Colistin (Polymyxin E)

Verbatim source wording (UK SPC §4.2, SYSTEMIC TREATMENT, Adults and adolescents): 'Maintenance dose 9 million IU/day in 2-3 divided doses. In patients who are critically ill, a loading dose of 9 MIU should be administered. The most appropriate time interval to the first maintenance dose has not been established. Modelling suggests that loading and maintenance doses of up to 12 MIU may be required in patients with good renal function in some cases. Clinical experience with such doses is however extremely limited, and safety has not been established. The loading dose applies to patients with normal and impaired renal functions including those on renal replacement therapy.' NO maxDose FIELD IS DELIBERATELY POPULATED, for two reasons. First, the SPC states NO intravenous ceiling: the 12 million IU figure above is explicitly modelling with 'extremely limited' clinical experience and unestablished safety, and §4.4 adds that 'there are limited safety data for the use of high doses (> 6MIU/day)' — so it must not be recorded as a recommended maximum. Second, the only numeric ceilings in this SPC belong to the NEBULISED route (6 million IU/day in patients 2 years and over; 2 million IU/day under 2 years), and those figures are LOWER than the intravenous 9 million IU/day maintenance dose — recording either as this page's maxDose would create a false cap below the page's own intravenous dose. Both nebulised ceilings are stated inside the dose text and the paediatric notes instead. VERBATIM (§4.2, AEROSOL INHALATION, Recommended dose range): 'Adults, adolescents and children >= 2 years 1-2 MIU two to three times per day (max 6 MIU/day). Children < 2 years 0.5-1 MIU twice daily (max 2 MIU/ day).' Elderly, nebulised: 'Dose adjustment is not considered necessary.' Elderly, systemic: 'No dose adjustments in older patients with normal renal function are considered necessary.' CONVERSION TABLE (§4.2, values 'nominal and approximate only'; nominal potency 12,500 IU/mg): 1,000,000 IU is approximately 34 mg of colistimethate sodium and approximately 80 mg of colistin base activity; 4,500,000 IU is approximately 150 mg CMS and 360 mg CBA; 9,000,000 IU is approximately 300 mg CMS and 720 mg CBA. INTRATHECAL AND INTRAVENTRICULAR ROUTES (recorded for completeness, NOT this page's declared routes): 'Based on limited data, the following dose is recommended in adults: Intraventricular route 125,000 IU/day. Intrathecally administered doses should not exceed those recommended for intraventricular use. No specific dosing recommendation can be made in children for intrathecal and intraventricular routes of administration.' PREPARATION: colistimethate sodium hydrolyses to active colistin in aqueous solution; where multiple vials must be combined, reconstitution 'must be performed using strict aseptic technique'; the nebuliser solution is for single use and any remainder must be discarded. EVIDENCE CAVEAT (§4.2): 'The following dose recommendations are made based on limited population-pharmacokinetic data in critically ill patients.' §4.4 was truncated at the source-fetch limit and §4.5 (interactions) was not retrieved, so the interaction picture is incomplete.

INTRAVENOUS, verbatim (UK SPC §4.2, Paediatric population): 'The data supporting the dose regimen in paediatric patients are very limited. Renal maturity should be taken into consideration when selecting the dose. The dose should be based on lean body weight. Children <= 40kg 75,000-150,000 IU/kg/day divided into 3 doses. For children with a body weight above 40 kg, use of the dosing recommendation for adults should be considered. The use of doses >150,000 IU/kg/day has been reported in children with cystic fibrosis. There are no data regarding the use or magnitude of a loading dose in critically ill children. No dose recommendations have been established in children with impaired renal function.' ⚠️ THE 75,000 TO 150,000 IU/kg FIGURE IS A DAILY TOTAL, NOT A PER-DOSE FIGURE — it is divided into 3 doses. That is why the unit is recorded as IU/kg/day. dosePerKg IS DELIBERATELY NULL: the label gives a RANGE, not a single number, and no single value may be picked to drive a weight calculator; the dose must also be based on LEAN body weight, which a plain weight calculator does not represent. NEBULISED, verbatim: 'Adults, adolescents and children >= 2 years 1-2 MIU two to three times per day (max 6 MIU/day). Children < 2 years 0.5-1 MIU twice daily (max 2 MIU/ day)' — these are fixed doses, not weight-based. concentration IS DELIBERATELY NULL: the product is a powder reconstituted to the volume required for the chosen route (3 ml of 0.9% sodium chloride for nebulisation), not a liquid of fixed strength. §4.4: 'Caution is advised when administering colistimethate sodium to infants < 1 year of age as renal function is not fully matu[re]' (truncated at the fetch limit). Verify any under-18 use against a children's formulary and specialist microbiology or infectious-diseases advice.