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venlafaxine (Effexor XR)

Tradename: Effexor XR. Indications: 1) treatment of depression* & depressive disorders 2) treatment of panic disorder [22] 3) post traumatic stress disorder (PTSD) 4) hot flashes secondary to anti-estrogen or anti-androgen therapy [5] * on list of drugs to avoid for treatment of depression [20] - risk of cardiovascular disease cited Contraindications: 1) concurrent administration of MAO inhibitors 2) caution in patients with hypertension 3) < 18 years of age; risk of suicidal ideation [9,10] Dosage: 1) start 75 mg PO daily divided BID or TID 2) increase by 75 mg daily at weekly intervals 3) max 225-375 mg/day 4) decrease dose by 25-50% with renal impairment 5) do NOT stop abruptly 5) Effexor XR: QD Tabs: 25, 37.5, 50, 75, 100 mg. (also capsules) [13] Effexor XR: capsules 37.5, 75 & 150 mg [16] Dosage adjustment in renal failure: 1) creatinine clearance 10-70 mL/min: decrease dose by 25% 2) renal dialysis: decrease dose by 50%; give dose after dialysis Dosage adjustment for hepatic insufficiency: - administer 50% of dose Pharmacokinetics: 1) sustained release is achieved by slow diffusion through the coating membrane of spheroids 2) well absorbed orally (92%) 3) minimal protein binding (27-30%) 4) metabolized in liver by cyt P450 2D6 5) elimination 1/2life a) 3-7 hours [4]; 45 hours with chronic dosing b) active metabolite desvenlafaxine 1/2life 11-13 hours [4]; 150 hours with chronic dosing 6) eliminated in urine 7) steady state is achieved in 3-14 days 8) onset of activity may take several weeks Adverse effects: 1) common (> 10%) - nausea (37%), headache (25%), somnolence (23%), dizziness (19%), insomnia (18%), constipation (13%), sexual dysfunction (12%), weakness (12%), sweating (12%), anorexia (11%) 2) less common (1-10%) - nervousness, hypertension, anxiety, tremor, vomiting, dry mouth, blurred vision, malaise, neck pain, migraine, dysphagia, ecchymosis, peripheral edema, weight gain, bronchitis, dyspnea, dysuria, hematuria, impaired urination, vaginitis, menorrhagia, ear pain 3) other - increased risk of cardiovascular disease [20] - hypertension, sustained (dose-related, 3-13%); - higher doses may cause increases diastolic blood pressure - may increase heart rate - diarrhea [3] - somnolence - abnormal ejaculation - abnormal dreams - hyponatremia [8] - may be withdrawal syndrome/hypotension with abrupt discontinuation (do NOT stop abruptly) - venlafaxine exacerbates restless legs syndrome [18] - venlafaxine exacerbates periodic limb movment disorder [18] - no substantial increase in prevalence of overall cardiac birth defects when taken during the 1st trimester of pregnancy [19] - may impair platelet function [18] Drug interactions: 1) concurrent administration of cimetidine decreases clearance of venlafaxine (43%) 2) haloperidol 3) MAO inhibitors: contraindicated; may cause hypertension, tachycardia, seizures, death; separate by 2 week washout 4) selegiline: in combination increases risk of serotonin syndrome 5) SSRI: in combination increases risk of serotonin syndrome 6) clonidine: decreased central hypotensive effects 7) potential increased toxicity with: - tricyclic antidepressants (TCA), fluoxetine, sertraline, phenothiazines, class 1C antiarrhythmic agents, some beta blockers 8) any drug that inhibits cyt P450 2D6 may increase level of venlafaxine 9) alcohol can increase adverse effects of venlafaxine [12] 10) may increase risk of bleeding when used in combination with warfarin [18] Laboratory: - may increase plasma metanephrine & plasma normetanephrine [21] Mechanism of action: 1) inhibits reuptake of serotonin (> norepinephrine [11]) 2) inhibits reuptake of norepinephrine (< serotonin [11]) 3) weakly inhibits dopamine reuptake

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6) desvenlafaxine; norvenlafaxine; N-desmethylvenlafaxine (Pristiq)

General

serotonin & norepinephrine reuptake inhibitor (SNRI, dual-acting reuptake inhibitor)

Properties

MISC-INFO: elimination route KIDNEY pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Wyeth-Ayerst package insert
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Prescriber's Letter 7(2):11, Feb. 2000
  6. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  7. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  8. Prescriber's Letter 9(8):38 2002
  9. Prescriber's Letter 10(10):57 2003 Detail-Document#: 191003 (subscription needed) http://www.prescribersletter.com
  10. Journal Watch 24(11):85, 2004 Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet. 2004 Apr 24;363(9418):1341-5. Review. PMID: 15110490 - Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. Efficacy and safety of antidepressants for children and adolescents. BMJ. 2004 Apr 10;328(7444):879-83. Review. No abstract available. Erratum in: BMJ. 2004 May 15;328(7449):1170. PMID: 15073072 http://bmj.bmjjournals.com/cgi/content/full/328/7444/879
  11. Prescriber's Letter 11(9): 2004 Detail-Document#: 200901 (subscription needed) http://www.prescribersletter.com
  12. FDA Medwatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Effexor
  13. Prescriber's Letter 16(1): 2009 COMMENTARY: New Venlafaxine Extended-Release Formulation LETTER: New Venlafaxine Extended-Release Formulation Detail-Document#: 250108 (subscription needed) http://www.prescribersletter.com
  14. Prescriber's Letter 16(2): 2009 Comparison of Venlafaxine and Desvenlafaxine (Pristiq) Detail-Document#: 250202 (subscription needed) http://www.prescribersletter.com
  15. FDA NEWS RELEASE: June 29, 2010 FDA Approves First Generic Effexor Extended Release Capsules to Treat Major Depressive Disorder http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm217624.htm
  16. Effexor EX Prescribing Information http://www.wyeth.com/content/showlabeling.asp?id=100
  17. Prescriber's Letter 17(8): 2010 CHART: Comparison of Venlafaxine and Desvenlafaxine CHART: State Regulations on Generic Substitution Detail-Document#: 260802 (subscription needed) http://www.prescribersletter.com
  18. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010 - Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  19. Furu K et al Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ. 2015 Apr 17;350:h1798 PMID: 25888213
  20. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  21. NEJM Knowledge+ Question of the Week. December 18, 2018 https://knowledgeplus.nejm.org/question-of-week/803/
  22. NEJM Knowledge_ Question of the Week. Oct 28, 2020 https://knowledgeplus.nejm.org/question-of-week/1827/