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Central Nervous System (CNS)-Active Agents

The risk of using Pristiq (Desvenlafaxine) in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised when this medicine is taken in combination with other CNS-active drugs.

Monoamine Oxidase Inhibitors (MAOI)

Adverse reactions, some of which were serious, have been reported in patients who have recently been discontinued from a monoamine oxidase inhibitor (MAOI) and started on antidepressants with pharmacological properties similar to Desvenlafaxine (SNRIs or SSRIs), or who have recently had SNRI or SSRI therapy discontinued prior to initiation of an MAOI.

Serotonergic Drugs

Based on the mechanism of action of Pristiq (Desvenlafaxine) and the potential for serotonin syndrome, caution is advised when this drug is co-administered with other drugs that may affect the serotonergic neurotransmitter systems.

Drugs that Interfere with Hemostasis (e.g., NSAIDs, Warfarin, and Aspirin)

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 coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when Pristiq (Desvenlafaxine Succinate) is initiated or discontinued.

Ethanol (Alcohol)

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 Desvenlafaxine (Pristiq).

Potential for other Drugs to Affect Desvenlafaxine

Inhibitors of CYP3A4 (ketoconazole)

CYP3A4 is a minor pathway for the metabolism of Pristiq (Desvenlafaxine). In a clinical study, ketoconazole (200 mg BID) increased the area under the concentration vs. time curve (AUC) of this medicine (400 mg single dose) by about 43% and Cmax by about 8%. Concomitant use of Pristiq (Desvenlafaxine) with potent inhibitors of CYP3A4 may result in higher concentrations of this drug.

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 (Desvenlafaxine Succinate).

Potential for Desvenlafaxine to Affect other Drugs

Drugs metabolized by CYP2D6 (desipramine)

In vitro studies showed minimal inhibitory effect of desvenlafaxine on CYP2D6.

Clinical studies 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 Cmax and AUC of desipramine increased approximately 25% and 17%, respectively. When 400 mg (8 times the recommended 50 mg dose) was administered, the Cmax and AUC of desipramine increased approximately 50% and 90%, respectively. Concomitant use of desvenlafaxine with a drug metabolized by CYP2D6 can result in higher concentrations of that drug.

Drugs metabolized by CYP3A4 (midazolam)

In vitro, desvenlafaxine does not inhibit or induce the CYP3A4 isozyme.

In a clinical study, Pristiq (Desvenlafaxine) 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 Cmax of midazolam decreased by approximately 31% and 16%, respectively. Concomitant use of this medicine with a drug metabolized by CYP3A4 can result in lower exposures to that drug.

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 Desvenlafaxine (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 (Desvenlafaxine) treatment.

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