A-Z Drug Facts > Venlafaxine

Venlafaxine

Pronouncation: (VEN-luh-fax-EEN)
Class: Serotonin and norepinephrine reuptake inhibitor

Trade Names:
Effexor
- Tablets 25 mg
- Tablets 37.5 mg
- Tablets 50 mg
- Tablets 75 mg
- Tablets 100 mg

Trade Names:
Effexor XR
- Capsules, extended-release 37.5 mg
- Capsules, extended-release 75 mg
- Capsules, extended-release 150 mg

Pharmacology

Potentiates norepinephrine, serotonin, and dopamine neurotransmitter activity in the CNS by inhibiting their neuronal reuptake.

Pharmacokinetics

Absorption

Absolute bioavailability is 45% and well absorbed (at least 92%) of single oral dose. Steady-state concentrations of venlafaxine and O-desmethylvenlafaxine (ODV) in plasma are attained within 3 days of oral dose. Exhibits linear kinetics over dose range 75 to 450 mg/day.

Distribution

Vd is 7.5 L/kg (5.7 L/kg for ODV); 27% venlafaxine and 30% ODV is protein bound.

Metabolism

Extensively metabolized in the liver. The only major metabolite is ODV, which is active.

Elimination

Renal elimination of venlafaxine and its metabolite is the primary route of excretion. Within 48 h, 87% is recovered in urine. Elimination t _½ is 5 h (11 h for ODV).

Special Populations

Renal Function Impairment

Dosage adjustment is necessary with CrCl 10 to 70 mL/min. Venlafaxine t _½ was prolonged about 50%, Cl was reduced about 24%; ODV t _½ was prolonged 40% although Cl was unchanged.

Hepatic Function Impairment

In patients with hepatic cirrhosis, dosage adjustment is necessary. Venlafaxine t _½ was prolonged to about 30%, Cl decreased 50%; ODV t _½ was prolonged about 60%, Cl decreased 30%.

Dialysis

Dose adjustment is necessary. Venlafaxine t _½ was prolonged about 180%, and Cl was reduced about 57%. ODV t _½ was prolonged about 142%, and Cl was reduced 56%.

Indications and Usage

Effexor , Effexor XR

Treatment of major depressive disorder.

Effexor XR

Treatment of generalized anxiety disorder; treatment of social anxiety disorder.

Contraindications

Concomitant use with MAOIs; hypersensitivity to venlafaxine or any component in the formulation.

Dosage and Administration

Major Depressive Disorder
Adults (immediate-release)

PO 75 mg/day in 2 or 3 divided doses; titrate to clinical effect, adding up to 75 mg/day at intervals of at least 4 days (max, 375 mg/day).

Adults (extended-release)

PO 75 mg/day administered as single dose either in the morning or evening at approximately same time once daily. Some patients may need to start at 37.5 mg/day for 4 to 7 days before increasing to 75 mg/day. Titrate to clinical effect, in increments of up to 75 mg/day at intervals of not less than 4 days (max, 375 mg/day).

Generalized Anxiety Disorder/Social Anxiety Disorder
Adults (extended-release)

PO 75 mg/day administered as single dose either in the morning or evening at approximately same time once daily. Some patients may need to start at 37.5 mg/day for 4 to 7 days before increasing to 75 mg/day. Titrate to clinical effect, in increments of up to 75 mg/day at intervals of not less than 4 days (max, 225 mg/day).

Hepatic Function Impairment
Adults

PO Reduce total daily dose 50% in patients with moderate hepatic impairment.

Renal Function Impairment
Adults

PO Reduce venlafaxine extended-release total daily dose 25% to 50% in patients with renal impairment (CrCl 10 to 70 mL/min). Reduce total daily dose of venlafaxine immediate‐release 25% in patients with mild to moderate renal impairment. Reduce total daily dose 50% in patients undergoing hemodialysis. Withhold dose until dialysis treatment is completed.

General Advice

• Depressed patients on venlafaxine can be switched to venlafaxine extended-release at the nearest equivalent total daily dose.
• Administer with food.
• Swallow venlafaxine extended-release capsules whole. Do not separate, crush, or chew.
• For patients who have difficulty swallowing venlafaxine extended-release capsules whole, the capsules may be opened and the contents sprinkled on a spoonful of applesauce. The drug/applesauce mixture should be swallowed immediately without chewing and followed with a glass of water. Do not prepare the mixture ahead of time and store.

Storage/Stability

Store at controlled room temperature (68° to 77°F). Protect from moisture.

Drug Interactions

Cimetidine

Venlafaxine plasma concentrations may be increased. Caution is advised in patients with hypertension or hepatic dysfunction.

Clozapine

Plasma levels may be increased.

CNS-active drugs (eg, serotonin reuptake inhibitors [eg, fluoxetine] lithium)

Because this interaction has not been studied, caution is warranted when coadministering these agents with venlafaxine.

Cyproheptadine

Decreased pharmacologic effects of venlafaxine may occur.

Desipramine, haloperidol

Plasma levels of these drugs may be elevated by venlafaxine, increasing the risk of adverse effects.

Indinavir

Plasma concentrations may be decreased by venlafaxine.

MAOIs

MAOIs have produced serious, even fatal, reactions when given concomitantly with venlafaxine. Do not use venlafaxine together with MAOIs or within 14 days of MAOI use. Wait at least 7 days after stopping venlafaxine before using MAOIs.

St. John's wort

Increased sedative-hypnotic effects may occur.

Sibutramine, sumatriptan, tramadol, trazodone

Serotonin syndrome, including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.

Warfarin

May increase PT, aPT, or INR with coadministration.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Vasodilation (6%); hypertension (5%); palpitation (3%); tachycardia (2%); postural hypotension (1%); deep vein thrombophlebitis, EKG abnormalities (eg, QT prolongation), cardiac arrhythmias (including atrial fibrillation, torsades de pointes [postmarketing]).

CNS

Headache (34%); somnolence (26%); dizziness (24%); insomnia (23%); nervousness (21%); asthenia (17%); anxiety (11%); tremor (10%); abnormal dreams (7%); agitation (5%); depression, hypertonia, paresthesia (3%); twitching, abnormal thinking, confusion (2%); depersonalization (1%); migraine, trismus, vertigo, amnesia, hypesthesia (at least 1%); catatonia, delirium, extrapyramidal symptoms, neuroleptic malignant syndrome-like events, involuntary movements, serotonin syndrome, shock-like electrical sensations, panic (postmarketing).

Dermatologic

Sweating (19%); rash (3%); pruritus (1%); epidermal necrolysis/Stevens-Johnson syndrome, erythema multiforme (postmarketing).

EENT

Abnormality of accommodation (9%); pharyngitis (7%); abnormal vision (6%); mydriasis, taste perversion, tinnitus, sinusitis (2%); angle-closure glaucoma (postmarketing).

GI

Nausea (58%); dry mouth (22%); anorexia (20%); constipation (15%); diarrhea, vomiting, abdominal pain (8%); dyspepsia (7%); flatulence (4%); eructation (2%); increased appetite (at least 1%).

Genitourinary

Abnormal ejaculation (16%); impotence (10%); decreased libido (9%); impaired urination, orgasm disturbance (8%); anorgasmia (female), urinary frequency (3%); urinary retention (1%); metrorrhagia, prostatitis, vaginitis (at least 1%).

Hematologic

Ecchymosis (at least 1%); agranulocytosis, aplastic anemia, neutropenia, pancytopenia (postmarketing).

Hepatic

Hepatic events (including elevated GGT, unspecified LFT abnormalities, liver damage necrosis, failure and fatty liver [postmarketing]).

Lab Tests

Increased serum cholesterol (5%); increased CPK and LDH (postmarketing).

Metabolic-Nutritional

Weight loss (4%); weight gain, edema (at least 1%).

Respiratory

Dyspnea, cough increased, bronchitis (at least 1%).

Miscellaneous

Yawn (8%); chills (7%); infection, flu-like syndrome (6%); accidental injury (5%); chest pain, trauma (2%); arthralgia, fever, neck pain (at least 1%); congenital anomalies, night sweats, pancreatitis, hemorrhage, anaphylaxis, renal failure, rhabdomyolysis, pulmonary eosinophilia, increased prolactin, SIADH (postmarketing).

Precautions

Warnings Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder and other psychiatric disorders. When considering the use of any antidepressant in a child or adolescent balance this risk with clinical need. Closely observe children or adolescents for clinical worsening, suicidality, or unusual changes in behavior during the initial few months of therapy or at times of dose changes, either increases or decreases. Advise families and caregivers of the need for close observation and communication with the prescriber.

Monitor Monitor pediatric and adult patients for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy or at times of dose changes, either increases or decreases. Evaluate pediatric patients at least weekly with face-to-face contact with the patient or their family members or caregiver during the first 4 wk of therapy, then every other week for the next 4 wk, then at 12 wk, and as clinically indicated thereafter.

Pregnancy

Category C . Neonates exposed to venlafaxine late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding.

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established. Growth rate reduction may occur.

Elderly

Take extra care when increasing dose in elderly patients.

Renal Function

Reduction of dose may be necessary. Use drug with caution.

Hepatic Function

Reduction of dose may be necessary. Use drug with caution.

Hazardous Tasks

May impair judgment, thinking, or motor skills.

Activation of mania/hypomania

Has been reported. Use cautiously in patients with history of mania.

Concomitant illness

Use with caution in patients with diseases or conditions that could affect hemodynamic responses or metabolism and whose underlying medical conditions might be compromised by increases in heart rate (eg, hyperthyroidism, heart failure, recent MI).

Discontinuation of treatment

If treatment is to be discontinued, or the dose reduced, after more than 1 wk of therapy, gradually taper the dose and monitor patient for withdrawal symptoms. If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.

Hyponatremia

Hyponatremia and/or SIADH may occur. Use with caution in elderly, volume-depleted, or diuretic-taking patients.

Screening for bipolar disorder

Screen patients with depression for risk of bipolar disorder prior to initiating therapy with an antidepressant.

Seizures

Use with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold. Discontinue use if seizures occur.

Sustained hypertension

May cause sustained increases in BP.

Overdosage

Symptoms

Somnolence, sinus tachycardia, generalized convulsions, QTc prolongation.

Patient Information

• Advise patient or caregiver to read patient information leaflet before starting therapy and with each refill.
• If patient is a child or adolescent being treated for depression, advise patient, family, or caregiver to read the Medication Guide About Using Antidepressants in Children and Teenagers before starting therapy and with each refill. Review face-to-face monitoring schedule required for use of drug in this situation.
• Advise patient that dose will be started low and then increased until maximum benefit is obtained.
• Instruct patient to take prescribed dose with food.
• Advise patient using venlafaxine extended-release capsules to swallow capsules whole. Caution patient not to separate, crush, or chew the capsules.
• Advise patient who has difficulty swallowing venlafaxine extended-release capsules whole, that the capsules may be opened and the contents sprinkled on a spoonful of applesauce. The drug/applesauce mixture should be swallowed immediately without chewing and followed with a glass of water. Caution patient not to prepare the mixture ahead of time and store.
• Advise patient that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up and to never take 2 doses at the same time.
• Instruct patient not to change the dose or stop taking unless advised by health care provider.
• Instruct patient not to stop taking the medication when they feel better.
• Caution patient that unless advised by health care provider, not to take aspirin or aspirin-containing products, NSAIDS, Ginkgo biloba , or any other medication or herb that can affect coagulation because of increased risk of serious bleeding.
• Instruct patient to contact health care provider if symptoms do not appear to be getting better, are getting worse, or if bothersome side effects (eg, excessive drowsiness, diarrhea, tremors, nausea, diarrhea, nervousness, changes in sexual function) occur.
• Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Advise patient, family, or caregiver to notify health care provider if rash, hives, or other symptoms of an allergic reaction develop.
• Advise patient, family, or caregiver of patient being treated for depression to be alert for abnormal changes in mood or thinking and to immediately report any of the following to health care provider: change in personality; change in mood; anxiety; agitation; panic attacks; insomnia; irritability; hostility or aggressiveness; impulsivity; akathisia (psychomotor restlessness); suicidal thoughts or behavior. Advise families and caregivers of patients to observe for emergence on a day-to-day basis, as changes may be abrupt.
• Advise patient that if medication needs to be discontinued it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
• Instruct patient to avoid alcoholic beverages and sedatives or depressants (eg, diazepam) while taking medication.
• Advise patient with high BP to monitor BP at regular intervals.
• Advise patient that drug may impair judgment, thinking, or motor skills, or cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.

Link to this page

Printable Version

Email Page

Add to my drug list