Pharm

Paroxetine

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Paroxetine, Paxil, Paroxetine hydrochloride, Pexeva, Paroxetine mesylate, Brisdelle

  • See Also
  1. Selective Serotonin Reuptake Inhibitor (SSRI)
  • Mechanism
  1. Selective Serotonin Reuptake Inhibitor (SSRI)
  • Indications
  1. Major Depression
  2. Obsessive Compulsive Disorder
  3. Suppression of Premature Ejaculation
  4. Generalized Anxiety Disorder or Panic Attacks
  5. Social Anxiety Disorder or Social Phobia
  6. Post-Traumatic Stress Disorder
  7. Premenstrual Dysphoric Disorder
  • Safety
  1. Unknown safety in Lactation (per AAP)
    1. However, undetectable in Breast Milk
    2. Considered ACOG L2 (safer), but often avoided due to Teratogenic effect if patient becomes pregnant
  2. Pregnancy Category D
    1. Anencephaly (Odds Ratio 3.2)
    2. Gastroschisis (Odds Ratio 2.5)
    3. Omphalocele (Odds Ratio 3.5)
    4. Right Ventricular Outflow Obstruction (OR 2.4)
    5. Increased Atrial and Ventricular Septal Defects (Odds Ratio1.8)
      1. Associated with first trimester exposure
      2. (2006) Obstet Gynecol 108:1601-3 [PubMed]
    6. Neonatal antedepressant withdrawal risk
      1. Sanz (2005) Lancet 365:482-7 [PubMed]
  3. References
    1. Reefhuis (2015) BMJ 351: h3190 [PubMed]
  • Background
  1. Generic Drug
  • Preparations
  1. Paxil (Paroxetine hydrochloride)
    1. Generic Paxil is available in United States in 2003
    2. Tablets (lower doses scored): 10, 20, 30, and 40 mg
    3. Oral Suspension: 10 mg/5 ml
  2. Paxil CR Tablets: 12.5, 25, and 37.5 mg
    1. Marketed as reducing GI upset with standard Paxil
    2. Must be swallowed whole without chewing
  3. Brisdelle Capsule (Paroxetine): 7.5 mg
    1. Released in 2013 specifically targeting Hot Flushes
    2. Paroxetine 10 mg generic tablet daily is nearly equivalent (at 6% of the Brisdelle cost)
  4. Pexeva (Paroxetine mesylate)
    1. Likely has similar activity to Paxil but not proven
    2. Was significantly less expensive than original trade name Paxil
  • Dosing
  • Paroxetine HCl Immediate Release
  1. Start
    1. Adults: 20 mg orally at bedtime
    2. Elderly: 10 mg orally at bedtime
  2. Titrate
    1. Adults: Increase by 10 mg every 2 weeks
  3. Maximum: 60 mg daily
    1. Limit max to 40 mg daily in elderly, debilitated or severe liver or kidney Impairment
  • Dosing
  • Other Formulations
  1. Paroxetine Controlled Release (CR)
    1. Start 12.5 mg orally at bedtime
    2. May gradually titrate to 25 to 75 mg at bedtime
  2. Pexeva (Paroxetine mesylate)
    1. Start 20 mg orally at bedtime
    2. Titrate to 20 to 50 mg at bedtime
  • Mechanism
  1. Selective Serotonin Reuptake Inhibitor (SSRI)
  2. Increased Norepinephrine reuptake inhibitor activity
  3. Increased Anticholinergic activity
  • Pharmacokinetics
  1. Half Life: 1 day (shorter than most other SSRIs)
  • Drug Interactions
  1. Metabolized by P450-2D6
  2. Highly Protein bound
    1. Interacts with other Protein bound medications
  3. Strong Cytochrome P450-2D6 Inhibitor
    1. Contraindicated with MAO Inhibitors (including Linezolid)
      1. Allow 2 week wash-out prior to starting MAO Inhibitor
    2. Also contraindicated with Thioridazine, Pimozide, and Tryptophan
    3. Raises Warfarin (Coumadin) levels and associated INR
    4. Raises Tricyclic Antidepressant levels
    5. Cimetidine raises Paroxetine levels
    6. Paroxetine decreases Phenytoin and Digoxin levels
    7. Also Exercise caution with Barbiturates, Theophylline, Risperidone, Atomoxetine
  • Adverse Effects
  1. See Antidepressant Adverse Effects
  2. Increased risk of Gastrointestinal Bleeding
  3. Anticholinergic side effects (Sedation, Constipation)
    1. Avoid in elderly with cognitive disorders
  4. Sedating on the sedation to excitation continuum
    1. Most sedating of the SSRIs (administer at bedtime)
    2. Some patients may have paradoxical activation
  5. Sexual Dysfunction (inhibits nitric oxide synthetase)
    1. See Antidepressant Induced Sexual Dysfunction
    2. More common than with Fluoxetine or Sertraline
  6. Dysesthesia (skin Paresthesias)
  7. Dry Mouth
  8. Constipation
  9. Antidepressant Withdrawal on stopping medication
    1. Reduce dose by 10 mg per day every 5-7 days
    2. Taper down to 5-10 mg before discontinuing
  10. Less anxiety (more Anxiolytic) than other SSRIs
    1. Similar to Serzone on this spectrum
  11. Weight gain
    1. More common than with Fluoxetine or Sertraline
  • Precautions
  1. Use caution in Pediatric Depression
    1. Use may be associated with higher Suicide Risk
  • Resources
  1. Paroxetine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6bb4f0a-1555-4550-a7a4-99609674b1e7
  • References
  1. (2023) Med Lett Drugs Ther 62(1592): 25-32
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 38-9
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia