Pharmacokinetics

The metabolism of PRISTIQ is independent of the CYP2D6 pathway in the liver¹

PRISTIQ demonstrated consistent pharmacokinetics regardless of CYP2D6 metabolizer status.^1,2

Data from an open-label, 2-period, parallel-group, crossover study evaluating single doses of PRISTIQ 100 mg in healthy subjects who are extensive or poor CYP2D6 substrate metabolizers (N=14). The primary objective was to determine the difference in the pharmacokinetics of PRISTIQ when influenced by CYP2D6 polymorphism.

Effects on CYP2D6 and CYP3A4¹

• In vitro studies showed minimal inhibitory effect on CYP2D6¹
• Clinical studies have shown that PRISTIQ does not have a clinically relevant effect on levels of a CYP2D6-metabolized drug when coadministered¹
• PRISTIQ has a low potential for CYP2D6-mediated drug-drug interactions¹
  • — PRISTIQ 100 mg was associated with a 17% increase in AUC of a CYP2D6-metabolized drug when coadministered. A higher dose (400 mg, 8 times the recommended therapeutic dose) was associated with a 90% increase¹
• In vitro, PRISTIQ does not inhibit or induce the CYP3A4 isozyme¹
• In clinical studies, at a dose of 400 mg (8 times the recommended therapeutic dose)¹:
  • — Coadministration of PRISTIQ with a CYP3A4 inhibitor was associated with a 43% increase in AUC of PRISTIQ. Concomitant use of PRISTIQ with potent inhibitors of CYP3A4 may result in higher concentrations of PRISTIQ¹
  • — PRISTIQ was associated with a 31% decrease in AUC of a CYP3A4-metabolized drug when coadministered. Concomitant use of PRISTIQ with a drug metabolized by CYP3A4 can result in lower exposures to that drug¹

Clinical Pharmacology of PRISTIQ¹

Important Treatment Considerations

• PRISTIQ must not be used concomitantly with an MAOI or within 14 days of stopping an MAOI. Allow 7 days after stopping PRISTIQ before starting an MAOI.
• Development of a potentially life-threatening serotonin syndrome may occur with SNRIs and SSRIs, including PRISTIQ, particularly with concomitant use of serotonergic drugs, including triptans, and with drugs that impair the metabolism of serotonin (including MAOIs). If concomitant use is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Concomitant use of PRISTIQ with serotonin precursors is not recommended.
• SSRIs and SNRIs, including PRISTIQ, may increase the risk of bleeding events. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk.

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