Methylthioninium chloride (also called methylene blue) belongs to a group of medicines called antidotes. Methylthioninium chloride (Proveblue) will be given to you or your child (0-17 years old) to treat problems with your blood resulting from exposure to some medicines or chemicals that can cause a disease called methaemoglobinaemia.
In methaemoglobinaemia, your blood contains too much methaemoglobin (an abnormal form of haemoglobin that is not able to transport oxygen around your body effectively). This medicine will help your haemoglobin return to normal and restore the transport of oxygen in the blood.
Acute symptomatic treatment of medicinal and chemical products-induced methaemoglobinaemia. Methylthioninium chloride Proveblue is indicated in adults, children and adolescents (aged 0 to 17 years old)
• Hypersensitivity to the active substance, or to any other thiazine dyes
• Patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of haemolytic anaemia
• Patients with nitrite-induced methaemoglobinaemia during treatment of cyanide poisoning
• Patients with methaemoglobinaemia due to chlorate poisoning
• Deficiency in NADPH (nicotinamide adenine dinucleotide phosphate) reductase.
Warnings and precautions
• If you have moderate or severe renal disease; lower doses (less than 1 mg/kg) may be needed
• If your blood disorder has been caused by a chemical called aniline, which is contained in dyes; lower doses may be needed and total cumulative dose should not exceed 4 mg/kg
• If your blood disorder has been caused by a medicine called dapsone (used to treat leprosy and other skin conditions); lower doses may be needed and total cumulative dose should not exceed 4 mg/kg
• If you suffer from hyperglycaemia or diabetesmellitus, as these conditions may be worsened by the glucose solution used for the dilution of the medicine
• Your urine and stools may turn a blue-green colour; and skin may possibly turn a blue colour when you are treated with Methylthioninium chloride (Proveblue). This discolouration is expected and will disappear after the treatment has ended
The usual dose is 1 to 2 mg per kg body weight, i.e. 0.2-0.4 ml per kg body weight, given over a period of 5 minutes. A repeat dose (1 to 2 mg/kg body weight, i.e. 0.2-0.4 ml/kg body weight) 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. Treatment does not usually exceed one day.
The maximum recommended cumulative dose for the course of treatment is 7 mg/kg and should not be exceeded, since Methylthioninium chloride administered above the maximum dose may cause methaemoglobinaemia in susceptible patients.
In the case of aniline- or dapsone-induced methaemaglobinaemia, the maximum recommended cumulative dose for the course of treatment is 4 mg/kg
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.
Extreme caution should be exercised when administering to newborns and infants below the age of 3 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.
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.
There are no adequate data from the use of methylthioninium chloride in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Methylthioninium chloride Proveblue should not be used during pregnancy unless clearly necessary, e.g. in life-threatening methaemoglobinaemia.
It is unknown whether methylthioninium chloride is excreted in human breast milk. The excretion of methylthioninium chloride in milk has not been studied in animals. A risk to the suckling child cannot be excluded. Based on kinetic data, breast-feeding should be discontinued for up to 8 days after treatment with Methylthioninium chloride Proveblue.
In vitro, methylthioninium chloride has been shown to reduce motility of human sperm in a dose dependant manner.
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.
• Very common side effects (may affect more than 1 in 10 people)
Pain in extremity | dizziness | sweating | skin discoloration. Your skin may turn blue | blue or green urine | numbness and tingling | abnormal taste in mouth | nausea
• Common side effects (may affect up to 1 in 10 people): Stomach pain | chest pain | headache | anxiety | injection site pain | vomiting