• Major depressive disorder.
• Generalized anxiety disorder (Effexor XR only).
• Social anxiety disorder (extended release only).
• Panic disorder (extended release only).

Unlabeled Uses:

• Premenstrual dysphoric disorder.

Contraindicated in:

• Hypersensitivity
• Concurrent use of MAO inhibitors or MAO inhibitor-like drugs (linezolid or methylene blue)
• Lactation: Lactation.

Use Cautiously in:

• Cardiovascular disease, including hypertension
• Hepatic or renal impairment (↓ dose recommended)
• History of seizures or neurologic impairment
• History of mania
• History of drug abuse
• Angle-closure glaucoma
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk (potential for discontinuation syndrome or toxicity in the neonate when venlafaxine is taken during the 3rd trimester)
• Pedi: Safety and effectiveness not established in children; ↑ risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders.

CV: chest pain, hypertension, palpitations, tachycardia.

Derm: ecchymoses, itching, photosensitivity, skin rash.

EENT: rhinitis, visual disturbances, epistaxis, tinnitus.

GI: abdominal pain, altered taste, anorexia, constipation, diarrhea, dry mouth, dyspepsia, nausea, vomiting, weight loss.

GU: ↓libido, delayed/absent orgasm, ejaculatory delay/failure, erectile dysfunction, urinary frequency, urinary retention.

Hemat: BLEEDING.

Neuro: abnormal dreams, anxiety, dizziness, headache, insomnia, nervousness, paresthesia, weakness, abnormal thinking, agitation, confusion, depersonalization, drowsiness, emotional lability, NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, SUICIDAL THOUGHTS, twitching, worsening depression.
Misc: chills, discontinuation syndrome, SEROTONIN SYNDROME, yawning.

Drug-Drug:

• Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions (wait at least 2 wk after stopping MAO inhibitor before initiating venlafaxine; wait at least 1 wk after stopping venlafaxine before starting MAO inhibitors).
• Concurrent use with MAO-inhibitor like drugs, such as linezolid or methylene blue, may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving venlafaxine, immediately discontinue venlafaxine and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume venlafaxine therapy 24 hr after last dose of linezolid or methylene blue)
• Concurrent use with alcohol or other CNS depressants, including sedatives/hypnotics, antihistamines, and opioid analgesics, in depressed patients is not recommended.
• Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans, ↑ risk of serotonin syndrome
• Lithium may have ↑ serotonergic effects with venlafaxine; use cautiously in patients receiving venlafaxine.
• May ↑ levels and the risk of toxicity of desipramine and haloperidol.
• Cimetidine may ↑ the effects of venlafaxine (may be more pronounced in geriatric patients, those with hepatic or renal impairment, or those with pre-existing hypertension).
• Ketoconazole may ↑ the effects of venlafaxine.
• ↑risk of bleeding with NSAIDs, aspirin, clopidogrel, prasugrel, ticagrelor, dabigatran, apixaban, edoxaban, rivaroxaban, or warfarin.

Drug-Natural Products:

• Concomitant use of kava-kava, valerian, chamomile, or hops can ↑ CNS depression.
• ↑risk of serotonergic side effects including serotonin syndrome with St. John’s wort and SAMe.

(Generic available)

• Immediate-release tablets: 25 mg; 37.5 mg; 50 mg; 75 mg; 100 mg;
• Extended-release capsules: 37.5 mg; 75 mg; 150 mg;
• Extended-release tablets: 37.5 mg; 75 mg; 150 mg; 225 mg;

Major Depressive Disorder

• PO (Adults): Tablets: 75 mg/day in 2–3 divided doses; may ↑ by up to 75 mg/day every 4 days, up to 225 mg/day (not to exceed 375 mg/day in 3 divided doses); Extended-release capsules: 75 mg once daily (some patients may be started at 37.5 mg once daily) for 4–7 days; may ↑ by up to 75 mg/day at intervals of not less than 4 days (not to exceed 225 mg/day).

General Anxiety Disorder

• PO (Adults): Extended-release capsules: 75 mg once daily (some patients may be started at 37.5 mg once daily) for 4–7 days; may ↑ by up to 75 mg/day at intervals of not less than 4 days (not to exceed 225 mg/day).

Social Anxiety Disorder

• PO (Adults): Extended-release capsules: 75 mg once daily.

Panic Disorder

• PO (Adults): Extended-release capsules: 37.5 mg once daily for 7 days; may then ↑ to 75 mg once daily; may then ↑ by 75 mg/day every 7 days (not to exceed 225 mg/day).

Effexor, Effexor XR

• Inhibits serotonin and norepinephrine reuptake in the CNS.

• Decrease in depressive symptomatology, with fewer relapses/recurrences.
• Decreased anxiety.Decrease in panic attacks.

Therapeutic Classification: antidepressants, antianxiety agents

Pharmacologic Classification: selective serotonin and norepinephrine reuptake inhibitors-SSNRIs

Absorption: 92–100% absorbed after oral administration.

Distribution: Extensive distribution into body tissues.

Metabolism/Excretion: Extensively metabolized on first pass through the liver (primarily through the CYP2D6 isoenzyme); the CYP2D6 isoenzyme exhibits genetic polymorphism (7% of population may be poor metabolizers and may have significantly ↑ venlafaxine concentrations and an ↑ risk of adverse effects). One metabolite, O-desmethylvenlafaxine (ODV), has antidepressant activity. 5% of venlafaxine is excreted unchanged in urine; 30% of the active metabolite is excreted in urine.

Half-life: Venlafaxine: 3–5 hr; ODV: 9–11 hr (both are ↑ in hepatic/renal impairment).

(antidepressant action)

• Instruct patient to take venlafaxine as directed at the same time each day. Take missed doses as soon as possible unless almost time for next dose. Do not double doses or discontinue abruptly. Patients taking venlafaxine for >6 wk should have dose gradually decreased before discontinuation to prevent dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis; discontinuation may take several mo.
• Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide; new or worse depression or anxiety; agitation or restlessness; panic attacks; insomnia; new or worse irritability; aggressiveness; acting on dangerous impulses, mania, or other changes in mood or behavior or if symptoms of serotonin syndrome occur.
• May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to the drug is known.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Caution patient to avoid taking alcohol or other CNS-depressant drugs, including opioids, during therapy.
• Instruct patient to notify health care professional if signs of allergy (rash, hives) occur.
• Inform patient that venlafaxine may cause symptoms of sexual dysfunction. In males, ejaculatory delay or failure, decreased libido, and erectile dysfunction may occur. In female patients, may result in decreased libido and delayed or absent orgasm. Advise patient to notify health care professional if symptoms occur.
• Advise females of reproductive potential to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. Use during last month of pregnancy increases risk of postpartum hemorrhage. If used during pregnancy, should be tapered during 3rd trimester to avoid neonatal serotonin syndrome. Monitor infants exposed to venlafaxine for excess sedation, restlessness, agitation, poor feeding, poor weight gain, respiratory distress; may ↑ risk of persistent pulmonary hypertension of the newborn. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at womensmentalhealth.org/research/pregnancyregistry/antidepressants/.
• Emphasize the importance of follow-up exams to monitor progress.

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