Elsaad products
Member Login


New Products
Newsletter
 
 
Our Products
 
Product Name
:
KAMICINE
Chemical Name
:
Amikacin (Sulfate)
Therapeutic Category
:
Antimicrobial
Pharmacologic Category
:
Antibiotic, Aminoglycoside
Pharmaceutical Form
:
Ampoule
Composition
:
Amikacin (Sulfate) 100mg / 500mg
Dosing
 
Dosing: Adult
Individualization is critical because of the low therapeutic index
Note: Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.
Usual dosage range:
I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours; Note: Some clinicians suggest a daily dose of 15-20 mg/kg for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.
Intrathecal/intraventricular (unlabeled route): Meningitis (susceptible gram-negative organisms): 5-50 mg/day
Indication-specific dosing:
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin
Hospital-acquired pneumonia (HAP): I.V.: 20 mg/kg/day with antipseudomonal beta-lactam or carbapenem (American Thoracic Society/ATS guidelines)
Meningitis (susceptible gram-negative organisms):
I.V.: 5 mg/kg every 8 hours (administered with another bacteriocidal drug)
Intrathecal/intraventricular (unlabeled route): Usual dose: 30 mg/day (IDSA, 2004); Range: 5-50 mg/day (with concurrent systemic antimicrobial therapy) (Gilbert, 1986; Guardado, 2008; IDSA, 2004; Kasiakou, 2005)
Mycobacterium fortuitum, M. chelonae, or M. abscessus: I.V.: 10-15 mg/kg daily for at least 2 weeks with high dose cefoxitin

Dosing: Pediatric

Usual dosage range: Infants and Children: I.M., I.V.: 5-7.5 mg/kg/dose every 8 hours
Note: Individualization is critical because of the low therapeutic index
Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total body weight (TBW)
In morbid obesity, dosage requirement may best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW)
Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients).
Clcr ≥60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr <20 mL/minute: Loading dose, then monitor levels
Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (20%; variable; dependent on filter, duration, and type of HD): 5-7.5 mg/kg every 48-72 hours. Follow levels. Redose when pre-HD concentration <10 mg/L; redose when post-HD concentration <6-8 mg/L (Heintz, 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): Dose as Clcr <20 mL/minute: Follow levels.
Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
CVVH/CVVHD/CVVHDF: Loading dose of 10 mg/kg followed by maintenance dose of 7.5 mg/kg every 24-48 hours
Note: For severe gram-negative rod infections, target peak concentration of 15-30 mg/L; redose when concentration <10 mg/L (Heintz, 2009).
Use
 
Treatment of serious infections (bone infections, respiratory tract infections, endocarditis, and septicemia) due to organisms resistant to gentamicin and tobramycin, including Pseudomonas, Proteus, Serratia, and other gram-negative bacilli; documented infection of mycobacterial organisms susceptible to amikacin
Use - Unlabeled/Investigational
Bacterial endophthalmitis
Adverse Reactions
 
1% to 10%:
Central nervous system: Neurotoxicity
Otic: Ototoxicity (auditory), ototoxicity (vestibular)
Renal: Nephrotoxicity
<1% (Limited to important or life-threatening): Allergic reaction, dyspnea, eosinophilia
Contraindications
 
Hypersensitivity to amikacin sulfate or any component of the formulation; cross-sensitivity may exist with other aminoglycosides
Warnings / Precautions Drug
 
Boxed Warnings:
• Nephrotoxicity: See “Concerns related to adverse effects” below.
• Neuromuscular blockade and respiratory paralysis: See “Concerns related to adverse effects” below.
• Neurotoxicity: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; usual risk factors include pre-existing renal impairment, concomitant nephrotoxic medications, advanced age and dehydration. Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible.
• Neuromuscular blockade and respiratory paralysis: [U.S. Boxed Warning]: May cause neuromuscular blockade and respiratory paralysis; especially when given soon after anesthesia or muscle relaxants.
• Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity; usual risk factors include pre-existing renal impairment, concomitant neuro-/nephrotoxic medications, advanced age and dehydration. Ototoxicity is proportional to the amount of drug given and the duration of treatment. Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage. Discontinue treatment if signs of ototoxicity occur.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hearing impairment: Use with caution in patients with pre-existing vertigo, tinnitus, or hearing loss.
• Hypocalcemia: Use with caution in patients with hypocalcemia.
• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.
• Renal impairment: Use with caution in patients with pre-existing renal insufficiency; dosage modification required.
Dosage form specific issues:
• Sulfite: Solution contains sodium metabisulfate; use caution in patients with sulfite allergy.
Interactions
 
AbobotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of AbobotulinumtoxinA. Risk C: Monitor therapy
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Risk D: Consider therapy modification
CycloSPORINE: Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy
Gallium Nitrate: Aminoglycosides may enhance the nephrotoxic effect of Gallium Nitrate. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
OnabotulinumtoxinA: Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Cloxacillin; Dicloxacillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Potassium. Risk D: Consider therapy modification
RimabotulinumtoxinB: Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Pregnancy
 
D
Pregnancy Implications
Adverse events were not observed in the initial animal reproduction studies; however, renal toxicity has been reported in additional studies. Amikacin crosses the placenta, produces detectable serum levels in the fetus, and concentrates in the fetal kidneys. Because of several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy, the manufacturer classifies amikacin as Pregnancy Risk Factor D. Although serious side effects to the fetus have not been reported following maternal use of amikacin, a potential for harm exists.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of amikacin may be altered. Pregnant women have an average-to-larger volume of distribution which may result in lower peak serum levels than for the same dose in nonpregnant women. Serum half-life may also be shorter.
Lactation
 
Enters breast milk/not recommended
Breast-Feeding Considerations
Amikacin is excreted into breast milk in trace amounts; however, it is not absorbed when taken orally. This limited oral absorption may minimize exposure to the nursing infant. Nondose-related effects could include modification of bowel flora. Breast-feeding is not recommended by the manufacturer.
Monitoring Parameters
 
Urinalysis, BUN, serum creatinine, appropriately timed peak and trough concentrations, vital signs, temperature, weight, I & O, hearing parameters
Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.
Reference Range
Sample size: 0.5-2 mL blood (red top tube) or 0.1-1 mL serum (separated)
Therapeutic levels:
Peak:
Life-threatening infections: 25-40 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL
Trough: <8 mcg/mL
The American Thoracic Society (ATS) recommends trough levels of <4-5 mcg/mL for patients with hospital-acquired pneumonia.
Toxic concentration: Peak: >40 mcg/mL; Trough: >10 mcg/mL
Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose
Mechanism of Action
 
Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits
Pharmacodynamics / Kinetics
 
Absorption:
I.M.: Rapid
Oral: Poorly absorbed
Distribution: Vd: 0.25 L/kg; primarily into extracellular fluid (highly hydrophilic); penetrates blood-brain barrier when meninges inflamed
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Normal meninges: 10% to 20%; Inflamed meninges: 15% to 24%
Protein-binding: 0% to 11%
Half-life elimination (renal function and age dependent):
Infants: Low birth weight (1-3 days): 7-9 hours; Full-term >7 days: 4-5 hours
Children: 1.6-2.5 hours
Adults: Normal renal function: 1.4-2.3 hours; Anuria/end-stage renal disease: 28-86 hours
Time to peak, serum: I.M.: 45-120 minutes
Excretion: Urine (94% to 98%)
 
   
 
Powered by: TSS-EST.COM