Daptomycin (Burns — MRSA/VRE)

SCOPE - what is published is the SPC's complicated skin and soft-tissue infection posology, which is this burns page's primary indication (a burn wound infection is a complicated skin and soft-tissue infection). THE PAGE'S 'VRE' FRAMING IS NOT DOSED BY THE SOURCE, and the exclusion is stated at the head of the dose field rather than left in these notes. §4.4 verbatim: 'There is insufficient evidence to be able to draw any conclusions regarding the possible clinical efficacy of Cubicin against infections due to enterococci, including Enterococcus faecalis and Enterococcus faecium. In addition, dose regimens of daptomycin that might be appropriate for the treatment of enterococcal infections, with or without bacteraemia, have not been identified. Failures with daptomycin in the treatment of enterococcal infections that were mostly accompanied by bacteraemia have been reported. In some instances treatment failure has been associated with the selection of organisms with reduced susceptibility or frank resistance to daptomycin.' EDITORIAL RECOMMENDATION: retitle this page to MRSA / cSSTI only, or split the VRE indication onto its own page and withhold a dose there - a clinician arriving via the 'VRE' label and reading the cSSTI band would be under-dosing enterococcal disease. VERBATIM §4.2 ADULT POSOLOGY: '- cSSTI without concurrent SAB: Cubicin 4 mg/kg is administered once every 24 hours for 7-14 days or until the infection is resolved.' '- cSSTI with concurrent SAB: Cubicin 6 mg/kg is administered once every 24 hours.' '- Known or suspected RIE due to Staphylococcus aureus: Cubicin 6 mg/kg is administered once every 24 hours' - right-sided infective endocarditis is a different clinical setting from a burn wound infection, so it is quoted here rather than in the dose field; §4.4 adds that clinical data for it 'are limited to 19 adult patients' and that efficacy 'in patients with prosthetic valve infections or with left-sided infective endocarditis due to Staphylococcus aureus has not been demonstrated'. US label agrees: §2.2 '4 mg/kg ... once every 24 hours for 7 to 14 days' for cSSSI, §2.4 '6 mg/kg ... once every 24 hours for 2 to 6 weeks' for S. aureus bacteraemia including right-sided infective endocarditis. OTHER §4.4 STATEMENTS DIRECTLY RELEVANT TO BURNS: 'It has been demonstrated in clinical studies that Cubicin is not effective in the treatment of pneumonia. Cubicin is therefore not indicated for the treatment of pneumonia.' 'Patients with deep-seated infections should receive any required surgical interventions (e.g. debridement, removal of prosthetic devices, valve replacement surgery) without delay.' 'If a focus of infection other than cSSTI or RIE is identified after initiation of Cubicin therapy consideration should be given to instituting alternative antibacterial therapy that has been demonstrated to be efficacious in the treatment of the specific type of infection(s) present.' §4.2 also states: 'Creatine phosphokinase (CPK) levels must be measured at baseline and at regular intervals (at least weekly) during treatment.' The highest adult band anywhere in the fetched UK or US text is 6 milligrams per kilogram once every 24 hours; nothing above that appears for adults. The SPC criterion is CREATININE CLEARANCE below 30 ml/min, and the dose that is given every 48 hours differs by indication (see renalAdjustment). §4.4 also records a laboratory-interference trap: 'False prolongation of prothrombin time (PT) and elevation of international normalised ratio (INR) have been observed when certain recombinant thromboplastin reagents are utilised for the assay.' TRUNCATION CAVEAT: UK §4.4 and §4.8 and US §2.6, §5, §6, §7 and §8.1 were cut off at the fetch limit, so the warnings, adverse-reaction and interaction material below is incomplete.

dosePerKg IS DELIBERATELY null: the paediatric regimen is AGE-BANDED, not a single per-kilogram figure, so no one number is valid across the paediatric range and a weight calculator must not be fed one. VERBATIM §4.2 'Paediatric population (1 to 17 years of age)' - cSSTI WITHOUT S. aureus bacteraemia: 12 to 17 years '5 mg/kg once every 24 hours infused over 30 minutes'; 7 to 11 years '7 mg/kg once every 24 hours infused over 30 minutes'; 2 to 6 years '9 mg/kg once every 24 hours infused over 60 minutes'; 1 to under 2 years '10 mg/kg once every 24 hours infused over 60 minutes'. Duration up to 14 days. cSSTI ASSOCIATED WITH S. aureus bacteraemia: 12 to 17 years '7 mg/kg once every 24 hours infused over 30 minutes'; 7 to 11 years '9 mg/kg once every 24 hours infused over 30 minutes'; 2 to 6 years '12 mg/kg once every 24 hours infused over 60 minutes'; 1 to under 2 years '12 mg/kg once every 24 hours infused over 60 minutes'. The US label states the same figures, giving a single '1 to 6 years 12 mg/kg' band for bacteraemia and a duration of up to 42 days. AGE FLOOR, verbatim §4.2: 'Paediatric patients below the age of one year should not be given Cubicin due to the risk of potential effects on muscular, neuromuscular and/or nervous systems (either peripheral and/or central) that were observed in neonatal dogs.' RENAL: 'The dosage regimen for Cubicin in paediatric patients with renal impairment has not been established'; the US label adds 'Daptomycin is not indicated in pediatric patients with renal impairment because dosage has not been established in these patients.' §4.4: 'The safety and efficacy of Cubicin in children and adolescents aged below 18 years with right-sided infective endocarditis (RIE) due to Staphylococcus aureus have not been established.' CONCENTRATION: 50 mg per mL is the reconstituted concentration stated verbatim in the US label §2.1 - 'Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg per mL)'; the UK §6.6 reconstitution text was not fetched, so confirm against the product in use before calculating a volume. The reconstituted solution is then given in 0.9% sodium chloride. Verify all paediatric dosing against a children's formulary.