Download COLIRACIN INJECTION Composition Each vial contains: Colistin

COLIRACIN INJECTION
Composition
Each vial contains:
Colistin sulfomethate sodium 1 million units
Action
Colistin sulfomethate exhibits bactericidal activity against Gram-negative bacilli such as
Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Indications
Treatment of acute and chronic urinary tract infections due to colistin-sensitive strains of Gramnegative bacilli such as those found in pyelitis, pyelocystitis and urethritis.
Treatment of wound and burn infections caused by sensitive microorganisms.
Treatment of septicemia, especially when caused by Pseudomonas aeruginosa.
Contraindications
Patients with a history of sensitivity to this drug or to other polymyxins.
Warnings
Transient neurological disturbances may occur. These include circumoral paresthesias or
numbness, tingling or formication of the extremities, generalized pruritus, vertigo, dizziness and
slurring of speech.
Renal function should be monitored since adverse renal effects may occur, regardless of dosage. A
diminished urine output or increased concentrations of blood urea nitrogen (BUN) or serum
creatinine necessitate immediate discontinuation of the drug.
Prolonged use may result in overgrowth of non-susceptible organisms. If superinfection occurs,
appropriate therapy should be initiated immediately.
Use in Pregnancy
Safety of use during pregnancy has not been established. Therefore, the drug should only be used
when the potential benefits to the mother justify the possible risks to the fetus. Caution should also
be exercised in women of childbearing age who may become pregnant. Colomycin is secreted in
breast milk and patients to whom the drug is administered should not breast-feed an infant.
Adverse Reactions
Respiratory arrest, paresthesia, tingling of the extremities and/or of the tongue, and generalized
itching or urticaria have been reported.
Drug fever, dizziness, vertigo, giddiness, ataxia, blurred vision and slurring of speech may occur.
Other neurotoxic effects, including mental confusion, coma, psychosis and seizures have also been
reported, especially in patients receiving high dosage or in patients with renal impairment.
Gastrointestinal upset may occur.
Although a causal relationship has not been definitely established, leukopenia, granulocytopenia
and hepatotoxicity have been reported rarely.
Bronchospasm may occur on antibiotic inhalation; this may be treated with beta2-agonists.
Precautions
Since transient neurological disturbances may occur, patients should be warned that their ability to
perform potentially-hazardous tasks requiring mental alertness or physical coordination, such as
driving a vehicle or operating machinery, may be impaired.
Administration of Coliracin in excess of renal excretory capacity will lead to high serum levels and
can result in impairment of renal function. If not recognized, this can lead to acute renal
insufficiency, renal shutdown and further concentration of the antibiotic in the body. At this point,
interference of nerve transmission at neuromuscular junctions may occur and result in muscle
weakness and apnea.
Coliracin should be used with caution in the presence of impaired renal function. The decline in
renal function with advanced age must also be taken into consideration. In the presence of signs
indicating the development of impaired renal function, therapy should be discontinued. However, if
a life-threatening situation exists, therapy may be reinstituted at a lower dosage, but only when the
infection is caused by pathogens resistant to other, less toxic antibiotics.
A decrease in urine output or increase in BUN or serum creatinine can be interpreted as signs of
nephrotoxicity.
Nephrotoxicity manifested as decreased urine output, increased BUN and serum creatinine,
proteinuria, hematuria and casts in the urine has also been reported in patients receiving usual doses
of colistin sulfomethate, and was not necessarily preceded by renal impairment.
Drug Interactions
Coliracin/Other Antibacterial Agents/Methoxyflurane
Kanamycin, streptomycin, dihydrostreptomycin, polymyxin B and neomycin have been reported to
interfere with nerve transmission at the neuromuscular junction and should not be administered
concomitantly with Coliracin. Concomitant administration of Coliracin with aminoglycosides,
amphotericin B, capreomycin, polymyxin B sulfate, vancomycin and methoxyflurane should be
avoided, due to potentially additive nephrotoxic and/or neurotoxic effects.
It has been reported that concomitant cephalothin administration has been associated with an
increase in the incidence of renal toxicity.
Coliracin/Curariform Muscle Relaxants
Curariform muscle relaxants should be used with extreme caution in patients receiving Coliracin,
since their action interferes with nerve transmission. If apnea occurs, it may be treated with assisted
respiration, oxygen and calcium chloride injection.
Dosage and Administration
Coliracin injection is usually administered IM or IV, but, when indicated, may also be introduced
via local vaginal irrigation.
The recommended dosage in children and adults up to 60kg is 50,000 units/kg body weight over 24
hours, divided into three 8-hourly doses. Serum levels should be measured if used in the newborn.
The recommended dosage in adults over 60kg body weight is 6 million units over 24 hours (i.e. 2
vials every 8 hours).
IV Administration:
Direct intermittent administration- slowly inject one third of daily dose over a period of 3-5
minutes every 8 hours.
Continuous intravenous infusion- When administering Coliracin by continuous intravenous
infusion, the total daily dosage remains the same divided into three 8-hourly doses. It is preferable
to complete infusions within 6 hours.
The above recommendations represent average dosages. Should the clinical or bacteriological
response be slow, the dosage may be increased, as indicated by the patient's condition.
A minimum of 5 days of treatment is recommended.
Impaired Renal Function
Dosage adjustment based on creatinine clearance (Ccr) and BUN is recommended when treating
patients with impaired renal function, as follows:
™ Ccr between 20-72ml/min
BUN>60mg/100ml (>10nmol/l)
Adult dosage - 1.5-2 million units every 8 hours
Pediatric dosage - 12500-16000 units/kg every 8 hours
™ Ccr between 10-20ml/min
BUN>100 mg/100ml (>16.5nmol/l)
Adult dosage - 1.5 million units every 12-18 hours
Pediatric dosage - 12500 units/kg every 12-18 hours
™ Ccr less than 10ml/min
BUN>200mg/100ml (>33 nmol/l)
Adult dosage - 1 million units every 18-24 hours
Pediatric dosage - 8000 units/kg every 18-24 hours
It is important to stress that adjustments may still have to be made upon evaluation of the individual
patient. Blood level determinations are recommended: 10-15mcg/ml should be adequate.
Overdosage
Overdosage can result in renal insufficiency, muscle weakness and apnea. A decrease in urine
output or increase in BUN or serum creatinine can be interpreted as signs of nephrotoxicity. These
manifestations are reversible following discontinuation of the antibiotic. There is no specific
antidote. Management is by supportive treatment and measures to increase the rate of elimination
of colistin e.g. mannitol diuresis, prolonged haemodialysis or peritoneal dialysis.
Pharmaceutical Precautions
Unopened vials of Coliracin injection are stable until the date indicated when stored below 25ºC,
protected from light
Before use, the vial should be reconstituted with at least 2.00 ml sterile water for injection.
During reconstitution swirl gently to avoid frothing. Wait a few minutes until dissolution is
completed.
Parenteral products should be inspected visually for particles and discoloration prior to
administration. Coliracin solution should not be used if it contains a precipitate or is discolored.
Compatible infusion solutions are normal saline, 5% Dextrose, 5% Fructose, Ringer's solution and
10% Dextran-40 in normal saline.
Solutions of Coliracin for parenteral administration should preferably be freshly prepared.
Mixed infusions or injections containing Coliracin should be avoided.
1mg colistin sulfomethate sodium provides approximately 12,500 units.
Presentation
Vials of 1 million units.
Reg. No. 119 27 22678 00
Manufacturer:
Rafa Laboratories Ltd, Israel, Tel:02-5893939, Fax:02-5870282, [email protected]
The format and content of this document have been approved by the Ministry of Health in June 2005