venlafaxine

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).

Time/Action Profile ⬆ ⬇

(antidepressant action)

ROUTE	ONSET	PEAK	DURATION
PO	within 2 wk	2–4 wk	unknown

Contraind./Precautions ⬆ ⬇

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.

Adv. Reactions/Side Effects ⬆ ⬇

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

Interactions ⬆ ⬇

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.

Route/Dosage ⬆ ⬇

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).

Renal Impairment

PO (Adults ): CCr 10–70 mL/min:↓ daily dose by 25% (immediate release); CCr 30–89 mL/min:↓ daily dose by 25–50% (extended release); CCr <30 mL/min:↓ daily dose by ≥50% (extended release); Hemodialysis:↓ daily dose by ≥50%.

Hepatic Impairment

PO (Adults ): Mild, moderate, or severe hepatic impairment:↓ daily dose by 50%.

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).

Renal Impairment

PO (Adults ): CCr 10–70 mL/min:↓ daily dose by 25% (immediate release); CCr 30–89 mL/min:↓ daily dose by 25–50% (extended release); CCr <30 mL/min:↓ daily dose by ≥50% (extended release); Hemodialysis:↓ daily dose by ≥50%.

Hepatic Impairment

PO (Adults ): Mild, moderate, or severe hepatic impairment:↓ daily dose by 50%.

Social Anxiety Disorder

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

Renal Impairment

PO (Adults ): CCr 10–70 mL/min:↓ daily dose by 25% (immediate release); CCr 30–89 mL/min:↓ daily dose by 25–50% (extended release); CCr <30 mL/min:↓ daily dose by ≥50% (extended release); Hemodialysis:↓ daily dose by ≥50%.

Hepatic Impairment

PO (Adults ): Mild, moderate, or severe hepatic impairment:↓ daily dose by 50%.

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).

Hepatic Impairment

PO (Adults ): Mild, moderate, or severe hepatic impairment:↓ daily dose by 50%.

Renal Impairment

PO (Adults ): CCr 10–70 mL/min:↓ daily dose by 25% (immediate release); CCr 30–89 mL/min:↓ daily dose by 25–50% (extended release); CCr <30 mL/min:↓ daily dose by ≥50% (extended release); Hemodialysis:↓ daily dose by ≥50%.

Availability ⬆ ⬇

(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

Assessment ⬆ ⬇

Screen patients for a personal or family history of bipolar disorder, mania, or hypomania before starting therapy.
Assess mental status and mood changes. Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
Assess suicidal tendencies, especially in early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yr.
Monitor BP before and periodically during therapy. Sustained hypertension may be dose-related; decrease dose or discontinue therapy if this occurs.
Monitor appetite and nutritional intake. Weigh weekly. Report continued weight loss. Adjust diet as tolerated to support nutritional status.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyper-reflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
Assess sexual function before starting venlafaxine. Assess for changes in sexual function during treatment, including timing of onset; patient may not report.

Lab Test Considerations:

Monitor CBC with differential and platelet count periodically during therapy. May cause anemia, leukocytosis, leukopenia, thrombocytopenia, basophilia, and eosinophilia.
- May cause an ↑ in serum alkaline phosphatase, bilirubin, AST, ALT, BUN, and creatinine.
- May also cause ↑ serum cholesterol.
- May cause electrolyte abnormalities (hyperglycemia or hypoglycemia, hyperkalemia or hypokalemia, hyperuricemia, hyperphosphatemia or hypophosphatemia, and hyponatremia).
- May cause false-positive immunoassay screening tests for phencyclidine and amphetamine.

Implementation ⬆ ⬇

Do not confuse Effexor XR (venlafaxine) with Enablex (darifenacin).
PO: Administer venlafaxine with food.
- DNC: Swallow extended-release capsules and tablets whole; do not crush, break, or chew.
- Extended-release capsules may be opened and contents sprinkled on a spoonful of applesauce. Take immediately and follow with a glass of water. Do not store mixture for later use.

Patient/Family Teaching ⬆ ⬇

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.
Rep: 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 https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/.
Emphasize the importance of follow-up exams to monitor progress.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

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