PAXIL
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 329.37 |
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 | Paroxetine is associated with a small increased risk of congenital malformations, particularly cardiovascular defects, when used in the first trimester. Data suggest an approximate 1.5- to 2-fold increased risk of septal heart defects. Risk-benefit assessment is essential; avoid use if possible. |
| 2nd trimester | Use in second trimester is associated with a lower risk of major malformations, but there is a risk of persistent pulmonary hypertension of the newborn (PPHN) and other adverse outcomes. Limited data suggest no major teratogenic risk, but close monitoring is recommended. |
| 3rd trimester | Third-trimester exposure may lead to neonatal withdrawal symptoms or serotonin syndrome in the newborn. Symptoms include irritability, respiratory distress, feeding difficulties, and seizures. Tapering before delivery is considered if clinically feasible. |
Clinical note
Comprehensive clinical and safety monograph for PAXIL (PAXIL).
| Placental transfer | Paroxetine crosses the placenta with a cord-to-maternal plasma ratio of approximately 0.5-0.8, indicating significant placental transfer. |
| Breastfeeding | Paroxetine is excreted into breast milk in low amounts. Relative infant dose is approximately 0.5-3.7% of maternal weight-adjusted dose. Some studies report low serum levels in infants, but adverse effects are rare. However, caution is advised in preterm infants or those with poor drug metabolism. Monitor infant for signs of serotonin excess (e.g., irritability, poor feeding). |
| Lactation Rating | L2 (Possibly Compatible) |
| 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). |
| 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. |
■ 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 with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuationConcurrent use with pimozide or thioridazine due to risk of QT prolongationHypersensitivity to paroxetine or any component of the formulationUse in combination with linezolid or intravenous methylene blue due to serotonin syndrome risk
| 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) |
| Food/Dietary | No significant food interactions; may be taken with or without food. Grapefruit juice does not interact. Avoid excessive alcohol. |
| Clinical Pearls | Paroxetine has a short half-life and is associated with significant withdrawal syndrome upon abrupt discontinuation; taper slowly. It is the most anticholinergic SSRI, causing more constipation, dry mouth, and sedation. Use with caution in elderly due to hyponatremia risk. It is also a weak inhibitor of CYP2D6, potentially increasing levels of co-administered drugs like tamoxifen or metoprolol. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly or change dose without consulting doctor. · May cause drowsiness; avoid driving until you know how you react. · Avoid alcohol while taking this medication. · Notify doctor if you experience serotonin syndrome symptoms: agitation, hallucinations, fast heartbeat, fever, muscle stiffness, nausea, diarrhea. · Inform all healthcare providers you are taking paroxetine, especially before surgery or any new medication. · Do not take with MAOIs or within 14 days of stopping MAOIs. |
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