Trade Names:Effexor- Tablets 37.5 mg- Tablets 50 mg
Trade Names:Effexor XR- Capsules, ER 37.5 mg- Capsules, ER 75 mg- Capsules, ER 150 mg
Trade Names:Venlafaxine- Tablets 25 mg- Tablets 75 mg- Tablets 100 mg- Tablets, ER 37.5 mg- Tablets, ER 75 mg- Tablets, ER 150 mg- Tablets, ER 225 mgNovo-Venlafaxine XR (Canada)
Potentiates norepinephrine, serotonin, and dopamine neurotransmitter activity in the CNS by inhibiting their neuronal reuptake.
Absolute bioavailability is 45% and a single oral dose is well absorbed (at least 92%). Steady-state concentrations of venlafaxine and O-desmethylvenlafaxine (ODV) in plasma are attained within 3 days of oral dosing. Exhibits linear kinetics over dose range of 75 to 450 mg/day. For ER, C max is 150 ng/mL (260 ng/mL for ODV) and T max is 5.5 h (9 h for ODV).
Vd is 7.5 L/kg (5.7 L/kg for ODV); 27% of venlafaxine and 30% of ODV is protein bound.
Extensively metabolized in the liver. The only major metabolite is ODV, which is active.
Renal elimination of venlafaxine and its metabolite is the primary route of excretion. Within 48 h, 87% is recovered in urine. Elimination half-life is 5 h (11 h for ODV).
Dosage adjustment is necessary with CrCl 10 to 70 mL/min. Venlafaxine half-life was prolonged about 50%, and Cl was reduced about 24%; ODV half-life was prolonged 40% although Cl was unchanged.Dialysis
Dose adjustment is necessary. Venlafaxine half-life was prolonged about 180%, and Cl was reduced about 57%. ODV half-life was prolonged about 142%, and Cl was reduced 56%.Hepatic Function Impairment
In patients with hepatic cirrhosis, dosage adjustment is necessary. Venlafaxine half-life was prolonged to about 30%, Cl decreased 50%; ODV half-life was prolonged about 60%, and Cl decreased 30%.Elderly
Pharmacokinetics not altered by age.Gender
Pharmacokinetics not altered by gender.
Treatment of major depressive disorder (MDD).ER capsules, ER tablets
Treatment of social anxiety disorder.ER capsules
Generalized anxiety disorder, panic disorder.
Autism; binge eating disorder; hot flashes; pain; premenstrual dysphoric disorder; posttraumatic stress disorder.
Concomitant use with MAOIs; hypersensitivity to venlafaxine or any component in the formulation.
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 (ER capsules, ER tablets)
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 no less than 4 days (max, 375 mg/day).Generalized Anxiety DisorderAdults (ER capsules)
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 no less than 4 days (max, 225 mg/day).Social Anxiety DisorderAdults (ER tablets, ER capsules)
PO 75 mg daily. There is no evidence that higher doses confer any additional benefit.Panic DisorderAdults (ER capsules)
PO Start with 37.5 mg/day for 7 days as a single dose either in the morning or evening at approximately the same time once daily. After 7 days, the dosage may be increased to 75 mg/day for 7 days. Subsequent dose increases should be in increments of up to 75 mg/day, as needed, and should be made at intervals of no less than 7 days (max, 225 mg/day).Switching From Venlafaxine to Venlafaxine ER
Depressed patients on venlafaxine can be switched to venlafaxine ER at the nearest equivalent total daily dose.Switching Patients To and From MAOIs
When switching from an MAOI to venlafaxine, allow at lease 14 days after discontinuing the MAOI before starting venlafaxine. Allow at least 7 days after discontinuing venlafaxine before starting an MAOI.Hepatic Function ImpairmentAdults
PO Reduce total daily dose by 50% in patients with mild to moderate hepatic function impairment.Renal Function ImpairmentAdults
PO Reduce ER total daily dose by 25% to 50% in patients with renal function impairment (CrCl 10 to 70 mL/min). Reduce total daily dose of immediate-release by 25% in patients with mild to moderate renal function impairment. Reduce total daily dose of ER and immediate-release by 50% in patients undergoing hemodialysis. Withhold dose until dialysis treatment is completed.
Store at controlled room temperature (68° to 77°F). Protect from moisture.ER tablets
Store at 59° to 86°F. Protect from moisture and humidity.
The risk of GI bleeding may be increased.Azole antifungal agents (eg, ketoconazole)
Venlafaxine plasma levels may be elevated, increasing the risk of adverse reactions.Cimetidine
Venlafaxine plasma concentrations may be increased. Caution is advised in patients with hypertension or hepatic function impairment.Clozapine
Plasma levels of clozapine 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.CYP3A4 inhibitors
Venlafaxine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions; use with caution.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 reactions.Indinavir
Plasma concentrations may be decreased by venlafaxine.Linezolid, lithium, methylene blue, metoclopramide, selective 5-HT 1 receptor agonists (eg, sumatriptan), sibutramine, SNRIs, SSRIs, tramadol, trazodone
Serotonin syndrome, including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness, may occur.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.Metoprolol
Coadministration increased metoprolol concentrations by approximately 30% to 40%.Risperidone
Coadministration results in an approximately 32% increase in risperidone AUC.St. John's wort
Increased sedative-hypnotic effects may occur.Sympathomimetics (eg, amphetamine)
Increased sensitivity to sympathomimetics and increased risk of serotonin syndrome.Warfarin
May increase PT, aPT, or INR with coadministration.
None well documented.
Vasodilation (6%); hypertension (5%); palpitation (3%); tachycardia (2%); postural hypotension (1%); deep vein thrombophlebitis, ECG abnormalities (eg, QT prolongation), cardiac arrhythmias (including atrial fibrillation, torsades de pointes) (postmarketing).
Headache (38%); somnolence (26%); dizziness, insomnia (24%); nervousness (21%); asthenia (19%); anxiety (11%); tremor (10%); abnormal dreams (7%); agitation (5%); depression, hypertonia, paresthesia, twitching (3%); abnormal thinking, confusion (2%); amnesia, hypesthesia, migraine, trismus, vertigo (at least 1%); depersonalization (1%); catatonia, delirium, extrapyramidal symptoms, impaired coordination and balance, involuntary movements, NMS-like events, panic, serotonin syndrome, shock-like electrical sensations (postmarketing).
Sweating (19%); rash (3%); pruritus (1%); erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).
Abnormality of accommodation (9%); pharyngitis (7%); abnormal vision (6%); mydriasis, sinusitis, taste perversion, tinnitus (2%); angle-closure glaucoma, eye hemorrhage (postmarketing).
Nausea (58%); dry mouth (22%); anorexia (20%); constipation (15%); abdominal pain, diarrhea, vomiting (8%); dyspepsia (7%); flatulence (4%); eructation (2%); increased appetite (at least 1%); GI bleeding (postmarketing).
Abnormal ejaculation (19%); impotence (10%); decreased libido (9%); impaired urination, orgasm disturbance (8%); anorgasmia (female), urinary frequency (3%); albuminuria, metrorrhagia, prostatitis, urination impaired, vaginitis (at least 1%); urinary retention (1%).
Ecchymosis (at least 1%); agranulocytosis, aplastic anemia, neutropenia, pancytopenia (postmarketing).
Hepatic events (including elevated gamma glutamyltransferase; unspecified LFT abnormalities; liver damage, necrosis, or failure; and fatty liver) (postmarketing).
Increased serum cholesterol (5%); increased CPK and LDH (postmarketing).
Weight loss (4%); edema, weight gain (at least 1%).
Bronchitis, cough increased, dyspnea (at least 1%); interstitial lung disease (postmarketing).
Yawn (8%); chills (7%); flu-like syndrome, infection (6%); accidental injury (5%); chest pain, trauma (2%); arthralgia, fever, neck pain, substernal chest pain (at least 1%); anaphylaxis, congenital anomalies, hemorrhage, increased prolactin, night sweats, pancreatitis, pulmonary eosinophilia, renal failure, rhabdomyolysis, SIADH (postmarketing).
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for MDD and other psychiatric disorders. Appropriately monitor patients of all ages who are started on antidepressant therapy and observe them closely for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with their prescriber.
Monitor 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, and during discontinuation of therapy. Monitor serum cholesterol levels in patients receiving long-term therapy. Monitor BP and heart rate at regular intervals.
Periodically reassess patient to determine need for maintenance treatment and the appropriate dose for such treatment.
Category C . Neonates exposed to venlafaxine late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding.
Excreted in breast milk.
Safety and efficacy not established. Not approved for use in children. Growth rate reduction and weight loss may occur.
Take extra care when increasing dose in elderly patients.
Reduction of dose may be necessary. Use drug with caution.
Reduction of dose may be necessary. Use drug with caution.
May impair judgment, thinking, or motor skills.
Risk of bleeding events, ranging from ecchymosis to life-threatening hemorrhages, may be increased.
Has been reported. Use cautiously in patients with history of mania.
Treatment-emergent anorexia in adults and decreased appetite in children are more common in venlafaxine-treated patients compared with placebo.
Dose-related increases in supine systolic and diastolic BP may occur.
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, heart failure, hyperthyroidism, recent MI).
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.
Mydriasis has been reported. Monitor patients with raised IOP or at risk of acute narrow-angle glaucoma.
Growth rate is decreased in pediatric patients receiving venlafaxine compared with placebo. The differences in observed and expected growth rates were greater in children younger than 12 yr of age compared with children 12 yr of age and older.
Hyponatremia and/or SIADH may occur. Use with caution in elderly, volume-depleted, or diuretic-taking patients.
Because these conditions have been associated with venlafaxine, consider the possibility of these adverse reactions occurring in patients presenting with progressive dyspnea, cough, or chest discomfort.
Treatment-emergent insomnia and nervousness may occur.
Life-threatening NMS may occur.
Screen patients with depression for risk of bipolar disorder prior to initiating therapy with an antidepressant.
Use with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold. Discontinue use if seizures occur.
Potentially life-threatening serotonin syndrome, including mental status changes, may occur.
Serum cholesterol levels increased in patients treated for at least 3 months.
May cause sustained increases in BP.
A loss of 5% or more of body weight has been reported in about 7% of patients.
Bradycardia, bundle branch block, coma, convulsions, death, hypotension, liver necrosis, mydriasis, paresthesia, prolonged QTc interval, rhabdomyolysis, seizures, serotonin syndrome, sinus tachycardia, somnolence, ventricular tachycardia, vertigo, vomiting.
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