PERK

TECHNICAL LITERATURE

LogoAMCIL-A

100M,g/250mg/500mg Injection (I.M. & I.V. use)

AMCIL-A (Amikacin injection 100mg/2mL; 250mg/2mL; 500mg/2mL)

Description

AMCIL-A (Amikacin) is a semisynthetic aminoglycoside antibiotic derived from kanamycin. Amikacin occurs as a white, crystalline powder and is sparingly soluble in water. The injection consists of the sulphate salt. The molecular formula is C22H47N5O21S2 .

AMCIL-A Injection is a sterile clear, colourless solution, free from specks, lint, or other visible evidence of contamination. Each 2 mL vial contains amikacin sulphate equivalent to amikacin activity 100/250/500 mg (1/2.5/5 x 100,000 I.U.). The vial also contains Sodium Citrate I.P. and Sodium Metabisulfite I.P and suitable preservatives.

Pharmacology

Microbiology

AMCIL-A is active, in vitro, against the following organisms: (all strength calculated on basis of 500mg inj.)

Gram-negative

MIC microgram/mL

Pseudomonas species

1.6 - 12.5

Proteus species (indole-positive and indole negative)

1.6 - 3.1

Klebsiella pneumoniae

1.6 - 3.1

Enterobacter cloacae

1.6 - 3.1

Serratia species

0.8 - 3.1

Acinetobacter

No information available

Providencia stuartii

3.1

Citrobacter freundii

1 - 8

Escherichia coli

1.6 - 3.1

Gram-positive

 

Staphylococcus species
(penicillinase and nonpenicillinase producing,
including methicillin resistant strains)

0.4 - 5.0


(AMCIL-A) Amikacin’s structure has been altered to reduce the possible route of enzymatic deactivation, thus reducing bacterial resistance. Many strains of Gram-negative organisms resistant to gentamicin and tobramycin have shown to be sensitive to amikacin in vitro.

Pharmacokinetics

Absorption

Following IM administration of a single dose of AMCIL-A of 7.5 mg/kg in adults with normal renal function, peak plasma amikacin concentrations of 17-25 micrograms/mL are attained within 45 minutes to 2 hours.

Following IV infusion of the same dose given over 1 hour peak plasma concentrations of the drug average 38 micrograms/mL immediately following the infusion, 5.5 micrograms/mL at 4 hours, and 1.3 micrograms/mL at 8 hours.

Distribution

Following administration of usual dosages of AMCIL-A, amikacin has been found in bone, heart, gallbladder, and lung tissue. Amikacin is also distributed into bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids.

Elimination

The plasma elimination half-life of AMCIL-A is usually 2-3 hours in adults with normal renal function and is reported to range from 30-86 hours in adults with severe renal impairment.

In adults with normal renal function, 94-98% of a single IM or IV dose of AMCIL-A is excreted unchanged by glomerular filtration within 24 hours. The drug may be completely recovered within approximately 10-20 days in patients with normal renal function. Terminal elimination half-lives of greater than 100 hours have been reported in adults with normal renal function following repeated IM or IV administration of the drug.

In patients with impaired renal function, the clearance of amikacin is decreased; the more severe the impairment, the slower the clearance. Therefore, the interval between doses should be adjusted according to the degree of renal impairment. Endogenous creatinine clearance rate and serum creatinine which have high correlation with serum half-life of amikacin, may be used as a guide for this purpose (see Dosage and Administration - Impaired Renal Function).

Indications

AMCIL-A Injection is indicated in the short-term treatment of serious infections caused by susceptible strains of Gram-negative bacteria, (see Microbiology).

Staphylococcus aureus, including methicillin-resistant strains is the principal Gram-positive organism sensitive to amikacin.

The use of amikacin in the treatment of staphylococcal infections should be restricted to second-line therapy, and should be confined to patients suffering from severe infections caused by susceptible strains of stapylococcus who have failed to respond or are allergic to other available antibiotics.

AMCIL-A Injection is indicated in the treatment of neonatal sepsis when sensitivity testing indicates that other aminoglycosides cannot be used.

In certain severe infections such as neonatal sepsis, concomitant therapy with a penicillin type drug may be indicated because of the possibility of infections due to Gram-positive organisms such as streptococci or pneumococci. If concomitant treatment with a penicillin type drug is indicated, then the drugs should be administered separately and at different sites because in-vitro mixing of the two drugs causes inactivation of AMCIL-A.

Clinical studies have shown AMCIL-A to be effective in treating bacteraemia, septicaemia including neonatal sepsis and serious infections of the respiratory tract, bones and joints, central nervous system, skin and skin structures (including those resulting from burns), intra-abdominal organs, post-operative infections and complicated and recurrent urinary tract infections, when caused by susceptible organisms.

Contraindications

AMCIL-A Injection is contraindicated in patients with a known history of hypersensitivity to amikacin, any constituents of the injection (see Description ) or in patients who may have subclinical renal or eighth nerve damage induced by prior administration of nephrotoxic and/or ototoxic agents, as the toxicity may possibly be additive.

Pregnancy (see Use in Pregnancy) ; Lactation (see, Use in Lactation).

Warnings and Precautions

Treatment with amikacin for more than 10 days has not been established as being safe. Patients undergoing treatment with parenteral aminoglycosides should be under close clinical observation and evaluation because of the potential ototoxicity and nephrotoxicity associated with their use.

Use in Pregnancy

Category D. Gentamicin and other aminoglycosides cross the placenta. There is evidence of selective uptake of gentamicin by the foetal kidney resulting in damage (probably reversible) to immature nephrons. Eighth cranial nerve damage has also been reported following in-utero exposure to some of the aminoglycosides. Because of the chemical similarity, all aminoglycosides must be considered potentially nephrotoxic and ototoxic to the foetus. It should also be noted that therapeutic blood levels in the mother do not equate with safety for the foetus.

Use in Lactation

It is not known whether amikacin is excreted in breast milk. Since the possible harmful effect on the infant is not known, it is recommended that if nursing mothers must be given amikacin, the infants should not be breast fed during therapy.

Compatibilities

Amikacin sulphate is stable for 24 hours at room temperature in the presence of light at 5 mg/mL and 0.25 mg/mL in 0.9% Sodium Chloride Intravenous Infusion B.P. and 5% Glucose Intravenous Infusion B.P. solutions.

Incompatibilities

Amikacin Injection may be prescribed as concurrent therapy with other antibacterial agents in mixed or superinfections. In such situations, Amikacin Injection should never be physically mixed with other antibacterial agents in infusion bags, syringes or any other container equipment. Each agent should be administered separately and at different sites following the manufacturer's recommended route.

Adverse Reactions

Amikacin induced hepatotoxicity is not a common side effect, however it may occur. Increased serum transaminases (ALT, AST) increased serum bilirubin, hepatomegaly, and hepatic necrosis have been reported.

The percentages below refer to incidence in clinical trials.

More common reactions

Auditory and Vestibular:

Hearing loss (4%) (permanent in some cases)
Hearing loss is usually manifested initially by diminution of high-tone acuity.

Biochemical abnormalities:

Increased serum urea, decreased creatinine clearance, elevated serum creatinine, azotaemia.

Genitourinary:

Reduced renal function, oliguria

Injection site reactions:

Pain at site of intramuscular injection (6%).

 Dosage and Administration

Uncomplicated infections due to sensitive organisms should respond to treatment within 24 to 48 hours at the recommended dosage. If no improvement occurs within three to five days, the use of amikacin sulphate should be re-evaluated and consideration be given to alternative therapy. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage.

Whenever possible, and especially in patients with impaired renal function, peak and trough amikacin serum concentrations should be determined and dosage adjusted where necessary to maintain desired serum concentrations. In general, desired peak concentrations are between 15 to 30 micrograms/mL, and trough concentrations should not exceed 5 to 10 micrograms/mL. An increased risk of toxicity may be associated with prolonged peak amikacin serum concentrations greater than 30 to 35 micrograms/mL.

Intramuscular or Intravenous Administration

The intramuscular route is preferred for most infections, but in life-threatening infections or when an intramuscular injection is not feasible, an intravenous infusion (0.25% over 30 to 60 minutes) may be used.

The compatible diluents for intravenous use if required are as follows: 5% Glucose Intravenous Infusion B.P. in Water for Injections B.P. and Sodium Chloride Intravenous Infusion B.P. (0.9%). Use solutions for I.V. administration within 12 hours after preparation.

Dosage

Dosage of AMCIL-A (amikacin sulphate) is expressed in terms of amikacin and calculated on a body weight basis. Dosage is identical for both routes of administration.

Adults and Children:

The usual recommended dose of AMCIL-A (amikacin) is 15mg/kg daily given in two or three equally divided doses.

Neonates and Premature Infants:

Dosage given for patients with normal renal function. Initiate treatment with a loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours. The maximum total daily dose should not exceed 15 mg/kg. Solution infusions via the I.V. route should be given over a 1 to 2 hour period.

Insufficient clinical use has not enabled firm dosage guidelines to be established for the use of amikacin in premature infants.

Elderly:

Amikacin is excreted by the renal route. Since renal function could be failing in the elderly, it should be assessed whenever possible and the dosage adjusted accordingly, if necessary. Refer to "Impaired renal function" of dosage description.

Urinary Tract Infections (other than pseudomonal infections):

500 mg/day in two equally divided doses is recommended.

Impaired Renal Function:

In patients with impaired renal function, either the dose or the dosage interval needs to be adjusted to avoid accumulation. The dosage interval may be calculated using the following formula:

Serum creatinine concentration (mg / 100 mL) x 9 = dosage interval (hours)

Overdosage

Management

In the event of overdosage or toxic reactions peritoneal dialysis or haemodialysis should be considered. These procedures are of particular importance in patients with impaired renal function. In the newborn infant, exchange transfusion may also be considered.

Clinical features

Likely signs and symptoms include tinnitus, vertigo, reversible or irreversible deafness, skin rash, drug fever, headache, paraesthesia, reduced renal function or renal failure.

Medicine Classification

Prescription Only Medicine

Storage

Store below 25°C.

Presentation

Strength / Pack Size

100 mg (100,000 I.U.)/2mL 100 x 2 mL vials

250 mg (250,000 I.U.)/2mL 100 x 2 mL vials

500 mg (500,000 I.U.)/2mL 100x 2 mL vials

Date of Preparation

1 August 2005

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