Paroxetine

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Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradenames: Paxil (paroxetine hydrochloride), Paxeva (paroxetine mesylate).

Indications

• treatment of depression
• treatment of anxiety [4,12]
• obsessive-compulsive disorder ( OCD)
• self-injurious behavior
• irritable bowel syndrome ( IBS) [11]

Contraindications

• do NOT use with 14 days of MAO inhibitor
• < 18 years of age; risk of suicidal ideation [14]
• no clinical efficacy in children; increased risk of serious adverse effects [16]
  

• pregnancy category = d
• safety in lactation = ?

Dosage

• start 10 mg PO QD
• max 50 mg/day
• do not abruptly discontinue; taper over 2-4 weeks [6,13]

• Tabs: 10, 20, 30, 40 mg.
• Suspension: 10 mg/5 mL.
• Paxil CR*: enteric coated, controlled release, QD dosing
• Tabs: 12.5, 25, 37.5 mg (correspond to 10, 20 & 30 mg of Paxil, respectively) [9]
• * Paxil CR (Galaxo) NOT longer acting, but released lower in the intestine than Paxil. Alledgedly reduces nausea. [15]

Pharmacokinetics

• only 80% of Paxil CR dose absorbed
• extensive cyt P450 metabolism by cyt P450 2D6
• elimination 1/2life: 21 hours
• metabolites excreted in the urine & bile
  

• elimination via liver
• elimination via kidney
• 1/2life = 7-37 hours
• protein binding = 95 %
• elimination by hemodialysis = -

Adverse-effects

• common (> 10%)

• headache, asthenia, nausea*, dry mouth, constipation, diarrhea*, somnolence, dizziness, insomnia, sweating, sexual dysfunction,

• less common (1-10%)

• tremor, anorexia, flatulence, nervousness, anxiety, paresthesias, vomiting, decreased libido, palpitations, vasodilation, postural hypotension

• other

• SIADH & hyponatremia [10]
• greater potential for anti- cholinergic effects than fluoxetine ( Prozac)
• may be symptoms of withdrawal after chronic use or high dose [6]
• may increase risk of suicidal behavior in children & adolescents [13,19]
• SSRI-induced neonatal withdrawal syndrome
• birth defects ?, ventricular septal defect [17,18]
• exposure during the 1st trimester may increase the risk for congenital malformations, particularly cardiac [18]

• * Paxil CR marketed to have fewer GI effects [9]
  

• drug adverse effects of SSRIs
• drug adverse effects of antidepressants

Drug-interactions

• increased effects/toxicity when used concurrently with:

• tryptophan
• alcohol
• cimetidine
• MAO inhibitors (hyperpyrexic crisis)

• trazodone, nefazodone ( serotonin syndrome)
• increased effects/toxicity of:

• sertraline
• phenothiazines
• class 1C antiarrhythmic agents
• warfarin

• decreased effect when used concurrently with:

• phenobarbital
• phenytoin

• paroxetine strongly inhibits cyt P450 2D6, thus increased levels & potentiation of drugs metabolized by cyt P450 2D6

• donepezil
• tricyclic antidepressants
• risperidone ( Risperdal) [7]
• fluoxetine ( Prozac),
• inhibits its own metabolism
  

• drug interaction(s) of anti-platelet agents with SSRIs
• drug interaction(s) of methylene blue with SSRIs
• drug interaction(s) of linezolid with SSRIs
• drug interaction(s) of hypericum perforatum (Sr John's wort) with SSRI
• drug interaction(s) of tamoxifen with SSRI
• drug interaction(s) of antidepressants with benzodiazepines
• drug interaction(s) of NSAIDs with SSRIs
• drug interaction(s) of tamoxifen with paroxetine

Laboratory

• specimen: plasma ( EDTA)
• methods: HPLC

Mechanism-of-action

• selective serotonin re-uptake inhibitor (SSRI)
• less stimulating that fluoxetine ( Prozac)
• more sedating than other SSRIs
• inhibits cyt P450 2D6
• mild muscarinic receptor antagonism (rarely significant)

More General Terms

• selective serotonin reuptake inhibitor (SSRI)

Additional Terms

• cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

Internet Database

PubChem: 43815
PubChem: 4691
PubChem: 5284605
PubChem: 206527
PubChem: 62879

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
3. Prescriber's Letter 7(2):8, Feb. 2000
4. Prescriber's Letter 8(5):28 2001
5. Department of Veterans Affairs, VA National Formulary
6. Prescriber's Letter 8(10):55-56 2001
7. Prescriber's Letter 8(12):67 2001
8. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
9. Prescriber's Letter 9(5):27 2002
10. Prescriber's Letter 9(7):38 2002
11. Prescriber's Letter 9(12):71 2002
12. Journal Watch 23(10):80-81, 2003 Rickels K et al, Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study. J. Psychiatry 160(Apr):749-56, 2003 PMID: [1]
13. Prescriber's Letter 10(7):40 2003
14. Prescriber's Letter 10(10):57 2003 Detail-Document#: [2] (subscription needed) [3]
15. Prescriber's Letter 10(12):68 2003
16. 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: [4]
    - 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: [5] <Internet> [6]
17. Prescriber's Letter 12(9): 2005 Paxil (Paroxetine) and Birth Defects Detail-Document#: [7] (subscription needed) [8]
18. FDA MedWatch [9] [10] [11]
19. FDA MedWatch [12]
20. Prescriber's Letter 13(1): 2006 Detail-Document#: [13] (subscription needed) [14]

paroxetine (Paxil, Pexeva, Seroxat)