Methylthioninium chloride Proveblue 5 mg/ml solution forinjection

USED FOR

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.

You must not be given Methylthioninium chloride Proveblue:

• if you are allergic (hypersensitive) to methylthioninium chloride or other thiazine dyes
• if your body does not produce enough of the enzyme G6PD (glucose-6-phosphate dehydrogenase)
• if your body does not produce enough of the enzyme NADPH (nicotinamide adenine dinucleotide phosphate) reductase
• if your blood disorder has been caused by sodium nitrite
• if your blood disorder has been caused by chlorate poisoning.

Special care must be taken with Methylthioninium chloride Proveblue:

• if you have moderate or severe renal disease; lower doses (< 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 (see section 3 of this package leaflet)
• 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 (see section 3)
• if you suffer from hyperglycaemia or diabete mellitus, 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 discoloration is expected and will disappear after the treatment has ended

Monitoring tests

You will undergo monitoring tests during and after treatment with Methylthioninium chloride Proveblue.

If any of the above applies to you, please consult your doctor.

Children
Special care must be taken with Methylthioninium chloride Proveblue:

• in newborns and infants 3 months old or younger, lower doses are recommended (see section 3 of this package leaflet).

Taking other medicines
Please tell your doctor, pharmacist or nurse if you are taking or have recently taken any other medicine, including medicines obtained without a prescription.

You should not be given Methylthioninium chloride Proveblue at the same time you are taking certain medicines to treat depression or anxiety which affect a brain chemical called serotonin. Such medicines include Selective serotonin reuptake inhibitors SSRIs such as citalopram, escitalopram, flouextine, fluvoxamine, paroxetine, setraline and zimelidine bupropion buspirone clomipramine mirtazapine venlafaxine.

However, if the intravenous use of Methylthioninium chloride Proveblue cannot be avoided, you should be administered the lowest possible dose and observed closely for up to 4 hours after administration.

If you have any doubts about whether this medicine should be given to you, consult your doctor.

Pregnancy and breast-feeding

Ask your doctor for advice before you are given this medicine.

The use of Methylthioninium chloride Proveblue during pregnancy is not recommended unless it is clearly necessary, for example in a life-threatening situation.

Due to a lack of available data on whether methylthioninium chloride passes into human breast milk, breast-feeding should be discontinued for up to 6 days after treatment with this medicine.

Driving and using machines

Do not drive or use any tools or machines as methylthioninium chloride has moderate influence on the ability to drive and use machines.

Your doctor will inject this medicine into a vein (intravenously) slowly over a period of 5 minutes.

Adults, children above 3 months and the elderly

The usual dose is 1 to 2 mg per kilogram of your body weight, i.e. 0.2 to 0.4 ml per kilogram given over a period of 5 minutes. A second dose may be given after one hour if required.

The maximum recommended cumulative dose for the course of treatment is 7 mg/kg. If your blood disorder has been caused by aniline or dapsone, total cumulative dose should not exceed 4 mg/kg (see section 2).

Usually, treatment should not exceed one day.

Infants 3 months old or younger

The recommended dose is 0.3 to 0.5 mg/kg body weight, i.e. 0.06 to 0.1 ml/kg, over a period of 5 minutes.
A repeat dose (0.3 to 0.5 mg/kg body weight, i.e. 0.06-0.1 ml/kg) may be given after one hour in case of persistence or recurrence of symptoms. Usually, treatment should not exceed one day.

This medicine may be diluted in 50 ml glucose 50 mg/ml (5%) solution for injection to avoid local pain, in particular in children.

If you are given more Methylthioninium chloride Proveblue than you should As this medicine will be given to you whilst you are in hospital, it is unlikely that you will be given too much or too little, however, tell your doctor if you notice one of the following adverse reactions:

• feeling sick,
• stomach pain,
• chest pain,
• dizziness,
• headache,
• sweating,
• confusion,
• an increase in methaemoglobin (an abnormal form of haemoglobin in the blood),
• high blood pressure,
• shortness of breath,
• abnormally fast beating of the heart,
• tremor,
• skin discolouration. Your skin may turn blue
• reduction in red blood cells which may turn your skin pale and make you breathless and weak,
• jaundice (yellowing of the skin and eyes), this has only been reported in infants.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Like all medicines, Methylthioninium chloride Proveblue can cause side effects, although not everybody gets them.

These effects are the same in adults and children except jaundice which has only been reported in infants.

The frequencies of these side effects are not known (cannot be estimated from the available data):

high or low blood pressure irregular heartbeart, including an abnormally slow or fast beating of the heart severe allergic reactions so called anaphylactic reaction which may cause your throat or face to swell, difficulty breathing or a severe rash an increase in methaemoglobin an abnormal form of haemoglobin in the blood blue or green urine discoloured stools. They may appear green or blue skin discolouration. Your skin may turn blue feeling and being sick stomach pain chest pain headache dizziness confusion anxiety shaking sweating shortness of breath decreased haemoglobin protein in red blood cells that carry oxygen in the blood levels may be reported during blood tests reduction in red blood cells which may turn your skin pale and make you breathless and weak local tissue damage at the injection site jaundice yellowing of the skin and eyes this has only been reported in infants problems with speech agitation lack of oxygen hives fever rapid breathing dilated pupils

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

You should not be given this medicine after the expiry date which is printed on the carton, the blister and the ampoule labels after EXP. The expiry date refers to the last day of that month. The doctor or nurse will check that the expiry date on the label has not been passed before administering the injection to you.

Do not refrigerate or freeze. Keep the ampoule in the original package in order to protect from light.

The medicine must be used immediately after opening or dilution.

Do not use Methylthioninium chloride Proveblue if the solution is discoloured, cloudy, turbid, or a precipitate or particles are present. The solution is normally a clear dark blue liquid.

Any unused product or waste material should be disposed of in accordance with local requirements.

What Methylthioninium chloride Proveblue contains

• The active substance is methylthioninium chloride. Each ml of solution contains 5 mg methylthioninium chloride. Each 10 ml ampoule contains 50 mg methylthioninium chloride.
• The other ingredient is water for injections.

What Methylthioninium chloride Proveblue looks like and contents of the pack Methylthioninium chloride Proveblueis a clear dark blue solution for injection (injection) and is supplied in clear glass ampoules.
Each box contains a tray with 5 ampoules of 10 ml in blister pack.

Marketing Authorisation Holder

Provepharm SAS
Hotel Technologique, Technopôle de Château-Gombert
45 rue Frédéric Joliot Curie
13013 Marseille
France

Manufacturer

Pierrel S.p.A.
s.s. Appia 7 bis, 46/48
81043 Capua
Italy

This leaflet was last approved in

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The following information is intended for medical or healthcare professionals only:

Preparation for intravenous administration

Use immediately on opening. Inject very slowly over a period of 5 minutes.

Methylthioninium chloride 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 paediatric population. Methylthioninium chloride Proveblue must not be diluted with sodium chloride (NaCl) solution for injection because it has been demonstrated that chloride reduces the solubility of methylthioninium chloride.

Additional information on how Methylthioninium chloride Proveblue can be given is provided in section 3 of the Package Leaflet.

Any unused product or waste material should be disposed of in accordance with local requirements.