PAROXETINE MESYLATE
Clinical safety rating: caution
MAOIs can cause serotonin syndrome and strong inhibitors of CYP2D6 may increase levels May increase risk of bleeding especially with NSAIDs or warfarin.
Selective serotonin reuptake inhibitor (SSRI); potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin from the synaptic cleft.
| Metabolism | Primarily metabolized by CYP2D6; involves CYP3A4 and CYP1A2 to a lesser extent. |
| Excretion | Primarily hepatic metabolism via CYP2D6, with approximately 64% of the dose excreted in urine (2% unchanged paroxetine, 62% as metabolites) and 36% in feces (via bile). |
| Half-life | Terminal elimination half-life is approximately 21 hours (range 17–28 hours) in healthy adults; may be prolonged to 30–35 hours in elderly or hepatic impairment. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 3.1 L/kg (range 2.5–4.5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral: 50% (range 30–60%) due to first-pass metabolism; no intravenous formulation available. |
| Onset of Action | Oral: 4–6 weeks for full antidepressant effect; some improvement may be seen within 1–2 weeks. |
| Duration of Action | 24 hours following oral administration; steady-state achieved within 7–14 days. Clinical effects persist for weeks after discontinuation due to slow elimination. |
10-50 mg orally once daily, usually in the morning; starting dose 20 mg/day, increase by 10 mg/day at weekly intervals. Maximum 50 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-59 mL/min: reduce dose to lower end of range (max 40 mg/day). GFR <30 mL/min: reduce dose further, max 30 mg/day. Not recommended in dialysis. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: starting dose 10 mg/day, max 30 mg/day. Child-Pugh C: contraindicated or use with extreme caution. |
| Pediatric use | Not approved for pediatric depression. For pediatric OCD (age 8-17): starting 10 mg/day, increase by 10 mg increments weekly to max 50 mg/day. Weight-based: 0.2 mg/kg/day initial, max 1.0 mg/kg/day. |
| Geriatric use | Starting dose 10 mg/day orally, increase by 10 mg/day at weekly intervals, max 40 mg/day. Lower initial dose due to reduced clearance and increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome and strong inhibitors of CYP2D6 may increase levels May increase risk of bleeding especially with NSAIDs or warfarin.
| FDA category | Animal |
| Breastfeeding | Paroxetine is excreted into breast milk. Infant serum levels are approximately 1-2% of maternal weight-adjusted dose; M/P ratio is approximately 0.89. Cases of somnolence, decreased feeding, and weight loss have been reported. Benefits of breastfeeding should be weighed against potential risks. |
| Teratogenic Risk |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Common Effects | anxiety disorders |
| Serious Effects |
["Concomitant use with MAOIs or within 14 days of MAOI therapy","Concomitant use with pimozide","Concomitant use with thioridazine","Hypersensitivity to paroxetine or any component of the formulation","Pregnancy (especially third trimester, due to risks of persistent pulmonary hypertension and neonatal adaptation syndrome)"]
| Precautions | ["Suicidality risk in young adults","Serotonin syndrome","QT prolongation","Bone fractures","Hypersensitivity reactions","Angle-closure glaucoma","Seizure threshold lowering","Hyponatremia","Abnormal bleeding risk","Sexual dysfunction","Discontinuation syndrome with abrupt stop"] |
Loading safety data…
| Paroxetine mesylate is classified as Pregnancy Category D. First trimester exposure increases risk of cardiovascular malformations, particularly ventricular septal defects. Second and third trimester exposure may cause persistent pulmonary hypertension of the newborn, preterm birth, and neonatal adaptation syndrome including respiratory distress, feeding difficulties, and irritability. Use only if clearly needed. |
| Fetal Monitoring | Monitor for signs of neonatal adaptation syndrome after delivery. Perform fetal echocardiography in first trimester exposure. Assess for persistent pulmonary hypertension of the newborn. Monitor maternal mental health and potential for relapse. |
| Fertility Effects | Paroxetine may impair male and female fertility based on animal studies. In humans, paroxetine is associated with reduced semen quality and may affect erectile function. Clinical significance is uncertain. |