venlafaxine (Rx)

>10%

Headache (25-38%)

Nausea (21-58%)

Insomnia (15-24%)

Asthenia (16-20%)

Dizziness (11-24%)

Ejaculation disorder (2-19%)

Somnolence (12-26%)

Dry mouth (12-22%)

Diaphoresis (7-19%)

Anorexia (15-17%)

Nervousness (17-26%)

Anorgasmia (5-13%)

1-10%

Weight loss (1-6%)

Abnormal vision (4-6%)

Hypertension (2-5%)

Impotence (4-6%)

Paresthesia (2-3%)

Tremor (1-10%)

Vasodilation (2-6%)

Vomiting (3-8%)

Weight gain (2%)

Flatulence (3-4%)

Pruritus (1%)

Yawning (3-8%)

Dyspepsia (5-7%)

Twitching (1-3%)

Mydriasis (2%)

<1%

Angioedema

Agranulocytosis

Anemia

Anuria

Aneurism

Bacteremia

Myasthenia

Syncope

Suicide ideation/attempt

Postmarketing Reports

Chills

Dyspnea

Interstitial lung disease

Takotsubo cardiomyopathy

Anaphylaxis

Catatonia

Impaired coordination and balance

Deep vein thrombophlebitis

Delirium

Contraindications

Hypersensitivity

Coadministration with serotonergic drugs

• Coadministration with monoamine oxidase inhibitors (MAOIs)
• Concomitant MAOIs administration within 14 days before initiating venlafaxine or within 7 days after discontinuing venlafaxine
• Initiation of venlafaxine in patient being treated with linezolid or IV methylene blue

Cautions

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

Use caution in bipolar mania, history of seizures, and cardiovascular disease

May precipitate mania or hypomania episodes in patients with bipolar disorder; avoid monotherapy in bipolar disorder; screen patients presenting with depressive symptoms for bipolar disorder

Use caution in hepatic or renal impairment

Neonates exposed to serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding

Clinical worsening and suicidal ideation may occur despite medication in adolescents and young adults (18-24 years)

When discontinuing, taper dosage to avoid flulike symptoms

May cause increase in nervousness, anxiety, or insomnia

May impair ability to operate heavy machinery; depresses CNS

Bone fractures reported with antidepressant therapy; consider possibility if patient experiences bone pain

May cause significant increase in serum cholesterol

Dose-dependent anorectic effects and weight loss reported in children and adult patients

Dose-related increase in systolic and diastolic pressure reported

Eosinophilic pneumonia and interstitial lung disease reported

SAIDH and hyponatremia reported SSRIs

Potentially life-threatening serotonin syndrome with SSRIs and SNRIs when used in combination with other serotonergic agents including TCAs, buspirone tryptophan, fentanyl, tramadol, lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and triptans; symptoms 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

Venlafaxine in patient being treated with linezolid or IV methylene blue increases risk of serotonin syndrome; if linezolid or IV methylene blue must be administered, discontinue venlafaxine immediately and monitor for central nervous system (CNS) toxicity; therapy may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk

Control hypertension before initiating treatment; monitor blood pressure regularly during treatment

Risks of sustained hypertension, hyponatremia, and impeded height and weight in children

Drug-laboratory test interactions: False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been observed during venlafaxine therapy because of lack of specificity of the screening tests

May cause or exacerbate sexual dysfunction

Pregnancy category: C

Lactation: Enters milk; not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

"Bicyclic" antidepressant; drug is structurally unrelated to SSRIs, MAOIs, and tricyclic antidepressants (TCAs), but it and its metabolite are potent inhibitors of serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake; it does not have MAOI activity or activity for H1 histaminergic, muscarinic cholinergic, or alpha2-adrenergic receptors

Absorption

Absorption: 92%

Bioavailability: 45%

Peak plasma time: 2-3 hr (immediate release); 5.5-9 hr (extended release)

Concentration: Immediate release, 225-290 ng/mL; extended release, 150-260 ng/mL

Distribution

Protein bound: 27-30%

Vd: Immediate release, 7.5 L/kg

Metabolism

Metabolized in liver by CYP2D6

Metabolites: O-desmethylvenlafaxine

Enzymes inhibited: CYP2D6 (weak)

Elimination

Half-life: 5-11 hr (prolonged in renal or hepatic dysfunction)

Dialyzable: No

Excretion: Urine (87%)