Valbenazine (Ingrezza), deutetrabenazine (Austedo) and tetrabenazine

They are medicines for movements a person cannot control: tardive dyskinesia, which can follow years of some psychiatric medicines, and the jerky movements of Huntington's disease, called chorea. Valbenazine is sold as Ingrezza, deutetrabenazine as Austedo, and tetrabenazine as Xenazine. All three lower dopamine signalling in the part of the brain that drives these movements.

CYP2D6 is a liver enzyme that breaks these medicines down. Some people are born with two copies of CYP2D6 that barely work, called poor metabolisers. In them the medicine builds up: on valbenazine, the active part reaches about 2 times the usual level. The Ingrezza label puts poor metabolisers at about 7% of White people and about 2% of Asian and African American people.

Ingrezza: 40 mg once a day, where the usual target is 80 mg. Austedo and Austedo XR: no more than 36 mg a day in total. Tetrabenazine: no more than 50 mg a day, and no more than 25 mg at one time; people who clear it normally can go up to 100 mg a day, 37.5 mg at a time.

For tetrabenazine, the label says anyone who needs more than 50 mg a day should be genotyped for CYP2D6 first, and the dose then set by the result. The Ingrezza and Austedo labels give the lower dose for people known to be poor metabolisers but do not ask for a test. Many people learn their CYP2D6 type from an earlier pharmacogenomic test; if you have one, show it to the prescriber.

Too much of these medicines can cause sleepiness, restlessness and, with valbenazine, a change in heart rhythm on the ECG called QT prolongation. The Ingrezza label says this is more likely in poor metabolisers, which is why their dose is lower. All three labels also carry a warning about depression and suicidal thoughts in people with Huntington's disease.