Dosing and uses of Effexor, Effexor XR (venlafaxine)
Adult dosage forms and strengths
tablet
- 25mg
- 37.5mg
- 50mg
- 75mg
- 100mg
tablet, extended release
- 37.5mg
- 75mg
- 150mg
- 225mg
capsule, extended release
- 37.5mg
- 75mg
- 150mg
Depression
Immediate release
- 75 mg/day PO divided q8-12hr initially; may be increased by ≤75 mg/day not faster than every 4 days
- Moderate: Up to 225 mg/day PO divided q8-12hr
- Severe: Up to 375 mg/day PO divided q8-12hr
Extended release
- 37.5-75 mg PO once daily initially; may be increased by 75 mg/day every 4 days; not to exceed 225 mg/day
Generalized Anxiety
Extended release: 37.5-75 mg PO once daily initially; may be increased by 75 mg/day every 4-7 days; not to exceed 225 mg/day
Social Anxiety
Extended release: 75 mg PO once daily
Dosages >75 mg/day not shown to be more effective
Panic Disorder
Extended release: 37.5 mg PO once daily for 7 days, then 75 mg once daily; may be further increased by 75 mg/day every 7 days; not to exceed 225 mg/day
Hot Flashes Due to Hormonal Chemotherapy (Off-label)
Immediate release: 37.5 mg BID or 75 mg qDay; alternatively may titrate up beginning with 37.5 mg qDay for 1 week then 75 mg daily
Extended release: 37.5-150 mg PO once daily for 4-12 weeks
Post-traumatic Stress Disorder (Off-label)
Extended release formulation: 37.5-300 mg/day
Attention Deficit Disorder
18.75-75 mg/day; may increase to 150 mg/day after 4 weeks; doses up to 225 mg/day used
Neuropathic Pain (Off-label)
75-225 mg/day PO ; onset of relief may start in 1-2 weeks or take up to 6 weeks for full benefit
Administration
Take with food
If discontinuing therapy after ≥7 days, taper dosage
Dosing Modifications
Mild to severe renal iumpairment: Reduce dosage by 25-50%
Mild to moderate hepatic impairment: Reduce dosage by 50%
Pediatric dosage forms and strengths
tablet
- 25mg
- 37.5mg
- 50mg
- 75mg
- 100mg
tablet, extended release
- 37.5mg
- 75mg
- 150mg
- 225mg
capsule, extended release
- 37.5mg
- 75mg
- 150mg
Anxiety (Off-label)
Children: 37.5 mg/day PO initially
Adolescents: 37.5-75 mg/day PO initially
Maintenance: Children, 75-150 mg/day; adolescents, 150-300 mg/day
Depression (Off-label)
Children: 37.5 mg/day PO initially
Adolescents: 37.5-75 mg/day PO initially
Maintenance: Children, 75-150 mg/day; adolescents, 150-300 mg/day
Attention Deficit Disorder
<40 kg: 12.5 mg/day PO initially; increase by 12.5 mg/week; not to exceed 50 mg/day divided twice daily
≥40 kg: 12.5 mg/day PO initially; increase by 25 mg/week; not to exceed 75 mg/day divided three times daily
Geriatric dosage forms and strengths
Depression
Immediate release
25-50 mg/day PO divided q8-12hr initially; may be increased as tolerated by ≤25 mg/day no faster than every 4 days
Moderate: Up to 225 mg/day PO divided q8-12hr
Severe: Up to 375 mg/day PO divided q8-12hr
Extended release
37.5 mg PO once daily initially; may be increased by 37.5 mg/day every 4-7 days; not to exceed 225 mg/day
Generalized Anxiety
Extended release: 37.5 mg PO once daily initially; may be increased by 37.5 mg/day every 4 days; not to exceed 225 mg/day
Social Anxiety
Extended release: 37.5 mg PO once daily; may be increased by 37.5 mg/day every 4 days
Panic Disorder
Extended release: 37.5 mg PO once daily for 7 days, then 75 mg once daily; may be further increased by 37.5 mg/day every 7 days; not to exceed 225 mg/day
Effexor, Effexor XR (venlafaxine) adverse (side) effects
>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
Warnings
Black box warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients aged >24 years; slight decrease in suicidal thinking was seen in adults >65 years
Not FDA approved for children; in children and young adults; benefits of taking antidepressants must be weighed against risks
Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
Patient’s family should communicate any abrupt behavioral changes to healthcare provider
Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy
Not FDA approved for treatment of bipolar depression
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, 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 and lactation
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.
Pharmacology of Effexor, Effexor XR (venlafaxine)
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%)
