Pristiq - Drug Monograph

Introduction

Pristiq (desvenlafaxine) is a serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant approved by the FDA for the treatment of major depressive disorder (MDD). It is the major active metabolite of venlafaxine and is classified as a prescription medication for managing depression in adults.

Mechanism of Action

Desvenlafaxine exerts its therapeutic effects by potently inhibiting the reuptake of both serotonin and norepinephrine in the central nervous system. It has approximately 10 times greater affinity for serotonin transporters compared to norepinephrine transporters. The drug does not significantly inhibit the reuptake of dopamine or have meaningful affinity for muscarinic, histaminergic, or adrenergic receptors.

Indications

• Treatment of major depressive disorder (MDD) in adults

Dosage and Administration

• Renal impairment: Maximum 50 mg daily for moderate impairment; 50 mg every other day for severe impairment
• Hepatic impairment: Maximum 100 mg daily
• Geriatric patients: Use caution; consider lower doses
• Not recommended for use in children

• Tablets should be swallowed whole and not crushed, chewed, or dissolved
• Discontinuation should be gradual to avoid withdrawal symptoms

Pharmacokinetics

Contraindications

• Hypersensitivity to desvenlafaxine, venlafaxine, or any product components
• Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI therapy
• Patients taking linezolid or intravenous methylene blue

Warnings and Precautions

• Serotonin syndrome: Risk especially with other serotonergic drugs
• Elevated blood pressure: Monitor regularly
• Abnormal bleeding: May increase risk of bleeding events
• Angle-closure glaucoma: May precipitate episodes
• Hyponatremia: May occur, especially in elderly patients
• Discontinuation syndrome: Taper gradually when discontinuing
• Mania/hypomania: May occur in patients with bipolar disorder

Drug Interactions

• MAOIs: Contraindicated (risk of serotonin syndrome)
• Other serotonergic drugs: Increased risk of serotonin syndrome
• Drugs that interfere with hemostasis: Increased bleeding risk
• CYP3A4 inhibitors: May increase desvenlafaxine levels
• Drugs metabolized by CYP2D6: Desvenlafaxine may inhibit their metabolism

Adverse Effects

• Nausea (22%)
• Dizziness (13%)
• Hyperhidrosis (10%)
• Constipation (9%)
• Decreased appetite (8%)
• Anxiety (6%)
• Insomnia (6%)

• Suicidal thoughts and behaviors
• Serotonin syndrome
• Seizures
• Angle-closure glaucoma
• Hyponatremia
• Hepatotoxicity
• Interstitial lung disease

Monitoring Parameters

• Blood pressure at baseline and periodically during treatment
• Mental status for emerging suicidality, anxiety, agitation
• Signs and symptoms of serotonin syndrome
• Serum sodium in elderly patients and those on diuretics
• Liver function tests
• Bleeding parameters in patients on anticoagulants
• Weight changes and appetite
• Treatment response using standardized depression scales

Patient Education

• Take medication at the same time each day
• Do not crush, chew, or dissolve tablets
• Report any new or worsening depression symptoms immediately
• Be aware of potential withdrawal symptoms if stopping abruptly
• Avoid alcohol during treatment
• Inform all healthcare providers about Pristiq use before any procedures
• Use caution when driving or operating machinery until effects are known
• Report any unusual bleeding or bruising
• Notify provider if pregnancy is planned or occurs

References

1. FDA Prescribing Information: Pristiq (desvenlafaxine) Extended-Release Tablets 2. Lieberman DZ, et al. J Clin Psychiatry. 2008;69(5):826-832 3. Soares CN, et al. J Clin Psychiatry. 2009;70(4):520-531 4. Thase ME, et al. J Clin Psychiatry. 2009;70(5):706-714 5. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. Third Edition. 2010 6. Micromedex Solutions: Desvenlafaxine Drug Information 7. Lexicomp Online: Desvenlafaxine Monograph