PAXIL CR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PAXIL CR (PAXIL CR).
Paroxetine is a selective serotonin reuptake inhibitor (SSRI). It potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuronal membrane, resulting in increased serotonin concentrations in the synaptic cleft.
| Metabolism | Extensively metabolized in the liver primarily via cytochrome P450 enzyme CYP2D6. Paroxetine is a potent inhibitor of CYP2D6. Metabolites are less active and are excreted in urine and feces. |
| Excretion | Renal excretion accounts for approximately 64% of the administered dose, with 2% as unchanged parent drug and the remainder as metabolites. Fecal excretion accounts for about 36%, mostly as metabolites. Less than 1% is excreted in bile. |
| Half-life | The terminal elimination half-life of paroxetine (PAXIL CR) is approximately 15-20 hours. This supports once-daily dosing and requires about 5-7 days to reach steady-state concentration. |
| Protein binding | Approximately 93-95% bound to plasma proteins, primarily alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 3-28 L/kg, with an average of about 13 L/kg. This wide distribution indicates extensive tissue partitioning, with brain concentrations several times higher than plasma. |
| Bioavailability | Oral bioavailability of PAXIL CR is about 30% due to first-pass metabolism, but is lower than the immediate-release formulation (50%). Food does not significantly affect bioavailability. |
| Onset of Action | Oral (controlled-release): Therapeutic effects on depressive symptoms may begin within 1-2 weeks, with full antidepressant response typically observed after 4-6 weeks. For anxiety disorders, onset may be similar or slightly faster (1-2 weeks). |
| Duration of Action | Duration of action is approximately 24 hours with once-daily dosing of the controlled-release formulation. Consistent drug levels over 24 hours provide continuous symptomatic control. Dose adjustments should not occur more frequently than at weekly intervals due to the time to reach steady state. |
12.5-37.5 mg orally once daily in the morning; initial dose 12.5 mg/day, titrate by 12.5 mg/day at intervals of at least 1 week to maximum 50 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Creatinine clearance 30-60 mL/min: use lower end of dosing range (12.5 mg/day maximum). Creatinine clearance <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A or B: initial dose 12.5 mg/day, maximum 25 mg/day. Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Initial dose 12.5 mg/day; maximum 25 mg/day. Increased sensitivity to serotonin reuptake inhibition; monitor for hyponatremia and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PAXIL CR (PAXIL CR).
| Breastfeeding | Paroxetine is excreted into breast milk. M/P ratio is approximately 0.39. Milk levels vary; peak concentration occurs 2-4 hours post-dose. Most studies show no adverse effects in breastfed infants, but cases of irritability, poor feeding, and transient serotonin-like symptoms have been reported. Use caution; monitor infant for drowsiness, restlessness, and weight gain. |
| Teratogenic Risk | First trimester: Increased risk of congenital cardiovascular malformations (primarily septal defects) and persistent pulmonary hypertension of the newborn (PPHN). Third trimester: Risk of neonatal adaptation syndrome (irritability, feeding difficulties, respiratory distress) and prolonged QT interval. Late third trimester exposure may cause serotonin syndrome in neonate. |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term trials. Monitor closely for clinical worsening, suicidality, or unusual changes in behavior.
| Serious Effects |
["Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI","Concomitant use with pimozide or thioridazine","Known hypersensitivity to paroxetine or any component of the formulation"]
| Precautions | ["Clinical worsening and suicide risk","Serotonin syndrome","Bleeding abnormalities","Activation of mania/hypomania","Seizures","Angle-closure glaucoma","Hyponatremia","Bone fractures","Discontinuation syndrome (withdrawal reactions)"] |
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| Fetal Monitoring | Maternal: Monitor for bleeding (especially if combined with NSAIDs or anticoagulants), serotonin syndrome, and mood changes. Fetal: Detailed fetal echocardiography at 18-22 weeks for cardiovascular anomalies. Neonatal: Observe for withdrawal symptoms (serotonin discontinuation syndrome) and respiratory adaptation for at least 48 hours post-delivery. |
| Fertility Effects | Paroxetine may reduce sperm quality, motility, and count in men, potentially impairing fertility. In women, SSRIs may alter menstrual cycle and ovulatory function; studies suggest no major impact on female fertility, but caution is advised for couples planning conception. |