Pristiq Drug Interactions

Central Nervous System (CNS)-Active Agents: The risk of using PRISTIQ in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised when PRISTIQ is taken in combination with other CNS-active drugs [see Co-administration of Drugs Containing Venlafaxine and/or Desvenlafaxine under Precautions].
Monoamine Oxidase Inhibitors (MAOI): [see Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders under Dosage & Administration, Monoamine Oxidase Inhibitors under Contraindications, and Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions under Precautions].
Serotonergic Drugs: [see Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders under Dosage & Administration, Monoamine Oxidase Inhibitors under Contraindications, and Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions under Precautions].
Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin): Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. These studies have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are co-administered with warfarin. Patients receiving warfarin therapy should be carefully monitored when PRISTIQ is initiated or discontinued.
Ethanol: A clinical study has shown that desvenlafaxine does not increase the impairment of mental and motor skills caused by ethanol. However, as with all CNS-active drugs, patients should be advised to avoid alcohol consumption while taking PRISTIQ.
Potential for Other Drugs to Affect Desvenlafaxine: Inhibitors of CYP3A4 (ketoconazole): CYP3A4 is minimally involved in desvenlafaxine elimination. In a clinical trial, ketoconazole (200 mg BID) increased the area under the concentration vs. time curve (AUC) of PRISTIQ (400 mg single dose) by about 43%, a weak interaction, and C_max by about 8%. Concomitant use of PRISTIQ with potent inhibitors of CYP3A4 may result in higher exposure to PRISTIQ.
Inhibitors of other CYP enzymes: Based on in vitro data, drugs that inhibit CYP isozymes 1A1, 1A2, 2A6, 2D6, 2C8, 2C9, 2C19, and 2E1 are not expected to have significant impact on the pharmacokinetic profile of PRISTIQ.
Potential for Desvenlafaxine to Affect Other Drugs: Drugs metabolized by CYP2D6 (desipramine): In vitro studies showed minimal inhibitory effect of desvenlafaxine on CYP2D6.
Clinical trials have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at the dose of 100 mg daily. When desvenlafaxine succinate was administered at a dose of 100 mg daily in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the C_max and AUC of desipramine increased approximately 25% and 17%, respectively. When 400 mg (8 times the recommended 50 mg dose) was administered, the C_max and AUC of desipramine increased approximately 50% and 90%, respectively. When desvenlafaxine succinate was administered at a dose of 100 mg daily in conjunction with a single 60 mg dose of codeine, a CYP2D6 substrate metabolized to morphine, the AUC of codeine was unchanged, the AUC of morphine decreased approximately 8%. Concomitant use of desvenlafaxine with a drug metabolized by CYP2D6 may result in increased concentrations of that drug and decreased concentrations of its CYP2D6 metabolites.
Drugs metabolized by CYP3A4 (midazolam): In vitro, desvenlafaxine does not inhibit or induce the CYP3A4 isozymes.
In a clinical trial, PRISTIQ 400 mg daily (8 times the recommended 50 mg dose) was co-administered with a single 4 mg dose of midazolam (a CYP3A4 substrate). The AUC and C_max of midazolam decreased by approximately 31% and 16%, respectively. In a second study, PRISTIQ 50 mg daily was co-administered with a single 4 mg dose of midazolam. The AUC and C_max of midazolam decreased by approximately 29% and 14%, respectively. Concomitant use of PRISTIQ with a drug metabolized by CYP3A4 may result in lower exposure to that drug.
Drugs metabolized by a combination of both CYP2D6 and CYP3A4 (tamoxifen and aripiprazole): Clinical studies have shown that desvenlafaxine (100 mg daily) does not have a clinically relevant effect on drugs metabolized by a combination of both CYP2D6 and CYP3A4 enzymes.
A single 40 mg dose of tamoxifen, which is metabolized to active metabolites 4-hydroxy-tamoxifen and endoxifen primarily by CYP2D6 with minor contributions to metabolism by CYP3A4, was administered in conjunction with desvenlafaxine succinate (100 mg daily). The AUC increased by 3% with concomitant administration of desvenlafaxine succinate. The AUC of 4-hydroxy-tamoxifen increased by 9%. Endoxifen AUC was decreased by 12%.
Desvenlafaxine succinate was administered at a dose of 100 mg daily in conjunction with a single 5 mg dose of aripiprazole, a CYP2D6 and CYP3A4 substrate metabolized to the active metabolite dehydro-aripiprazole. The AUC of aripiprazole increased by 6%, with concomitant administration of desvenlafaxine succinate. The AUC of dehydro-aripiprazole increased by 3%, with concomitant administration.
Drugs metabolized by CYP1A2, 2A6, 2C8, 2C9 and 2C19: In vitro, desvenlafaxine does not inhibit CYP1A2, 2A6, 2C8, 2C9, and 2C19 isozymes and would not be expected to affect the pharmacokinetics of drugs that are metabolized by these CYP isozymes.
P-glycoprotein Transporter: In vitro, desvenlafaxine is not a substrate or an inhibitor for the P-glycoprotein transporter.
The pharmacokinetics of PRISTIQ are unlikely to be affected by drugs that inhibit the P-glycoprotein transporter, and desvenlafaxine is not likely to affect the pharmacokinetics of drugs that are substrates of the P-glycoprotein transporter.
Electroconvulsive Therapy: There are no clinical data establishing the risks and/or benefits of electroconvulsive therapy combined with PRISTIQ treatment for MDD.
Drug-Laboratory Test Interactions: False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking desvenlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of desvenlafaxine therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish desvenlafaxine from PCP and amphetamine.