Dosing and uses of Amikin (amikacin)
Adult dosage forms and strengths
injectable solution
- 50mg/mL
- 250mg/mL
General Dosing
15 mg/kg/day divided IV/IM q8-12hr
Urinary Tract Infection
250 mg IV/IM q12hr
Extended Interval Dosing (q24 Hours)
First dose: 15 mg/kg IV based on lean body weight
Subsequent doses: consult pharmacist
Hospital Acquired Pneumonia
20 mg/kg/day IV; may administer with antipseudomonal beta-lactam or carbapenem
Dosage modifications
Renal impairment
- CrCl >90 mL/min and aged <60 yr: q8hr
- CrCl 60-90 mL/min OR aged ≥60 yr: q12hr
- CrCl 25-60 mL/min: q24hr
- CrCl 10-25 mL/min: q48hr
- CrCl <10 mL/min: q72hr
- Administer after dialysis in ESRD
Dosing Considerations
Monitor: peak, trough, renal & auditory function
Peak 15-40 mg/L, trough 5-10 mg/L
Mycobacterium Infections (Orphan)
Inhaled liposomal amikacin (Arikayce)
Orphan designation for treatment infections caused by nontuberculous mycobacteria
Sponsor
- Insmed Incorporated; Princeton Corporate Plaza IV, Suite C; Monmouth Junction, NJ 08852-1919
Pseudomonas aeruginosa Lung Infections (Orphan)
Orphan designation for management of P aeruginosa lung infections in patients with cystic fibrosis
Sponsor
- PlumeStars s.r.l.; Via Lago Scuro 11; 43124 Parma; Italy
Bronchopulmonary Pseudomonas aeruginosa (Orphan)
Inhaled liposomal amikacin (Arikayce)
Orphan designation for treatment of broncophulmonary P aeurginosa infections in cystic fibrosis
Administration: Inhalation NOTE: FDA imposed clinical hold on trials on August 1, 2011
Sponsor
- Insemed Inc; 11 Deer Park Drive, Suite 117; Monmouth Junction, NJ 08852
Bronchiectasis (Orphan)
Inhaled liposomal amikacin (Arikayce)
Orphan designation for treatment of bronchiectasis in patients with P aeurginosa infections or other susceptible microbial pathogens (eg, NTM)
Administration: Inhalation NOTE: FDA imposed clinical hold on trials on August 1, 2011
Sponsor
- Insemed Inc; 11 Deer Park Drive, Suite 117; Monmouth Junction, NJ 08852
Non-tuberculous Mycobacteria Infections (Orphan)
Encochleated amikacin product
Orphan designation for non-tuberculous mycobacteria (NTM) infections
Sponsor
- Aquarius Biotechnologies, Inc; 1545 U.S. 206; Bedminster Township, New Jersey 07921
Pediatric dosage forms and strengths
injectable solution
- 50mg/mL
- 250mg/mL
General Dosing
15-22.5 mg/kg/day IV/IM divided q8hr
Neonates
Aged ≤7 days
- ≤29 weeks gestational age: 18 mg/kg IV/IM q48hr
- 30-33 weeks gestational age: 18 mg/kg IV/IM q36hr
- ≥34 weeks gestational age: 15 mg/kg IV/IM q24hr
Aged >7 days
- 30-33 weeks gestational age: 15 mg/kg IV/IM q24hr
- ≥34 weeks gestational age: 15 mg/kg IV/IM q12-18hr
Aged 8-28 days old & <29 weeks gestational age
- 15 mg/kg IV/IM q36hr
- Also use this dose for the following: significant asphyxia, indomethacin for PDA, poor cardiac output, or renal impairment
Neonates Aged >28 days old & <29 weeks gestational age
- 15 mg/kg IV/IM q24hr
- Also use this dose for the following: significant asphyxia, indomethacin for PDA, poor cardiac output, or renal impairmen
Amikin (amikacin) adverse (side) effects
1-10%
Neurotoxicity
Nephrotoxicity (if trough >10 mg/L)
Ototoxicity
<1%
Hypotension
Headache
Drug fever
Rash
Nausea
Vomiting
Eosinophilia
Paresthesia
Tremor
Arthralgia
Weakness
Allergic reaction
Warnings
Black box warnings
Neurotoxicity, manifested as both bilateral auditory and vestibular ototoxicity, can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended. High-frequency deafness usually occurs first and can be detected only by audiometric testing
Vertigo may occur and may be evidence of vestibular injury
Aminoglycosides are potentially nephrotoxic
Risk is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy. Rarely, nephrotoxicity may not become apparent until the first few days after cessation of therapy
Use with caution in premature infants and neonates because of renal immaturity and the resulting prolongation of serum half-life of the drug
Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and oral use of aminoglycosides, especially when given soon after anesthesia or muscle relaxants
If blockage occurs, calcium salts may reverse these phenomena, but mechanical respiratory assistance may be necessary
Avoid concurrent or sequential use of neurotoxic and/or nephrotoxic drugs including other aminoglycosides (eg, amikacin, streptomycin, neomycin, kanamycin, gentamicin, paromomycin
Cumulative listing of drugs to avoid from all aminoglycoside package inserts include amphotericin B, bacitracin, cephaloridine, cisplatin, colistin, polymyxin B, vancomycin, and viomycin
Avoid potent diuretics (eg, ethacrynic acid, furosemide) because they increase risk of ototoxicity
When administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue
Contraindications
Documented hypersensitivity
Cautions
Renal impairment
Risk of neurotoxicity, ototoxicity, nephrotoxicity - risk of ototoxicity increase with concurrent loop diuretics
Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission
Pregnancy and lactation
Pregnancy category: d
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Amikin (amikacin)
Mechanism of action
Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition. For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin
Absorption
IM absorption: May be delayed in bedridden patient
Peak plasma time, IM: 45-120 min
Distribution
Protein bound: 0-11%
Vd: 0.25-0.4 L/kg, primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed; crosses placenta, relative diffusion of antimicrobial agents from blood into CSF: good only with inflammation (exceeds usual MICs)
Elimination
Half-Life: 2-3 hr (normal renal function)
Excretion: urine (94-98%)
Dialyzable: HD: yes; PD: yes
Administration
IV Incompatibilities
Additive: aminophylline in dextrose-containing diluents, amphotericin B, ampicillin, cefazolin, cefotaxime(?), ceftazidime, chloramphenicol, chlorothiazide, heparin, phenytoin, thiopental, vitamin B/C
Syringe: heparin
Y-site: allopurinol, amphotericin B cholesteryl sulfate, azithromycin, hetastarch, propofoL
IV Compatibilities
Solution: compatible with most common solvents
Additive (partial list): aminophylline (in LR, NS, Ringer's, Na-Lactate 1/6M), ascorbic acid, CaCl2, cefepime, ceftriaxone, ciprofloxacin, clindamycin, dexamethasone Na-phosphate(? may be conc-dep), diphenhydramine, fluconazole, furosemide, metronidazole, prochlorperazine, promethazine, NaHCO3, KCl (may not be in dextran6%/NS), succinylcholine, vancomycin
Syringe: caffeine, clindamycin, doxapram
Y-site (partial list): acyclovir, amiodarone, diltiazem, enalaprilat, fluconazole, furosemide, levofloxacin, linezolid, lorazepam, MgSO4, midazolam, milrinone, morphine, ondansetron, warfarin, zidovudine
IV Preparation
Dilute 500 mg to 100 or 200 mL sterile diluent (0.9% NaCl or D5W)
IV/IM Administration
IM: Administer undiluted to upper outer quadrant of buttocks
IV: Infuse over 30-60 min in adults and children; infuse over 1-2 hr in infants
