Methylthioninium chloride is approved for the management of drug-induced methaemoglobinaemia in adults. It is also used for other purposes, but these uses are not covered by the product licence.

On the basis of 27 reports of CNS ( central nervous system ) toxicity associated with Methylthioninium, the January 2008 issue of Drug Safety Update advised how the risk could be minimised.
The Summary of Product Characteristics for Methylthioninium chloride has now been updated to mention the possibility of CNS toxicity in patients being treated with serotonergic drugs such as selective serotonin reuptake inhibitor ( SSRI ) antidepressants, Clomipramine, and Venlafaxine. Features of toxicity include confusion, disorientation, agitation, expressive aphasia, altered muscle tone in limbs, hypoxia, ocular symptoms, and depressed level of consciousness.

All cases reviewed described CNS toxicity after the use of Methylthioninium as a visualising agent in parathyroid or thyroid surgery. Since the review, further cases of CNS toxicity in association with Methylthioninium have come to light. Five of the new cases involved parathyroid surgery ( two cases reported to us on Yellow Cards and three documented in the literature ). However, a further new case of CNS toxicity involved the use of Methylthioninium for management of uncontrollable hypotension during cardiac surgery.

In all new cases, the patients were being treated with either an SSRI antidepressant or Clomipramine, and the features of toxicity were similar to those reported previously. In four cases, the reporters labelled the reaction as serotonin syndrome. These additional reports, which bring the total number of cases to 33, reinforce the possibility that CNS toxicity results from an interaction between a serotonergic drug and Methylthioninium. When reporting a suspected adverse drug reaction to us on a Yellow Card, it is helpful if you can give information on the patient’s outcome; this helps us prioritise the information. As with visualisation in surgical procedures, the management of intractable hypotension is not an approved indication for Methylthioninium chloride.

Source: MHRA, 2009

XagenaMedicine2009



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