Neuromuscular Blockade: Muscle weakness, respiratory paralysis.

Long-Term Effects: Prolonged use can increase the risk of ototoxicity and nephrotoxicity, especially in patients with pre-existing renal impairment.

Adverse Drug Reactions (ADR): Anaphylaxis (rare), severe allergic reactions, Stevens-Johnson Syndrome (very rare).

Contraindications

Hypersensitivity to amikacin or other aminoglycosides. Pre-existing hearing loss, vestibular dysfunction, or severe renal impairment. Myasthenia gravis.

Drug Interactions

Amikacin interacts with several other drugs, potentially increasing toxicity or decreasing efficacy. Notable interactions include:

• Other nephrotoxic or ototoxic drugs: (e.g., other aminoglycosides, vancomycin, amphotericin B, loop diuretics). Increased risk of kidney damage and hearing loss.
• Neuromuscular blocking agents: Enhanced neuromuscular blockade, potentially leading to respiratory paralysis.
• Cephalosporins: Increased nephrotoxicity.
• NSAIDs: Increased amikacin levels and toxicity.

Pregnancy and Breastfeeding

Amikacin is categorized as Pregnancy Category D. It can cross the placenta and cause fetal harm, including ototoxicity. Use only if the potential benefit to the mother outweighs the risk to the fetus. It is unknown if amikacin passes into breast milk. Caution is advised during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Inhibits protein synthesis by binding to the 30S ribosomal subunit of bacteria.
• Side Effects: Nausea, vomiting, ototoxicity, nephrotoxicity, neuromuscular blockade.
• Contraindications: Hypersensitivity to aminoglycosides, myasthenia gravis.
• Drug Interactions: Other aminoglycosides, vancomycin, loop diuretics, neuromuscular blocking agents.
• Pregnancy & Breastfeeding: Category D; use with caution.
• Dosage: Adult: 15mg/kg/day, divided into 2-3 doses. Pediatric: 15-20mg/kg/day. Adjustments required for renal dysfunction.
• Monitoring Parameters: Serum creatinine, BUN, peak and trough drug levels, audiometry, vestibular testing.

Popular Combinations

Amikacin may be used in combination with other antibiotics, such as beta-lactams or penicillins, for synergistic effects against specific infections like Pseudomonas aeruginosa. Specific combination regimens should be determined based on local antibiograms and infectious disease expertise.

Precautions

• General Precautions: Assess renal function before and during treatment. Monitor for signs of ototoxicity and nephrotoxicity.
• Specific Populations: See “Dosage” section for adjustments for renal impairment and older adults. Close monitoring of renal function and drug levels during pregnancy is crucial, if use is unavoidable. Exercise caution during breastfeeding.
• Lifestyle Considerations: Alcohol may potentiate nephrotoxicity.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Amikacin?

A: The recommended dosage for adults is 15 mg/kg/day, administered IM or IV, divided into 2-3 equal doses. For children, the dosage is 15-20 mg/kg/day. Dose adjustments are necessary for patients with renal impairment, elderly patients, and neonates.

Q2: What are the most serious side effects of Amikacin?

A: The most serious side effects are ototoxicity (hearing loss, tinnitus, vertigo) and nephrotoxicity (kidney damage). Neuromuscular blockade is also a rare but serious side effect.

Q3: How is Amikacin administered?

A: Administered intravenously (IV infusion over 30-60 minutes) or intramuscularly (IM).

Q4: What infections is Amikacin used to treat?

A: Amikacin is used to treat severe infections caused by susceptible Gram-negative bacteria, including Pseudomonas aeruginosa, E. coli, and others. It is also effective against some Gram-positive bacteria.

Q5: Can Amikacin be used during pregnancy?

A: Amikacin is a Pregnancy Category D drug and should be used during pregnancy only if the potential benefits outweigh the risks to the fetus. It can cross the placenta and cause fetal harm, including ototoxicity.

Q6: How does renal function affect Amikacin dosing?

A: Amikacin is primarily excreted unchanged by the kidneys. Renal impairment necessitates dosage adjustments to avoid toxicity. Dose reductions or increased dosing intervals are needed based on creatinine clearance or GFR. Therapeutic drug monitoring is crucial.

Q7: What are some key drug interactions with Amikacin?

A: Concomitant use of other nephrotoxic/ototoxic medications (e.g., vancomycin, other aminoglycosides, loop diuretics), and neuromuscular blocking agents should be avoided or carefully monitored.

Q8: How should Amikacin levels be monitored?

A: Both peak and trough levels are monitored during therapy. Peak levels are usually obtained one hour after the start of an IV infusion. Trough levels are measured just before the next dose. Therapeutic drug monitoring is crucial, especially in patients with renal impairment.

Q9: What are some signs of Amikacin toxicity?

A: Signs of toxicity include: tinnitus, vertigo, hearing loss (ototoxicity), decreased urine output, rising serum creatinine levels (nephrotoxicity), and muscle weakness (neuromuscular blockade).

Q10: What is the role of therapeutic drug monitoring with Amikacin?

A: Therapeutic drug monitoring helps optimize efficacy and minimize toxicity, especially in patients with renal insufficiency, elderly, and those receiving prolonged treatment. It involves measuring serum amikacin concentrations (peak and trough levels) and adjusting the dosage accordingly to achieve target therapeutic ranges.