Methylthioninium chloride (methylene blue)

SPC §4.2 (Methylthioninium chloride Proveblue 5 mg/ml solution for injection) — for administration by a healthcare professional. 'Too limited data are available to support a continuous infusion dose recommendation.' Elderly: no dose adjustment is necessary. Hepatic impairment: safety and efficacy not yet established, no data available. Preparation: Proveblue is hypotonic and may be diluted in 50 ml glucose 50 mg/ml (5%) solution for injection to avoid local pain, in particular in the paediatric population — if diluted in glucose, use with caution in patients with hyperglycaemia or diabetes mellitus. §4.4: must be injected very slowly over 5 minutes to prevent high local concentrations producing additional methaemoglobin; imparts a blue-green colour to urine and faeces and a blue colour to skin which may hinder a diagnosis of cyanosis; ECG and blood pressure should be monitored during and after treatment as hypotension and cardiac arrhythmia are potential adverse reactions; check oxygen saturation by co-oximetry where available as pulse oximetry may give a false estimate during administration; failure to respond suggests cytochrome b5 reductase deficiency, G6PD deficiency or sulfhaemoglobinaemia and alternative treatment options should be considered.

TWO AGE BANDS — dosePerKg left null because the SPC gives ranges, not a single figure. Infants above 3 months, children and adolescents: 'Same posology as for adults' — 1 to 2 mg/kg body weight (0.2-0.4 ml/kg of the 5 mg/ml solution) over 5 minutes, repeatable once at one hour. Infants 3 months old or younger and newborn infants: 'The recommended dose is 0.3-0.5 mg/kg body weight, i.e. 0.06 to 0.1 ml/kg body weight, given over a period of 5 minutes'; a repeat dose of 0.3-0.5 mg/kg (0.06-0.1 ml/kg) may be given one hour after the first dose in cases of persistent or recurrent symptoms or if methaemoglobin levels remain significantly higher than the normal clinical range. §4.4 states extreme caution should be exercised when administering to newborns and infants below the age of 3 months (the reason given was truncated at the source-fetch limit). §4.2 also states methylthioninium chloride should be used with caution in infants 3 months old or younger and newborn infants with moderate to severe renal impairment (eGFR 15-59 ml/min/1.73 m2) since no data are available and it is predominantly renally eliminated — lower maximum cumulative doses (<0.5 mg/kg body weight) may be considered. Dilution in 50 ml glucose 5% is suggested to avoid local pain, in particular in the paediatric population. Verify against a children's formulary before prescribing.