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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(ven la FAX een)
Generic Available (U.S.)
Yes
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088586.pdf, must be dispensed with this medication.
REMS Components
Tablet, extended release: Medication Guide
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of major depressive disorder, generalized anxiety disorder (GAD), social anxiety disorder (social phobia), panic disorder
Use: Unlabeled/Investigational
Obsessive-compulsive disorder (OCD); hot flashes; neuropathic pain (including diabetic neuropathy); attention attention-deficit/hyperactivity disorder (ADHD); post-traumatic stress disorder (PTSD)
Pregnancy Risk Factor
C
Pregnancy Considerations
Venlafaxine is classified as pregnancy category C due to adverse effects observed in animal studies. Venlafaxine and its active metabolite ODV cross the human placenta. Neonatal seizures and neonatal abstinence syndrome have been noted in case reports following maternal use of venlafaxine during pregnancy. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hyper- or hypotonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. The long-term effects on neurobehavior have not been studied.Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of venlafaxine may be altered. Women should be monitored for decreased efficacy. Women treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued as compared to pregnant women who continue taking antidepressant medications. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. If treatment during pregnancy is required, consider tapering therapy during the third trimester in order to prevent withdrawal symptoms in the infant. If this is done and the woman is considered to be at risk of relapse from her major depressive disorder, the medication can be restarted following delivery, although the dose should be readjusted to that required before pregnancy. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers, 2009).
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Venlafaxine and ODV are found in human milk. Low concentrations of ODV have been found in the serum of nursing infants whose mothers are taking venlafaxine; venlafaxine has also been detected in some infants. Adverse events have not been observed; however, it is recommended to monitor the infant for adverse events if the decision to breast-feed has been made. The long-term effects on neurobehavior have not been studied, thus one should prescribe venlafaxine to a mother who is breast-feeding only when the benefits outweigh the potential risks. The manufacturer does not recommend breast-feeding during therapy.
Contraindications
Hypersensitivity to venlafaxine or any component of the formulation; use of MAO inhibitors within 14 days; should not initiate MAO inhibitor within 7 days of discontinuing venlafaxine
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants in children and teenagers should be dispensed with each prescription. Venlafaxine is not FDA approved for use in children.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Venlafaxine is not FDA approved for the treatment of bipolar depression.
Concerns related to adverse effects:
• Anxiety/insomnia: May cause increase in anxiety, nervousness, and insomnia.
• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin or NSAIDs due to ulcerogenic potential. Data are inconclusive regarding extent of bleeding risk of SNRIs in combination with warfarin or other anticoagulants. Bleeding related to SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
• Hypercholesterolemia: May cause significant increases in serum total cholesterol.
• Hypertension: Dose-related increases in systolic and diastolic blood pressure have been documented. Monitor blood pressure regularly, and if sustained increases noted, consider dose reduction or discontinuation.
• Pulmonary events: Interstitial lung disease and eosinophilic pneumonia have been rarely reported. May present as progressive dyspnea, cough, and/or chest pain. Prompt evaluation and possible discontinuation of therapy may be necessary.
• Serotonin syndrome (SS)/neuroleptic malignant syndrome (NMS)-like reactions: SS and NMS-like reactions have occurred with serotonin/norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) when used alone, and particularly when used in combination with serotonergic agents (eg, triptans) or antidopaminergic agents (eg, antipsychotics). The diagnosis of SS can be made using the Hunter Serotonin Toxicity Criteria (Dunkley, 2003). Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for either syndrome. Discontinue treatment (and any concomitant serotonergic and/or antidopaminergic agents) immediately if signs/symptoms arise.
• Sexual dysfunction: May cause or exacerbate sexual dysfunction.
• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly. Volume depletion and/or concurrent use of diuretics likely increases risk.
• Weight loss and anorectic effects: Dose-dependent weight loss has been observed in both pediatric and adult patients; weight loss was not limited to those experiencing reduced appetite.
Disease-related concerns:
• Cardiovascular disease: May cause sustained increase in blood pressure or tachycardia. Control pre-existing hypertension prior to initiation of venlafaxine. Use caution in patients with recent history of MI, unstable heart disease, or hyperthyroidism. Hypertensive effect is dose related and increases are generally modest (12-15 mm Hg diastolic).
• Hepatic impairment: Use caution; clearance is decreased and plasma concentrations are increased; dosage reduction recommended in patients with mild-to-moderate hepatic impairment.
• Narrow-angle glaucoma: May cause mydriasis; use caution in patients with increased intraocular pressure or at risk of acute narrow-angle glaucoma.
• Renal impairment: Use caution; clearance is decreased and plasma concentrations are increased; dosage reduction recommended in patients with renal impairment.
• Seizure disorders: Use caution with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.
Concurrent drug therapy issues:
• Agents which lower seizure threshold: Concurrent therapy with other drugs which lower the seizure threshold.
• Anticoagulants/antiplatelets: Use caution with concomitant use of NSAIDs, ASA, or other drugs that affect coagulation; the risk of bleeding may be potentiated.
• CNS depressants: Use caution with concomitant therapy.
• MAO inhibitors (MAO-Is): Potential for serotonin syndrome when used with MAO inhibitors; autonomic instability, coma, death, delirium, diaphoresis, hyperthermia, mental status changes/agitation, muscular rigidity, myoclonus, neuroleptic malignant syndrome features, and seizures may occur. Concurrent use with MAO inhibitors is contraindicated. Do not begin venlafaxine within 14 days of terminating MAO-I therapy; do not initiate MAO-I treatment within 7 days of discontinuing venlafaxine.
• Serotonin syndrome/NMS-like reactions: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans), agents which reduce venlafaxine's metabolism, or antidopaminergic agents (including antipsychotics). Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
• Weight loss agents: Agents causing weight loss or anorectic effects should be avoided.
Special populations:
• Pediatrics: Small differences in height and weight have been observed in pediatric patients receiving venlafaxine, particularly those <12 years of age, compared to placebo. Not FDA approved for use in children.
Other warnings/precautions:
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
• Withdrawal syndrome: Abrupt discontinuation or dosage reduction has been associated with a wide range of reactions, including (but not limited to) dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, impaired coordination/balance, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Upon discontinuation of venlafaxine therapy, gradually taper dose. If intolerable symptoms occur following a decrease in dosage or upon discontinuation of therapy, then resuming the previous dose with a more gradual taper should be considered.
Adverse Reactions
Note: Actual frequency may be dependent upon formulation and/or indication
>10%:
Central nervous system: Headache (25% to 38%), somnolence (12% to 26%), dizziness (11% to 24%), insomnia (15% to 24%), nervousness (6% to 21%), anxiety (2% to 11%),
Gastrointestinal: Nausea (21% to 58%), xerostomia (12% to 22%), anorexia (8% to 17%), constipation (8% to 15%)
Genitourinary: Abnormal ejaculation/orgasm (2% to 19%)
Neuromuscular & skeletal: Weakness (8% to 19%)
Miscellaneous: Diaphoresis (7% to 19%)
1% to 10%:
Cardiovascular: Vasodilation (2% to 6%), hypertension (dose related; 3% in patients receiving <100 mg/day, up to 13% in patients receiving >300 mg/day), palpitation (3%), tachycardia (2%), chest pain (2%), postural hypotension (1%), edema
Central nervous system: Yawning (3% to 8%), abnormal dreams (3% to 7%), chills (2% to 7%), agitation (2% to 5%), confusion (2%), abnormal thinking (2%), depersonalization (1%), depression (1% to 3%), fever, migraine, amnesia, hypoesthesia, vertigo
Dermatologic: Rash (3%), pruritus (1%), bruising
Endocrine & metabolic: Libido decreased (2% to 8%), hypercholesterolemia (5%), triglycerides increased
Gastrointestinal: Abdominal pain (8%), diarrhea (8%), vomiting (3% to 8%), dyspepsia (5% to 7%), weight loss (1% to 6%), flatulence (3% to 4%), taste perversion (2%), appetite increased, belching, weight gain
Genitourinary: Impotence (4% to 6%), urinary frequency (3%), urination impaired (2%), urinary retention (1%), metrorrhagia, prostatic disorder, vaginitis
Neuromuscular & skeletal: Tremor (1% to 10%), hypertonia (3%), paresthesia (2% to 3%), twitching (1% to 3%), arthralgia, neck pain, trismus
Ocular: Accommodation abnormal (6% to 9%), abnormal or blurred vision (4% to 6%), mydriasis (2%)
Otic: Tinnitus (2%)
Renal: Albuminuria
Respiratory: Pharyngitis (7%), sinusitis (2%), bronchitis, cough increased, dyspnea
Miscellaneous: Infection (6%), flu-like syndrome (2%), trauma (2%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Agranulocytosis, anaphylaxis, anemia, aneurysm, angina pectoris, angioedema, anuria, aplastic anemia, appendicitis, arrhythmia (including atrial and ventricular tachycardia, fibrillation, and torsade de pointes), arteritis, asthma, ataxia, atelectasis, atrioventricular block, bacteremia, balance/coordination impaired, basophilia, bigeminy, biliary pain, bilirubinemia, bleeding time increased, bradycardia, bradykinesia, BUN increased, bundle branch block, carcinoma, cardiac arrest, cardiovascular disorder (mitral valve and circulatory disturbance), cataract, catatonia, cellulitis, cerebral ischemia, cholelithiasis, congestive heart failure, coronary artery disease, CPK increased, creatinine increased, crystalluria, cyanosis, deafness, DVT, dehydration, delusions, dementia, diabetes mellitus, dystonia, ECG abnormalities (including QT prolongation), embolus, eosinophilia, erythema multiforme, exfoliative dermatitis, extrapyramidal symptoms, extrasystoles, facial paralysis, fasciitis, fatty liver, gastrointestinal ulcer, glaucoma, glycosuria, granuloma, Guillain-Barré syndrome, hematemesis, hematoma, hemorrhage (eye, GI, mucocutaneous, rectal), hepatic necrosis, hepatic failure, hepatitis, homicidal ideation, hostility, hyperacusis, hypercalcinuria, hyperchlorhydria, hyper-/hypoglycemia, hyper-/hypokalemia, hyper-/hypophosphatemia, hyper-/hypothyroidism, hyperuricemia, hypocholesteremia, hyponatremia, hypoproteinemia, hypotension, interstitial lung disease (including eosinophilic pneumonia), intestinal obstruction, jaundice, kidney function abnormal, larynx edema, leukocytosis, leukoderma, leukopenia, liver enzymes increased, loss of consciousness, lymphadenopathy, lymphocytosis, maculopapular rash, menstrual abnormalities, MI, miliaria, moniliasis, multiple myeloma, myasthenia, myoclonus, myopathy, neck rigidity, neuroleptic malignant-like syndrome, neuropathy, neutropenia, osteoporosis, pancreatitis, pancytopenia, peripheral vascular disorder, pleurisy, pneumonia, pyelonephritis, pyuria, renal failure, rhabdomyolysis, rheumatoid arthritis, seizure, serotonin syndrome, SIADH, skin atrophy, Stevens-Johnson syndrome, suicidal ideation (reported at a frequency up to 2% in children/adolescents with major depressive disorder), suicide attempt, syncope, tendon rupture, thrombocythemia, thrombocytopenia, tongue edema, toxic epidermal necrolysis, withdrawal syndrome
Metabolism/Transport Effects
Substrate of CYP2C9 (minor), 2C19 (minor), 2D6 (major), 3A4 (major); Inhibits CYP2B6 (weak), 2D6 (weak), 3A4 (weak)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
Alcohol (Ethyl): May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Specifically, risks of psychomotor impairment may be enhanced. Alcohol (Ethyl) may enhance the hepatotoxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Particularly duloxetine and milnacipran. Management: Patients receiving serotonin/norepinephrine reuptake inhibitors (SNRIs) should be advised to avoid alcohol. Monitor for increased psychomotor impairment and hepatotoxicity in patients who consume alcohol during treatment with SNRIs. Risk D: Consider therapy modification
Alpha-/Beta-Agonists: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Alpha2-Agonists: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine. Risk C: Monitor therapy
Aspirin: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Indinavir: Venlafaxine may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Iobenguane I 123: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
MAO Inhibitors: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylene Blue: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the adverse/toxic effect of Venlafaxine. Specifically, the risk of serotonin syndrome may be increased. Risk C: Monitor therapy
NSAID (Nonselective): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Propafenone: May increase the serum concentration of Venlafaxine. Management: Monitor for increased venlafaxine levels/adverse effects (e.g., hallucinations, agitation, confusion) with propafenone initiation/dose increase. Conversely, monitor for decreased venlafaxine levels with profapenone discontinuation/dose decrease. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
TraZODone: Venlafaxine may enhance the serotonergic effect of TraZODone. This could result in serotonin syndrome. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Venlafaxine may enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Voriconazole: May enhance the adverse/toxic effect of Venlafaxine. Voriconazole may increase the serum concentration of Venlafaxine. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, kava kava, tryptophan (may increase risk of serotonin syndrome and/or excessive sedation).
Storage
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).
Mechanism of Action
Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant activity for muscarinic cholinergic, H1-histaminergic, or alpha2-adrenergic receptors. Venlafaxine and ODV do not possess MAO-inhibitory activity.
Pharmacodynamics/Kinetics
Absorption: Oral: ≥92%; food has no significant effect on absorption or formation of active metabolite
Distribution: Vdss: Venlafaxine 7.5 ± 3.7 L/kg, ODV 5.7 ± 1.8 L/Kg
Protein binding: Venlafaxine 27% ± 2%, ODV 30% ± 12%
Metabolism: Hepatic via CYP2D6 to active metabolite, O-desmethylvenlafaxine (ODV); other metabolites include N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine
Bioavailability: Oral: ~45%
Half-life elimination: Venlafaxine: 5 ± 2 hours; ODV: 11 ± 2 hours; prolonged with cirrhosis (venlafaxine: ~30%, ODV: ~60%), renal impairment (venlafaxine: ~50%, ODV: ~40%), and during dialysis (venlafaxine: ~180%, ODV: ~142%)
Time to peak:
Immediate release: Venlafaxine: 2 hours, ODV: 3 hours
Extended release: Venlafaxine: 5.5 hours, ODV: 9 hours
Excretion: Urine (~87%; 5% of total dose as unchanged drug; 29% of total dose as unconjugated ODV; 26% of total dose as conjugated ODV; 27% of total dose as minor inactive metabolites)
Dosage
Oral:
Children and Adolescents:
Attention-deficit/hyperactivity disorder (unlabeled use; Olvera, 1996): Initial: 12.5 mg/day
Children <40 kg: Increase by 12.5 mg/week to maximum of 50 mg/day in 2 divided doses
Children ≥40 kg: Increase by 25 mg/week to maximum of 75 mg/day in 3 divided doses.
Mean dose: 60 mg or 1.4 mg/kg administered in 2-3 divided doses
Adults:
Depression:
Immediate-release tablets: Initial: 75 mg/day, administered in 2 or 3 divided doses; may increase in ≤75 mg/day increments at intervals of ≥4 days as tolerated (maximum daily dose: 225-375 mg)
Extended-release capsules or tablets: Initial: 37.5-75 mg once daily; in patients who are initiated at 37.5 mg once daily, may increase to 75 mg once daily after 4-7 days; dose may then be increased by ≤75 mg/day increments at intervals of ≥4 days as tolerated (maximum daily dose: 225 mg)
Generalized anxiety disorder: Extended-release capsules: Initial: 37.5-75 mg once daily; in patients who are initiated at 37.5 mg once daily, may increase to 75 mg once daily after 4-7 days; may then be increased by ≤75 mg/day increments at intervals of ≥4 days as tolerated (maximum daily dose: 225 mg)
Panic disorder: Extended-release capsules: Initial: 37.5 mg once daily for 1 week; may increase to 75 mg once daily after 7 days, may then be increased by ≤75 mg/day increments at intervals of ≥7 days (maximum daily dose: 225 mg).
Social anxiety disorder: Extended-release capsules or tablets: 75 mg once daily (maximum daily dose: 75 mg); no evidence that doses >75 mg/day offer any additional benefit
Obsessive-compulsive disorder (unlabeled use): Titrate to usual dosage range of 150-300 mg/day; however, doses up to 375 mg/day have been used; response may be seen in 4 weeks (Phelps, 2005)
Neuropathic pain (unlabeled use): Dosages evaluated varied considerably based on etiology of chronic pain, but efficacy has been shown for many conditions in the range of 75-225 mg/day; onset of relief may occur in 1-2 weeks, or take up to 6 weeks for full benefit (Grothe, 2004).
Diabetic neuropathy (unlabeled use): 75-225 mg/day (Bril, 2011)
Hot flashes (unlabeled use): Doses of 37.5-75 mg/day have demonstrated significant improvement of vasomotor symptoms after 4-8 weeks of treatment; in one study, doses >75 mg/day offered no additional benefit (Evans, 2005; Loprinzi, 2000); however, higher doses (225 mg/day) may be beneficial in patients with perimenopausal depression
Attention-deficit disorder (unlabeled use): Initial: Doses vary between 18.75 to 75 mg/day; may increase after 4 weeks to 150 mg/day; if tolerated, doses up to 225 mg/day have been used (Maidment, 2003)
Post-traumatic stress disorder (PTSD) (unlabeled use): Extended release formulation: 37.5-300 mg/day (Bandelow, 2008; Benedek, 2009)
Note: When discontinuing this medication after more than 1 week of treatment, it is generally recommended that the dose be tapered. If venlafaxine is used for 6 weeks or longer, the dose should be tapered over 2 weeks when discontinuing its use.
Elderly: Alzheimer's dementia-related depression (unlabeled use; Rabins, 2007):
Immediate-release tablets: Initial: 25 mg/day; may increase at weekly intervals to maximum of 375 mg/day in divided doses
Extended-release capsules: Initial: 37.5 mg/day; may increase at weekly intervals to maximum of 225 mg/day
Dosing adjustment in renal impairment:
GFR: 10-70 mL/minute: Reduce total daily dose by 25% to 50%
Hemodialysis: Reduce total daily dose by 50%
Dosing adjustment in hepatic impairment: Mild-to-moderate hepatic impairment: Reduce total daily dose by 50%; further reductions may be necessary in some patients
Administration: Oral
Administer with food.
Extended-release formulations: Swallow capsule or tablet whole; do not crush or chew. Contents of capsule may be sprinkled on a spoonful of applesauce and swallowed immediately without chewing; followed with a glass of water to ensure complete swallowing of the pellets.
Monitoring Parameters
Blood pressure should be regularly monitored, especially in patients with a high baseline blood pressure; may cause mean increase in heart rate of 4-9 beats/minute; cholesterol; mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; height and weight should be monitored in children
Test Interactions
May interfere with urine detection of PCP (false-positive).
Dietary Considerations
Should be taken with food.
Patient Education
It may take 2-3 weeks to achieve desired results. Take with food. Extended release capsules should be swallowed whole; do not crush or chew. Alternatively, contents may be emptied onto a spoonful of applesauce and swallowed without chewing. Avoid alcohol. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience excess drowsiness or insomnia, lightheadedness, dizziness, blurred vision, headache, nausea, vomiting, anorexia, altered taste, dry mouth, constipation, diarrhea, postural hypotension, urinary retention, or sexual dysfunction (reversible). Report persistent CNS effects (eg, insomnia, restlessness, fatigue, anxiety, abnormal thoughts, suicide ideation, confusion, personality changes, impaired cognitive function), muscle cramping or tremors, chest pain, palpitations, rapid heartbeat, swelling of extremities, severe dizziness, unresolved urinary retention, vision changes or eye pain, hearing changes or ringing in ears, skin rash or irritation, or worsening of condition.
Geriatric Considerations
Venlafaxine's low anticholinergic activity, minimal sedation, and hypotension properties makes this a valuable antidepressant in treating elderly with depression or anxiety disorders. No dose adjustment is necessary for age alone; adjust dose for renal function in the elderly. The elderly are more prone to SSRI/SNRI-induced hyponatremia.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation); may contribute to oral discomfort, especially in the elderly; taste perversion. See Effects on Bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Although venlafaxine is not a tricyclic antidepressant, it does block norepinephrine reuptake within CNS synapses as part of its mechanisms. It has been suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way. This is particularly important in patients taking venlafaxine, which has been noted to produce a sustained increase in diastolic blood pressure and heart rate as a side effect.
Mental Health: Child/Adolescent Considerations
Sixteen children and adolescents (mean age: 11.6 years) with attention-deficit/hyperactivity disorder (ADHD) received a mean daily dose of 60 mg (1.4 mg/kg) administered in 2-3 divided doses (Olvera, 1996). Thirty-three children 8-17 years of age with major depression participated in a 6-week trial. For children 8-12 years, doses were initiated at 12.5 mg once daily for 3 days, then increased to 12.5 mg twice daily for 3 days, then increased to 12.5 mg 3 times/day for the rest of the study. Both venlafaxine and placebo patients improved over time, however, no significant differences in symptoms were noted between groups (Mandoki, 1997). Higher initial doses of 37.5 mg/day for 1 week with increases to 75 mg/day for 2-8 weeks are currently being investigated (Weller, 2000). Ten children with autism spectrum disorder were initiated at 12.5 mg/day and adjusted on a flexible basis (mean: 24.4 mg/day; range 6.25-50 mg/day) (Hollander, 2000).
Brent D, Emslie G, Clarke G, et al,“Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents With SSRI-Resistant Depression: The TORDIA Randomized Controlled Trial,” JAMA, 2008, 299(8):901-13.
Hollander E, Kaplan A, Cartwright C, et al, “Venlafaxine in Children, Adolescents, and Young Adults With Autism Spectrum Disorders: An Open Retrospective Clinical Report,” J Child Neurol, 2000, 15(2):132-5.
Mandoki MW, Tapia MR, Tapia MA, et al, “Venlafaxine in the Treatment of Children and Adolescents With Major Depression,” Psychopharmacol Bull, 1997, 33(1):149-54.
Olvera RL, Pliszka SR, Luh J, et al, “An Open Trial of Venlafaxine in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents,” J Child Adolesc Psychopharmacol, 1996, 6(4):241-50.
Weller EB, Weller RA, and Davis HP, “Use of Venlafaxine in Children and Adolescents: A Review of Current Literature,” Depression and Anxiety, 2000, 12(Suppl 1):85-9.
Mental Health: Comment
Venlafaxine functions like an SSRI in low doses (75 mg/day), a dual mechanism agent in moderate doses (150-225 mg/day) and affects serotonin, norepinephrine, and dopamine in high doses (375 mg/day). May cause modest dose related increases in systolic blood pressure; monitor blood pressure.
Nursing: Physical Assessment/Monitoring
Monitor blood pressure and weight/height at beginning of therapy and periodically throughout. Observe for clinical worsening, suicide ideation, or unusual behavior changes, especially during the initial few months of therapy or during dosage changes. Taper dosage when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral: 37.5 mg, 75 mg, 150 mg
Effexor XR®: 37.5 mg, 75 mg, 150 mg
Tablet, oral: 25 mg, 37.5 mg, 50 mg, 75 mg, 100 mg
Effexor®: 50 mg [scored]
Tablet, extended release, oral: 37.5 mg, 75 mg, 150 mg, 225 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Effexor XR)
37.5 mg (30): $129.99
75 mg (90): $409.99
150 mg (30): $159.99
Tablet, 24-hour (Venlafaxine HCl)
37.5 mg (30): $112.99
150 mg (30): $141.62
225 mg (30): $256.98
Tablets (Effexor)
37.5 mg (30): $75.99
50 mg (90): $197.85
75 mg (30): $79.99
100 mg (30): $80.99
Tablets (Venlafaxine HCl)
25 mg (30): $52.99
37.5 mg (30): $53.99
50 mg (100): $189.98
75 mg (30): $59.99
100 mg (100): $190.99
References
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International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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