SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Methylthioninium Chloride Injection USP 1% w/v

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Contains: Methylthioninium Chloride USP 1% w/v

3.    PHARMACEUTICAL FORM

Sterile Aqueous Injection

4.    CLINICAL PARTICULARS

4.1    Therapeutic Indications

Drug induced methaemoglobinaemia

4.2    Posology and Method of administration

Inject Methylthioninium Chloride very slowly over several minutes.

Route of administration: Intravenous Injection.

Adults and the elderly    Children

0.1 - 0.2ml/kg body weight.    Not recommended

4.3    Contraindications

Not to be administered by intra-spinal injection or subcutaneous injection. Glucose-6-phosphate dehydrogenase deficiency and sodium nitrite induced methaemaglobinaemia.

4.4    Special Warnings and Special Precautions for Use

Methylthioninium Chloride must be injected very slowly over a period of several minutes to prevent high local concentrations of the compound from producing additional methaemoglobin. Do not exceed the recommended dosage. Severe renal impairment and aniline-induced methaemaglobinaemia as his may precipitate Heinz body formation and haemolytic anaemia.

4.5    Interaction with other medicinal products and other forms of interaction

Adverse CNS effects including confusion, disorientation, agitation, expressive aphasia, altered muscle tone in limbs, hypoxia, ocular symptoms, and depressed level of consciousness have been reported following intravenous infusion of methylthioninium chloride for parathyroid surgery.The use of methylthioninium for localisation in parathyroid surgery falls outside the approved indications (see section 4.1). Toxicity has occurred with doses of 3 mg/kg and in one case adverse CNS effects were reported after a dose of 1.75 mg/kg in a woman weighing 115 kg. The affected patients had been treated with serotonergic drugs. Methylthioninium should preferably be avoided in patients receiving drugs that enhance serotonergic transmission including SSRIs, bupropion, buspirone, clomipramine, mirtazapine, and venlafaxine. If the intravenous use of methylthioninium cannot be avoided in patients treated with serotonergic drugs, the lowest possible dose should be chosen and the patient observed closely for CNS effects for up to 4 hours after administration.

4.6    Pregnancy and Lactation

As with all drugs during Pregnancy, care should be taken in assessing the risk to benefit ratio.

4.7 Effects on Ability to Drive and Use Machines

None known

4.8 Undesirable Effects

Large intravenous doses of Methylthioninium Chloride produce nausea, abdominal and precordial pain, dizziness, headache, profuse sweating, mental confusion and the formation of methaemoglobin, also hypertension.

4.9 Overdose

The symptoms of overdose are as above. The patient should be maintained under observation and appropriate supportive measures taken as necessary.

5.    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic Properties

In-vivo, in low concentration, Methylthioninium Chloride speeds up the conversion of methaemoglobin to haemoglobin.

5.2    Pharmacokinetic Properties

After i.v. administration Methylthioninium Chloride is rapidly taken up by the tissues. It is also well absorbed by the oral route. The majority of the dose is excreted in the urine, usually in the form of leuco Methylthioninium Chloride.

5.3    Preclinical Safety Data

There are no additional pre-clinical data of relevance to the prescriber.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Water for Injections BP to 100%

6.2    Incompatibilities

None stated

6.3    Shelf Life

Unopened ampoules: 5 years (60 Months).

6.4    Special Precautions for Storage

Store below 25 °C

6.5 Nature and Contents of Container

Clear colourless neutral glass ampoules containing 10ml of product. Packs of 10 ampoules in suitable cartons are available.

6.6 Instructions for Use/Handling

Use immediately on opening. Inject very slowly over several minutes. Administer through a sterile 0.45 micron Filter.

7. MARKETING AUTHORISATION HOLDER

Martindale Pharmaceuticals Limited.

Bampton Road Romford RM3 8UG

8.    MARKETING AUTHORISATION NUMBER(S)

Methylthioninium Chloride Injection USP 1%w/v PL 0156/0039

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/03/2009

10    DATE OF REVISION OF THE TEXT

10/03/2009