Is there a risk of triggering a malignant hyperthermic reaction with methylphenidate (Ritalin)?/nTh

Fråga: Is there a risk of triggering a malignant hyperthermic reaction with methylphenidate (Ritalin)? The question concerns a child born in 2003 with malignant hyperthermia (MH). Her mother also has MH.

Sammanfattning: The use of methylphenidate to children younger than 6 years of age is not approved in Sweden.

Also, a risk of triggering a malignant hyperthermic reaction cannot be excluded. Therefore using methylphenidate is not recommended in this case.

Svar: Ritalin has only been approved for children of at least 6 years of age in Sweden, because the safety and the effect are regarded as not established in younger children (1).

Drug-induced hyperthermia may result after intake of a number of drugs, including monoamine oxidase inhibitors, tricyclic antidepressants, MDMA (Ecstacy) and amphetamine. The genetic disease MH affects individuals typically after exposure to inhaled anesthetics or succinylcholine. A rapid increase in intracellular calcium increases muscle metabolism and rigidity, with rhabdomyolysis and acidosis (2).

This pharmacogenetic disorder of skeletal muscle may rarely be triggered also by vigorous exercise, heat, neuroleptic drugs or infections (3). If not treated with the muscle relaxant dantrolene sodium, the condition is often fatal. MH is a rare autosomal dominant trait, affecting between 1:3000 and 1:8500 individuals. Due to increased knowledge, the mortality has dropped from 80 % thirty years ago to less than 5 %. Malignant hyperthermic reactions are more common in young people and children under 15 years of age comprise 52.1 % of the reactions (4).

Searching Pubmed using the terms methylphenidate AND malignant hyperthermia and methylphenidate AND hyperthermia, one relevant publication was found concerning methylphenidate toxicity in patients. Hyperthermia is one of the symptoms reported in overdoses of methylphenidate (5). A search for amphetamines AND malignant hyperthermia revealed only animal and in vitro studies of MDMA and serotonin agonists as possible triggers of malignant hyperthermia.

There are four cases of fever related to the methylphenidate treatment in the Swedish adverse drug reaction register, out of a total of 119 reports. In three of the four cases, the doses were in the normal range. The reports are brief, but one concerned a patient who developed a temporary fever twice after taking the drug. Two of them also developed muscle rigidity shortly after taking the drug (6). The manufacturer of Ritalin has no records of malignant hyperthermic adverse events in patients with MH (7).