Proveblue Special Precautions

General: Long term administration of methylene blue may result in marked anaemia due to accelerated destruction of erythrocytes; haemoglobin concentrations should be checked frequently.
Methaemoglobin levels should be monitored throughout therapy.
If methylene blue is injected subcutaneously or if extravasation occurs, necrotic abscesses may occur (see Contraindications). Slow injection rates are recommended to prevent high local concentration of the compound.
Proveblue must be injected very slowly over a period of 5 minutes to prevent high local concentrations of the compound from producing additional methaemoglobin.
It imparts a blue-green colour to urine, faeces and a blue colour to skin which may hinder a diagnosis of cyanosis.
In patients with aniline-induced methaemoglobinaemia, repeated doses of methylthioninium chloride may be required. Caution should be exercised in the course of treatment with methylthioninium chloride as this may exacerbate Heinz body formation and haemolytic anaemia. Lower doses should therefore be considered and total cumulative dose should not exceed 4 mg/kg.
Proveblue can exacerbate dapsone-induced haemolytic anemia because of the formation of the dapsone reactive metabolite hydroxylamine which oxidises haemoglobin. It is recommended not to exceed a cumulative dose for the course of treatment of 4 mg/kg in patients with dapsone-induced methaemoglobinaemia.
In cases of suspected methaemoglobinaemia, it is advisable to check the oxygen saturation by cooximetry when available since pulse oximetry may provide a false estimation of oxygen saturation during administration of methylthioninium chloride.
Anaesthesiologists should be vigilant for methaemoglobinaemia in patients receiving dapsone therapy and for BIS (Bispectral Index) interference with Proveblue administration.
Electrocardiogram (ECG) and blood pressure should be monitored during and after treatment with Proveblue as hypotension and cardiac arrhythmia are potential adverse reactions (see Adverse Reactions).
Failure to respond to methylthioninium chloride suggests cytochrome b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency or sulfhaemoglobinemia. Alternative treatment options should be considered.
Methylthioninium chloride may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Avoid concomitant use of methylthioninium chloride with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (see Interactions).
Patients treated with methylthioninium chloride in combination with serotonergic drugs should be monitored for the emergence of serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use of methylthioninium chloride, and initiate supportive treatment.
Patients with hyperglycaemia or diabetes mellitus: If diluted in glucose 50 mg/ml (5%) solution for injection, methylthioninium chloride must be used with caution in patients with hyperglycaemia or diabetes mellitus, as these conditions may be exacerbated by the glucose solution.
Photosensitivity: Methylthioninium chloride may cause a cutaneous photosensitivity reaction when exposed to strong light sources, such as phototherapy, those found in operating theatres or locally from illuminating devices such as pulse oximeters.
Advise patients to take protective measures against exposure to light, because photosensitivity may occur after administration of methylthioninium chloride.
Effects on Ability to Drive and Use Machines: Methylthioninium chloride has moderate influence on the ability to drive and use machines. Indeed, driving can be affected due to confusional state, dizziness and possibly eye disturbances. However, the risk is limited as the medicinal product is intended for acute administration only in emergency situations at hospital.
Use in Children: Safety and efficacy of methylthioninium chloride in infants have not been established. It has been reported that the metabolism of methylthioninium chloride to leucomethylene blue is likely to be less efficient in neonates, due to reduced efficiency of NADPH-diaphorase in this age group. The use of methylene blue in infants up to 4 months of age is not recommended.
Extreme caution should be exercised when administering to the newborns and infants below the age of 4 months due to lower concentrations of NADPH-methaemoglobin reductase necessary for reducing methaemoglobin to haemoglobin, making these infants more susceptible to methaemoglobinaemia produced by high doses of methylthioninium chloride.