Methylene blue intravenous for adults (methylthioninium chloride)

Who can administer

Doctor only administration

Important information

• The National Poisons Information Centre (NPIC) must be contacted before using this drug
• Drug interaction potential including fatalities (see below)
• Unlicensed preparation
• Flush line before and after with Glucose 5%
• This monograph only refers to the INTRAVENOUS use of this product. For other uses (demarcation of surgical tissues and operative specimens, and as a seal test for urinary and colorectal sutures)- see manufacturers information - attached document ^{(ref 1)}

The MHRA have issued the following advice on the use of methylthioninium chloride ^{(ref 2)}

• Methylthioninium chloride by the intravenous route is approved only for drug-induced methaemoglobinaemia at a dose of 1 to 2mg/kg for adult patients
• Off-label use of methylthioninium (including use in parathyroid localisation or its use at doses exceeding the licensed dose) should be carefully evaluated in view of the potential for CNS toxicity
• Intravenous methylthioninium chloride should be avoided in patients who have been treated recently with serotonergic antidepressants, including SSRIs, SNRIs, MAOIss, clomipramine, and venlafaxine (fatalities reported)
• If use of intravenous methylthioninium chloride cannot be avoided, the lowest possible dose should be used and the patient observed closely for CNS effects for up to four hours after administration
• If features of CNS toxicity develop after use of methylthioninium, the patient should be monitored closely and given supportive care

Available preparations

Proveblue Methylthioninium chloride (methylene blue) injection 5mg per mL

Available as 10mg in 2mL and 50mg in 10mL ampoules (50mg in 10mL usually in stock)

Reconstitution

Already in solution

Draw up using a 5 micron filter needle

Infusion fluids

Glucose 5% ONLY

Methods of intravenous administration

Slow intravenous injection

• Dilute in 50 to 100mL Glucose 5%
• Administer very slowly over 5 minutes to prevent high local concentrations of the compound from producing additional methaemoglobin
• Ideally use a central line (due to extreme pH) ^{(ref 4)}

Dose in adults

Methaemoglobinaemia ^{(ref 3)}

• NPIC advice essential
• Initially, give 1 to 2mg/kg
• Seek advice from NPIC regarding repeat doses (which are normally given after 30 to 60 minutes)
• Dosing can be complicated and total doses in excess of 4mg/kg should not be given without prior discussion with the NPIC

Other indications

• See MHRA guidance above
• Doses are not given here as a result of the above MHRA guidance. However, should it be required for other indications, information is available via http://www.medicinescomplete.com/

Renal impairment

• Should be used with caution in patients with moderate to severe renal disease since there is limited data available and it is predominantly renally eliminated. Lower doses (less than 1mg/kg) may be needed

Monitoring

• May cause nausea, chest and abdominal pain, dizziness, headache, sweating, confusion, hypertension
• Monitor for serotonin syndrome if administered to patients who are on serotonergic drugs
• Methaemoglobin concentration should be measured every 60 minutes after therapy to assess effectiveness, or sooner if cyanosis recurs
• Note that methaemoglobinaemia may recur and further treatment may be required

Storage

• Store below 25⁰C
• Do not freeze or refrigerate

References

Proveblue SPC 02/2020

1. Product information Blue Marker Aquettant (attached document for use as a dye)

2: MHRA guidance April 1st 2009

3: Toxbase printed 29th September 2021

4: Injectable medicines guide- downloaded from Medusa 29th September 2021

Therapeutic classification

Antidotes and chelators