Venlafaxine

From Anvita Health Wiki

Contents 1 Introduction 2 Contraindications 3 Dosage 4 Dosage-adjustment-in-renal-failure 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 More General Terms 10 Additional Terms 11 Internet Database 12 References

Introduction

• Tradename: Effexor XR. Indictations:
• treatment of depressive disorders
• post traumatic stress disorder ( PTSD)
• hot flashes secondary to anti- estrogen or anti- androgen therapy [5]

Contraindications

• concurrent administration of MAO inhibitors
• caution in patients with hypertension
• < 18 years of age; risk of suicidal ideation [9,10]
  

• pregnancy category = c
• safety in lactation = ?

Dosage

• start 75 mg PO daily divided BID or TID
• increase by 75 mg daily at weekly intervals
• max 225-375 mg/day
• decrease dose by 25-50% with renal impairment
• do NOT stop abruptly
• 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

• creatinine clearance 10-70 mL/min: decrease dose by 25%
• dialysis: decrease dose by 50%; give dose after dialysis Dosage adjustment for hepatic insufficiency:

• administer 50% of dose

Pharmacokinetics

• sustained release is achieved by slow diffusion through the coating membrane of spheroids
• well absorbed orally (92%)
• minimal protein binding (27-30%)
• metabolized in liver by cyt P450 2D6
• elimination 1/2life

• 3-7 hours [4]; 45 hours with chronic dosing
• active metabolite desvenlafaxine 1/2life 11-13 hours [4]; 150 hours with chronic dosing

• eliminated in urine
• steady state is achieved in 3-14 days
• onset of activity may take several weeks
  

• elimination via kidney

Adverse-effects

• common (> 10%)

• nausea (37%), headache (25%), somnolence (23%), dizziness (19%), insomnia (18%), constipation (13%), sexual dysfunction (12%), weakness (12%), sweating (12%), anorexia (11%)

• 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

• other

• 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]
  
• drug adverse effects of antidepressants

Drug-interactions

• concurrent administration of cimetidine decreases clearance of venlafaxine (43%)
• haloperidol
• MAO inhibitors: contraindicated; may cause hypertension, tachycardia, seizures, death; separate by 2 week washout
• selegiline: in combination increases risk of serotonin syndrome
• clonidine: decreased central hypotensive effects
• potential increased toxicity with:

• tricyclic antidepressants ( TCA), fluoxetine, sertraline, phenothiazines, class 1C antiarrhythmic agents, some beta blockers

• any drug that inhibits cyt P450 2D6 may increase level of venlafaxine
• alcohol can increase adverse effects of venlafaxine [12]
  
• drug interaction(s) of methylene blue with SNRIs
• drug interaction(s) of linezolid with SNRIs
• drug interaction(s) of antidepressants with benzodiazepines

Mechanism-of-action

• inhibits reuptake of serotonin (> norepinephrine [11])
• inhibits reuptake of norepinephrine (< serotonin [11])
• weakly inhibits dopamine reuptake

More General Terms

• serotonin & norepinephrine reuptake inhibitor

Additional Terms

• cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
• desvenlafaxine; norvenlaxafine (Pristiq)

Internet Database

PubChem: 5656
PubChem: 62923

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#: [1] (subscription needed) [2]
8. Prescriber's Letter 9(8):38 2002
9. Prescriber's Letter 10(10):57 2003 Detail-Document#: [3] (subscription needed) [4]
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: [5]
    - 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. <PubMed> PMID: [6] <Internet> [7]
11. Prescriber's Letter 11(9): 2004 Detail-Document#: [8] (subscription needed) [9]
12. FDA Medwatch [10]
13. Prescriber's Letter 16(1): 2009 COMMENTARY: New Venlafaxine Extended-Release Formulation LETTER: New Venlafaxine Extended-Release Formulation Detail-Document#: [11] (subscription needed) [12]
14. Prescriber's Letter 16(2): 2009 Comparison of Venlafaxine and Desvenlafaxine (Pristiq) Detail-Document#: [13] (subscription needed) [14]
15. FDA NEWS RELEASE: June 29, 2010 FDA Approves First Generic Effexor Extended Release Capsules to Treat Major Depressive Disorder [15]
16. Effexor EX Prescribing Information [16]
17. Prescriber's Letter 17(8): 2010 CHART: Comparison of Venlafaxine and Desvenlafaxine CHART: State Regulations on Generic Substitution Detail-Document#: [17] (subscription needed) [18]
18. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010

venlafaxine (Effexor XR)