PAXIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PAXIL (PAXIL).
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the central nervous system by inhibiting the reuptake of serotonin (5-HT) from the synaptic cleft, leading to increased serotonin levels.
| Metabolism | Extensively metabolized primarily via cytochrome P450 (CYP) 2D6, with minor contributions from CYP3A4 and CYP1A2. The parent drug accounts for <1% of excretion. Metabolites include paroxetine catechol and paroxetine glucuronide conjugates. |
| Excretion | Renal: 64% (2% unchanged, 62% as metabolites); Fecal: 36% via bile; urinary excretion of unchanged paroxetine <2%. |
| Half-life | Mean terminal half-life 21 hours (range 3–65 hours); steady-state achieved within 7–14 days; nonlinear kinetics with dose increase leading to disproportionate increases in half-life due to saturable hepatic metabolism (CYP2D6). |
| Protein binding | 93–95% bound to plasma proteins (primarily alpha-1-acid glycoprotein and albumin). |
| Volume of Distribution | 11 L/kg (range 3–28 L/kg); extensive tissue distribution with concentrations in CNS exceeding plasma. |
| Bioavailability | Oral: 50% (range 30–60%; limited by first-pass metabolism); food does not significantly affect extent of absorption, but may slightly delay Tmax. |
| Onset of Action | Oral: 4–6 weeks for full antidepressant effect; partial improvement may be noted in 1–2 weeks; anticholinergic and sedative effects occur within hours. |
| Duration of Action | Designed for once-daily dosing; trough concentrations maintain efficacy over 24 hours; abrupt discontinuation results in withdrawal symptoms within 1–3 days, lasting up to 3 weeks. |
20 mg orally once daily, typically in the morning; may be increased in 10 mg/day increments at intervals of at least 1 week to a maximum of 50 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | For GFR <30 mL/min: initial dose 10 mg/day; maximum 40 mg/day. Hemodialysis: no supplemental dose needed. |
| Liver impairment | Child-Pugh Class A or B: initial dose 10 mg/day; maximum 40 mg/day. Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for patients <18 years; off-label use for OCD in children 7–17 years: starting 10 mg/day, titrate by 10 mg/week to target 20–50 mg/day (max 60 mg/day). |
| Geriatric use | Initial dose 10 mg/day; maximum 40 mg/day. Increase in 10 mg increments at intervals of at least 1 week. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PAXIL (PAXIL).
| Breastfeeding | Paroxetine is excreted into breast milk with an estimated infant dose of ~1% of maternal weight-adjusted dose; M/P ratio is approximately 0.56. Cases of irritability, poor feeding, and drowsiness in breastfed infants have been reported; cautious use recommended, with monitoring for adverse effects. |
| Teratogenic Risk | First trimester: Risk of congenital cardiac defects (primarily ventricular and atrial septal defects) with relative risk ~1.5-1.7; persistent pulmonary hypertension of the newborn (PPHN) risk increased ~2-fold; overall absolute risk <.5% for major malformations. Second/third trimester: Risk of preterm delivery, low birth weight, neonatal serotonin discontinuation syndrome (irritability, feeding difficulties, respiratory distress, tremors). |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Monitor closely for clinical worsening, suicidality, or unusual changes in behavior. Paroxetine is not approved for use in pediatric patients.
| Serious Effects |
["Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI","Concurrent use of pimozide or thioridazine (QT prolongation and pharmacokinetic interaction)","Hypersensitivity to paroxetine or any component of the formulation"]
| Precautions | ["Suicidality risk in children, adolescents, and young adults","Serotonin syndrome (potentially life-threatening) when co-administered with other serotonergic drugs","MAOI interaction (at least 14-day washout period)","Discontinuation syndrome (dizziness, sensory disturbances, anxiety, etc.) upon abrupt withdrawal","Increased risk of bleeding (especially with NSAIDs, aspirin, or anticoagulants)","Activation of mania/hypomania in patients with bipolar disorder","Seizure risk (use caution in patients with seizure disorders)","Angle-closure glaucoma (pupillary dilation risk)","Hyponatremia (elderly, volume-depleted patients)","Bone fracture risk (epidemiological studies)","Fetal harm (epidemiological data suggest increased risk of cardiovascular malformations, particularly ventricular outflow obstructions, with first-trimester exposure; consider risk/benefit)"] |
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| Fetal Monitoring | Maternal: Weight, mood, suicidal ideation, blood pressure, glucose if on concurrent antipsychotics. Fetal/neonatal: Third-trimester ultrasound for growth, amniotic fluid index; neonatal assessment for jitteriness, tachypnea, hypoglycemia, seizures within first 24-48 hours postpartum. |
| Fertility Effects | SSRIs may cause reversible decreased sperm motility and morphology in males; in females, possible anovulatory cycles or alterations in menstrual regularity; no conclusive evidence of impaired fertility in humans, but animal studies show reduced implantation rates. |