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Dronabinol response

MedGen UID:
941226
Concept ID:
CN258190
Sign or Symptom
Synonyms: Marinol response; Syndros response
Drug:
dronabinol
MedGen UID:
21110
Concept ID:
C0039663
Pharmacologic Substance
An isomer of tetrahydrocannabinol (THC) that is the main and most active isomer found in the Cannabis sativa L. plant, with potential anti-emetic, analgesic and appetite stimulating activities. Upon administration, dronabinol, also called delta-9-THC, targets and binds to cannabinoid receptors (CBRs) located in the central nervous system (CNS). Dronabinol acts directly on the appetite and vomiting control centers in the brain to stimulate appetite and prevent emesis. In addition, this agent induces analgesia. Urine levels may be used as a marker to determine the exposure to certain preparations containing parts of the cannabis plant, such as marijuana. [from NCI]
 
Gene (location): CYP2C9 (10q23.33)

Definition

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]

Professional guidelines

PubMed

Filippini G, Minozzi S, Borrelli F, Cinquini M, Dwan K
Cochrane Database Syst Rev 2022 May 5;5(5):CD013444. doi: 10.1002/14651858.CD013444.pub2. PMID: 35510826Free PMC Article
Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L
Cochrane Database Syst Rev 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2. PMID: 34532852Free PMC Article
Himmerich H, Kan C, Au K, Treasure J
Pharmacol Ther 2021 Jan;217:107667. Epub 2020 Aug 25 doi: 10.1016/j.pharmthera.2020.107667. PMID: 32858054

Curated

UK NICE Guideline NG144, Cannabis-based medicinal products, 2021

DailyMed Drug Label, DRONABINOL, 2020

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted 1 information 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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