Amikin100 mg/2 ml

Amikin is an aminoglycoside antibiotic used for the short-term treatment of serious bacterial infections caused by susceptible gram-negative organisms, and as part of combination therapy for certain other infections.

Established/FDA-approved uses

• Septicemia (including neonatal sepsis)
• Serious lower respiratory tract infections caused by susceptible gram-negative organisms (e.g. Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia)
• Complicated and recurrent urinary tract infections
• Intra-abdominal infections, including peritonitis
• Skin, bone, and soft tissue infections, including those due to burns and post-operative infections
• Central nervous system infections (e.g. bacterial meningitis) caused by susceptible organisms, usually as adjunct therapy

Guideline-supported / combination uses

• Empiric therapy of suspected gram-negative sepsis, often combined with a beta-lactam antibiotic pending culture and susceptibility results
• As part of a multidrug regimen for multidrug-resistant tuberculosis (MDR-TB), used as a second-line injectable agent per WHO guidance when other options are unavailable or not tolerated
• Combined with a cell-wall-active agent (e.g. a penicillin) for synergy in selected serious infections such as enterococcal or streptococcal endocarditis

Amikin is not the drug of choice for infections caused by organisms susceptible to antibiotics with a narrower toxicity profile, and therapy should be guided by culture and susceptibility testing whenever possible.

Each mL of Amikacin injection contains Amikacin (as Amikacin sulfate) equivalent to 50 mg or 250 mg of Amikacin base, depending on strength/presentation. Formulations may also be supplied as a sterile powder for reconstitution. Please check the product label of the specific brand for exact strength and excipients.

Amikin is a semisynthetic aminoglycoside antibiotic derived from kanamycin. It is administered parenterally (by intramuscular or intravenous injection) and is used in hospital settings for the treatment of serious infections caused by susceptible gram-negative bacteria, and, in combination regimens, for certain other resistant infections including multidrug-resistant tuberculosis. Because of its narrow therapeutic index, Amikin therapy requires close clinical monitoring of renal function, hearing, and, where available, serum drug concentrations.

Amikin belongs to the aminoglycoside class of antibiotics.

Amikacin is a bactericidal aminoglycoside antibiotic. It acts by irreversibly binding to the 30S ribosomal subunit of susceptible bacteria, causing misreading of the genetic code and inhibition of protein synthesis, which leads to bacterial cell death. Amikacin is active against many aerobic gram-negative bacteria, including strains resistant to gentamicin and tobramycin, because it is relatively stable against many aminoglycoside-inactivating enzymes. It has limited activity against most gram-positive organisms and no useful activity against anaerobes.

Amikacin is poorly absorbed orally and is therefore given parenterally. It distributes mainly into extracellular fluid, achieves low cerebrospinal fluid penetration (increased with inflamed meninges), is not significantly metabolized, and is eliminated largely unchanged by glomerular filtration, with an elimination half-life of about 2-3 hours in patients with normal renal function.

Amikin is given only by a healthcare professional, either as a deep intramuscular injection or as an intravenous infusion diluted in an appropriate volume of a compatible solution (such as normal saline or 5% dextrose) and infused slowly over 30-60 minutes. It is not administered orally. Amikin should not be physically mixed in the same syringe or infusion with other drugs, particularly beta-lactam antibiotics, due to potential inactivation.

Amikin has clinically significant interactions with other drugs that share overlapping toxicities or affect neuromuscular function:

• Other nephrotoxic or ototoxic agents (e.g. other aminoglycosides, vancomycin, amphotericin B, cisplatin, cyclosporine): concurrent or sequential use increases the risk of kidney damage and hearing/balance damage; avoid combining unless clinically necessary and monitor closely.
• Potent diuretics (e.g. furosemide, ethacrynic acid), especially given intravenously: may enhance Amikin-associated ototoxicity, partly by altering antibiotic concentrations in serum and tissue.
• Neuromuscular blocking agents and general anesthetics: Amikin can potentiate neuromuscular blockade, increasing the risk of prolonged muscle weakness and respiratory depression/paralysis.
• Other beta-lactam antibiotics (in vitro): physical mixing in the same solution can inactivate Amikin; administer through separate lines or at separate times.

The most important adverse effects of Amikin are nephrotoxicity and ototoxicity; other effects are generally less common.

• Nephrotoxicity: Amikin can cause dose-related kidney damage, seen as rising blood urea nitrogen/creatinine, reduced urine output, or proteinuria; usually reversible on discontinuation but can be severe.
• Ototoxicity: both auditory (hearing loss, tinnitus) and vestibular (dizziness, vertigo, unsteadiness) toxicity can occur and may be irreversible; risk increases with higher doses, longer duration, pre-existing renal impairment, and concurrent ototoxic drugs.
• Neuromuscular blockade: rare but serious; can cause muscle weakness and respiratory paralysis, particularly with concurrent anesthetics/neuromuscular blockers or in myasthenia gravis.
• Other: injection site pain/irritation, rash, fever, headache, nausea, and, rarely, blood count changes or eosinophilia.

Pregnancy: Aminoglycosides such as Amikin can cross the placenta and there have been reports of total, irreversible, bilateral congenital deafness in children whose mothers received aminoglycoside antibiotics during pregnancy. Amikin should be used in pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus; consult a physician before use in pregnancy.

Lactation: It is not well established whether Amikin is excreted in human breast milk in clinically significant amounts; because of the potential for adverse effects in a nursing infant, Amikin should be used during breastfeeding only on medical advice, weighing the benefit of treatment against potential risk.

Amikin has a narrow therapeutic index and requires careful clinical supervision:

• Nephrotoxicity and ototoxicity: Monitor renal function (serum creatinine/BUN) and, where feasible, serum Amikin concentrations and hearing/vestibular function before and periodically during therapy, especially in patients with pre-existing renal impairment, the elderly, or those on prolonged courses.
• Neuromuscular blockade: Use with extreme caution in patients with neuromuscular disorders such as myasthenia gravis or Parkinsonism, as Amikin may aggravate muscle weakness and precipitate respiratory failure.
• Renal impairment: Dose and dosing interval must be adjusted; accumulation increases the risk of toxicity.
• Hydration: Ensure adequate hydration during therapy to reduce the risk of nephrotoxicity.
• Concurrent ototoxic/nephrotoxic drugs: See Interactions.

Antibiotic stewardship: Complete the full prescribed course of Amikin as directed by the treating physician; do not stop, extend, skip doses, or share this medicine with others without medical advice.

Overdose or excessive accumulation of Amikin can worsen nephrotoxicity, ototoxicity, and neuromuscular blockade, potentially leading to respiratory paralysis. If overdose is suspected, seek immediate medical attention or contact emergency services/poison control. Management is supportive under medical supervision and may include hemodialysis to help remove Amikin from the blood, particularly in patients with renal impairment; calcium salts may be considered by a physician to help reverse neuromuscular blockade. Do not attempt to manage a suspected overdose at home.

Store at room temperature (below 30°C), protected from light and moisture. Keep out of reach of children. Do not use if the solution is discolored or contains particulate matter. Unused diluted solutions should be discarded per institutional protocol.

Renal impairment: Dose and/or interval of Amikin must be reduced and, where available, serum concentrations monitored, because reduced clearance increases the risk of nephrotoxicity and ototoxicity.

Hepatic impairment: Amikin is not significantly metabolized by the liver, so specific hepatic dose adjustment is not established; standard dosing based on renal function generally applies.

Elderly: Age-related decline in renal function increases toxicity risk; renal function should be assessed and monitored, with dose adjusted accordingly.

Neonates and infants: Extracellular fluid volume and renal maturity vary with gestational and postnatal age; dosing must be individualized (see Pediatric Uses) and renal function and serum levels monitored where feasible.

Amikin is typically given for 7-10 days for most serious bacterial infections, based on clinical response and, where possible, culture results; treatment beyond 10 days is generally avoided due to increasing risk of toxicity unless closely monitored. For multidrug-resistant tuberculosis, Amikin is used for a longer duration as part of a combination regimen under specialist supervision, per national TB program guidelines. The exact duration should be determined and periodically reviewed by the treating physician.

Where Amikin is supplied as a sterile powder for injection, it should be reconstituted with an appropriate volume of Sterile Water for Injection as directed on the product label to achieve the labeled concentration, then further diluted in 100-200 mL of a compatible intravenous fluid (such as 0.9% sodium chloride or 5% dextrose in water) for intravenous infusion. Reconstitution and dilution should be performed by a healthcare professional using aseptic technique; the resulting solution should be inspected visually for particulate matter and discoloration before use, and used within the time period specified by the manufacturer.

Aminoglycoside antibiotics

Amikacin binds irreversibly to the 30S ribosomal subunit of susceptible bacteria, interfering with the initiation of protein synthesis and causing misreading of messenger RNA. This leads to production of nonfunctional or toxic proteins and disruption of the bacterial cell membrane, resulting in a bactericidal (cell-killing) effect against susceptible aerobic gram-negative organisms.

D

Amikin is used in infants and children, including neonates, for serious gram-negative infections and sepsis, with dosing individualized on a mg/kg basis according to age, gestational age (in neonates), and weight. Safety and efficacy for indications outside standard serious bacterial infections have not been established in children, and use should be under specialist/pediatric supervision with monitoring of renal function and, where feasible, hearing and serum drug concentrations, given the risk of nephrotoxicity and ototoxicity in this population.