Posology : מינונים

4.2    Posology and method of administration

Coliracin injection is usually administered IM or IV.
Coliracin must be reconstituted before use.
Dosage
The dose and the treatment duration are determined by the severity and type of infection and the age, weight and renal function of the patient as well as the clinical response. Should clinical or bacteriological response be slow, the dose may be increased as indicated by the patient's condition.
A minimum of 5 days treatment is generally recommended. For the treatment of respiratory exacerbations in cystic fibrosis patients, treatment should be continued for up to 12 days.

The recommended dosage in children and adults up to 60kg is 50,000 units/kg/day to maximum of 75,000 units/kg/day. The total daily dose should be divided into three doses given at approximately 8-hour intervals. Serum levels should be measured if used in the newborn.
The recommended dosage in patients over 60 kg: 1-2 million units three times a day. The maximum dose is 6 million units in 24 hours.
Dosage should be in line with relevant treatment guidelines. Limited pharmacokinetic data from critically ill patients suggest that use of a loading dose and higher than standard doses may be appropriate. For severe infections and in critically ill patients doses up to 9 million IU per day in divided doses, have been reported in the literature. Clinical efficacy and safety data with these regimens are very limited and caution is advised .

Anomalous distribution in patients with cystic fibrosis may require higher doses in order to maintain therapeutic serum levels.

IV Administration:
Each dose of Coliracin can be diluted in 50 ml and administered by intravenous infusion over a 30 minutes. Patients with a totally implantable venous access device (TIVAD) in place may tolerate injection of up to 2 million units in 10 ml given over a minimum of 5 minutes.

Conversion table from CMS (colistimethate sodium) in IU (international units) to mg of CMS as well as to mg of colistin base activity (CBA):
Potency                                               ≈ mass of CMS (mg)* IU                          ≈ mg CBA
12,500                      0.4                       1
150,000                     5                         12
1,000,000                   34                        80
4,500,000                   150                       360
9,000,000                   300                       720
* Nominal potency of the drug substance = 12,500 IU/mg

Impaired Renal Function
In moderate to severe renal impairment, excretion of colistimethate sodium is delayed.
Therefore, the dose and dose interval should be adjusted in order to prevent accumulation.
The following dose adjustments are suggested:
Mild - Ccr between 20-50ml/min; BUN>60mg/100ml (>10nmol/l)
Adult dosage: 1-2 million units every 8 hours
Pediatric dosage: 12500-16000 units/kg every 8 hours
Moderate - Ccr between 10-20ml/min; BUN>100mg/100ml (>16.5nmol/l)
Adult dosage: 1 million units every 12-18 hours
Pediatric dosage: 12500 units/kg every 12-18 hours
Severe - 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.

Hepatic impairment
There are no data in patients with hepatic impairment. Caution is advised when administering colistimethate sodium in these patients.

Older people
No dose adjustments in older patients with normal renal function are considered necessary.