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Dronabinol response

Synonyms
Marinol response; Syndros response

Summary

Dronabinol is the main psychoactive component in marijuana. Dronabinol is used in the treatment of chemotherapy-induced nausea and vomiting (CINV) among individuals who have not responded to conventional antiemetic therapy, and to treat anorexia associated with weight loss in individuals with acquired immunodeficiency syndrome (AIDS). Dronabinol is primarily metabolized by CYP2C9, which is responsible for the formation of the major active metabolite (11-hydroxy-delta-9-THC). Individuals who lack CYP2C9 activity (“CYP2C9 poor metabolizers”) have an increased exposure to dronabinol and an increased risk of side effects. Adverse events associated with dronabinol therapy include sedation, physical weakness, facial flushing, and palpitations.nThe FDA-approved drug label for dronabinol recommends monitoring for the increased adverse reactions that could potentially occur in individuals who are known to have genetic variants associated with diminished CYP2C9 function. The label states that published data indicates these individuals may have a 2- to 3-fold higher exposure to dronabinol. [from Medical Genetics Summaries]

Available tests

2 tests are in the database for this condition.

Clinical tests (2 available)

Molecular Genetics Tests

Genes See tests for all associated and related genes

  • Also known as: CPC9, CYP2C, CYP2C10, CYPIIC9, P450-2C9, P450IIC9, CYP2C9
    Summary: cytochrome P450 family 2 subfamily C member 9

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.

2020 Statement from the US Food and Drug Administration (FDA)

Dronabinol is primarily metabolized by CYP2C9 and CYP3A4 enzymes based on published in vitro studies. Inhibitors of these enzymes may increase, while inducers may decrease, the systemic exposure of dronabinol and/or its active metabolite resulting in an increase in dronabinol-related adverse reactions or loss of efficacy of dronabinol capsules.

Monitor for potentially increased dronabinol-related adverse reactions when dronabinol capsules is coadministered with inhibitors of CYP2C9 (e.g., amiodarone, fluconazole) and inhibitors of CYP3A4 enzymes (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, grapefruit juice).

[…]

Published data suggest that systemic clearance of dronabinol may be reduced and concentrations may be increased in the presence of CYP2C9 genetic polymorphism. Monitoring for potentially increased adverse reactions is recommended in patients known to carry genetic variants associated with diminished CYP2C9 function.

[…]

Published data indicate a potentially 2-to 3-fold higher dronabinol exposure in individuals carrying genetic variants associated with diminished CYP2C9 function.

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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Clinical resources

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