Medical Information
United States
 

In order to provide you with relevant and meaningful content we need to know more about you.

Please choose the category that best describes you.

This content is intended for U.S. Healthcare Professionals. Would you like to proceed?

I am a U.S. Healthcare ProfessionalYes, I am a U.S. Healthcare Professional
SelectI am a U.S. Healthcare ProfessionalYes, I am a U.S. Healthcare Professional
I am a U.S. Patient / CaregiverNo, go back to the patient portal
SelectI am a U.S. Patient / CaregiverNo, go back to the patient portal
Non-US residents click here.

If you provide additional keywords, you may be able to browse through our database of Scientific Response Documents.

Our scientific content is evidence-based, scientifically balanced and non-promotional. It undergoes rigorous internal medical review and is updated regularly to reflect new information.
Not a healthcare professional? Go to the patient or caregiver website.

PRISTIQ®Clinical Pharmacology (desvenlafaxine succinate)

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The exact mechanism of the antidepressant action of desvenlafaxine is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Non-clinical studies have shown that desvenlafaxine is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI).

12.2 Pharmacodynamics

Desvenlafaxine lacked significant affinity for numerous receptors, including muscarinic-cholinergic, H1-histaminergic, or α1-adrenergic receptors in vitro. Desvenlafaxine also lacked monoamine oxidase (MAO) inhibitory activity.

ECG changes

Electrocardiograms were obtained from 1,492 desvenlafaxine treated patients with major depressive disorder and 984 placebo-treated patients in clinical studies lasting up to 8 weeks. No clinically relevant differences were observed between desvenlafaxine treated and placebo-treated patients for QT, QTc, PR, and QRS intervals. In a thorough QTc study with prospectively determined criteria, desvenlafaxine did not cause QT prolongation. No difference was observed between placebo and desvenlafaxine treatments for the QRS interval.

12.3 Pharmacokinetics

The single-dose pharmacokinetics of desvenlafaxine are linear and dose-proportional in a dose range of 50 to 600 mg (1 to 12 times the recommended approved dosage) per day. With once-daily dosing, steady-state plasma concentrations are achieved within approximately 4 to 5 days. At steady-state, multiple-dose accumulation of desvenlafaxine is linear and predictable from the single-dose pharmacokinetic profile.

Absorption

The absolute oral bioavailability of PRISTIQ after oral administration is about 80%.

Effect of Food

Ingestion of a high-fat meal (800 to 1000 calories) increased desvenlafaxine Cmax about 16% and had no effect on AUC.

Distribution

Steady-state volume of distribution of desvenlafaxine is 3.4 L/kg. Plasma protein binding of desvenlafaxine is 30% and is independent of drug concentration.

Elimination

Metabolism

Desvenlafaxine is primarily metabolized by conjugation (mediated by UGT isoforms) and, to a minor extent, through oxidative metabolism. CYP3A4 mediates the oxidative metabolism (N-demethylation) of desvenlafaxine. The CYP2D6 metabolic pathway is not involved. The pharmacokinetics of desvenlafaxine was similar in subjects with CYP2D6 poor and extensive metabolizer phenotype.

Excretion

Approximately 45% of desvenlafaxine is excreted unchanged in urine at 72 hours after oral administration. Approximately 19% of the administered dose is excreted as the glucuronide metabolite and <5% as the oxidative metabolite (N,O-didesmethylvenlafaxine) in urine.

Specific Populations

No clinically significant differences in the exposures of desvenlafaxine were observed based on ethnicity (White, Black, Hispanic).

The effect of intrinsic patient factors on the pharmacokinetics of desvenlafaxine is presented in Figure 1.

Figure 1 Impact of Intrinsic Factors (Renal, Hepatic Impairment and Population Description) on Desvenlafaxine Pharmacokinetics

Figure 1

Drug Interaction Studies

Clinical Studies

Other Drugs on PRISTIQ

The effect of ketoconazole on the exposures of desvenlafaxine is summarized in Figure 2.

Figure 2. Effect of Other Drugs on Desvenlafaxine Pharmacokinetics
Figure 2

PRISTIQ on Other Drugs

The effects of PRISTIQ on the exposures of other drugs are summarized in Figure 3.

Figure 3. Effects of PRISTIQ on Pharmacokinetics of Other Drugs
Figure 3

In Vitro Studies

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 desvenlafaxine.

Desvenlafaxine does not inhibit CYP1A2, 2A6, 2C8, 2C9, 2C19 CYP2D6, or CYP3A4 isozymes. Desvenlafaxine does not induce CYP3A4 either.

Desvenlafaxine is not a substrate or an inhibitor for the P-glycoprotein (P-gp) transporter.

Did you find an answer to your question? Yes No
Download Prescribing Information
Show All Hide All
Show All Hide All
Did you find an answer to your question? Yes No

Resources

website
Consumer and Patients website
 
website
Pristiq Website for Healthcare Professionals
 
Didn’t find what you were looking for? Contact us.
MI Digital Assistant

Chat online with Pfizer Medical Information regarding your inquiry on a Pfizer medicine.

Call 800-438-1985*

*Contact Medical Information. 9AM-5PM ET Monday to Friday; excluding holidays.

Medical Inquiry

Submit a medical question for Pfizer prescription products.

Report Adverse Event
Pfizer Safety

To report an adverse event related to the Pfizer-BioNTech COVID-19 Vaccine, and you are not part of a clinical trial* for this product, click the link below to submit your information:

Pfizer Safety Reporting Site

*If you are involved in a clinical trial for this product, adverse events should be reported to your coordinating study site.

If you cannot use the above website, or would like to report an adverse event related to a different Pfizer product, please call Pfizer Safety at (800) 438-1985.

FDA Medwatch

You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns either online at https://vaers.hhs.gov or call (800) 822-7967.