indication

For short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species. Amikacin may also be used to treat Mycobacterium avium and Mycobacterium tuberculosis infections.

pharmacology

Amikacin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

mechanism of action

Aminoglycosides like Amikacin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Amikacin inhibits protein synthesis by binding to the 30S ribosomal subunit to prevent the formation of an initiation complex with messenger RNA. Specifically Amikacin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.

toxicity

Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity usually occurs several days following initiation of therapy. May cause irreversible ototoxicity. Otoxocity appears to be correlated to cumulative lifetime exposure. Drug accumulation in the endolymph and perilymph of the inner ear causes irreversible damage to hair cells of the cochlea or summit of ampullar cristae in the vestibular complex. High frequency hearing is lost first with progression leading to loss of low frequency hearing. Further toxicity may lead to retrograde degeneration of the 8th cranial (vestibulocochlear) nerve. Vestibular toxicity may cause vertigo, nausea, vomiting, dizziness and loss of balance.

absorption

Rapidly absorbed after intramuscular administration. Rapid absorption occurs from the peritoneum and pleura. Poor oral and topical absorption. Poorly absorbed from bladder irrigations and intrathecal administration.

half life

2-3 hours

route of elimination

Amikacin is excreted primarily by glomerular filtration.

drug interactions

Atracurium: The agent increases the effect of muscle relaxant

Bumetanide: Increased ototoxicity

Cefalotin: Increased risk of nephrotoxicity

Cefamandole: Increased risk of nephrotoxicity

Cefazolin: Increased risk of nephrotoxicity

Cefonicid: Increased risk of nephrotoxicity

Cefoperazone: Increased risk of nephrotoxicity

Ceforanide: Increased risk of nephrotoxicity

Cefotaxime: Increased risk of nephrotoxicity

Cefotetan: Increased risk of nephrotoxicity

Cefoxitin: Increased risk of nephrotoxicity

Cefradine: Increased risk of nephrotoxicity

Ceftazidime: Increased risk of nephrotoxicity

Ceftizoxime: Increased risk of nephrotoxicity

Ceftriaxone: Increased risk of nephrotoxicity

Cefuroxime: Increased risk of nephrotoxicity

Cephapirin: Increased risk of nephrotoxicity

Cisplatin: Increased risk of nephrotoxicity

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Due to the potential for additive or synergistic toxicities (including both nephrotoxicity and neuromuscular blockade) between colistimethate and the aminoglycoside antibiotics, this combination should be avoided whenever possible. If these agents must be used together, patients' renal and neuromuscular function should be monitored closely.

Doxacurium chloride: The agent increases the effect of muscle relaxant

Ethacrynic acid: Increased ototoxicity

Furosemide: Increased ototoxicity

Metocurine: The agent increases the effect of muscle relaxant

Mivacurium: The agent increases the effect of muscle relaxant

Pancuronium: The agent increases the effect of muscle relaxant

Pipecuronium: The agent increases the effect of muscle relaxant

Rocuronium: The agent increases the effect of muscle relaxant

Succinylcholine: The agent increases the effect of muscle relaxant

Tacrolimus: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Amikacin. Use caution during concomitant therapy.

Thalidomide: Thalidomide increases the renal toxicity of the aminoglycoside

Ticarcillin: Ticarcillin may reduce the serum concentration of Amikacin. Ticarcillin may inactivate Amikacin in vitro and the two agents should not be administered simultaneously through the same IV line.

Torasemide: Increased ototoxicity

Tubocurarine: The agent increases the effect of muscle relaxant

Vecuronium: The agent increases the effect of muscle relaxant