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GTR Home > Conditions/Phenotypes > Thioridazine response

Thioridazine response

Synonyms
Mellaril response

Summary

Thioridazine is an antipsychotic used in the treatment of schizophrenia and psychosis. Its use is reserved for patients who have failed to respond to or cannot tolerate other antipsychotics. Thioridazine has been shown to prolong the QT interval (the time taken for the heart ventricles to depolarize and repolarize) in a dose related manner. Drugs with this potential have been associated with the life-threatening ventricular tachycardia, "torsades de pointes". The CYP2D6 enzyme is involved in metabolizing thioridazine. About 7% of the population has reduced enzyme activity because of variants in the CYP2D6 gene. In individuals with low CYP2D6 activity, standard doses of thioridazine may lead to higher drug levels in the plasma, and increase the risk of cardiac arrhythmias. The FDA-approved drug label for thioridazine states that thioridazine is contraindicated in individuals who are known to have reduced levels of CYP2D6 activity. The label also states it is contraindicated to coadminister thioridazine with drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine) or inhibit the metabolism of thioridazine (e.g., fluvoxamine, propranolol, and pindolol). [from Medical Genetics Summaries]

Available tests

8 tests are in the database for this condition.

Clinical tests (8 available)

Molecular Genetics Tests

Genes See tests for all associated and related genes

  • Also known as: CPD6, CYP2D, CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2, CYP2DL1, CYPIID6, P450-DB1, P450C2D, P450DB1, CYP2D6
    Summary: cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene)

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted1information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2016 Statement from the US Food and Drug Administration (FDA): Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias. Such an increased risk may result also from the additive effect of coadministering thioridazine with other agents that prolong the QTc interval. Therefore, thioridazine is contraindicated with these drugs as well as in patients, comprising about 7% of the normal population, who are known to have a genetic defect leading to reduced levels of activity of P450 2D6.

Please review the complete therapeutic recommendations that are located here: (1).

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug.

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