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Pristiq (Desvenlafaxine Succinate) - Drug Interactions, Contraindications, Overdosage, etc



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 Warnings and Precautions ( 5.13 )].

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 PRISTIQ (SNRIs or SSRIs), or who have recently had SNRI or SSRI therapy discontinued prior to initiation of an MAOI [see Contraindications ( 4.2 )].

Serotonergic Drugs

Based on the mechanism of action of PRISTIQ and the potential for serotonin syndrome, caution is advised when PRISTIQ is co-administered with other drugs that may affect the serotonergic neurotransmitter systems [see Warnings and Precautions ( 5.2 )].

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 coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when PRISTIQ is initiated or discontinued.


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


Human Experience with Overdosage

There is limited clinical experience with desvenlafaxine succinate overdosage in humans. In pre-marketing clinical studies, no cases of fatal acute overdose of desvenlafaxine were reported.

Among the patients included in the MDD pre-marketing studies of PRISTIQ, there were four adults who ingested desvenlafaxine succinate (4000 mg [desvenlafaxine alone], 900, 1800 and 5200 mg [in combination with other drugs]); all patients recovered. In addition, one patient's 11-month-old child accidentally ingested 600 mg of desvenlafaxine succinate, was treated, and recovered. The adverse reactions reported within 5 days of an overdose > 600 mg that were possibly related to PRISTIQ included: headache, vomiting, agitation, dizziness, nausea, constipation, diarrhea, dry mouth, paresthesia, and tachycardia.

Desvenlafaxine (PRISTIQ) is the major active metabolite of venlafaxine. Overdose experience reported with venlafaxine (the parent drug of PRISTIQ) is presented below; the identical information can be found in the Overdosage section of the venlafaxine package insert.

In postmarketing experience, overdose with venlafaxine (the parent drug of PRISTIQ) has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), sinus and ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported.

Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher pre-existing burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage, as opposed to some characteristic(s) of venlafaxine-treated patients, is not clear.

Prescriptions for PRISTIQ should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Management of Overdosage

Treatment should consist of those general measures employed in the management of overdosage with any SSRI/SNRI.

Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal should be administered.

Induction of emesis is not recommended. Because of the moderate volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for desvenlafaxine are known.

In managing an overdose, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians Desk Reference® (PDR).



Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the PRISTIQ formulation.

Monoamine Oxidase Inhibitors

PRISTIQ must not be used concomitantly in patients taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days due to the risk of serious, sometimes fatal, drug interactions with SNRI or SSRI treatment or with other serotonergic drugs. These interactions have been associated with symptoms that include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. Based on the half-life of desvenlafaxine, at least 7 days should be allowed after stopping PRISTIQ before starting an MAOI [see Dosage and Administration ( 2.6)].


Controlled Substance

Desvenlafaxine is not a controlled substance.

Abuse and Dependence

Although PRISTIQ has not been systematically studied in preclinical or clinical studies for its potential for abuse, no indication of drug-seeking behavior was seen in the clinical studies. However, it is not possible to predict on the basis of pre-marketing experience, the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of PRISTIQ (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

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