PAROXETINE HYDROCHLORIDE
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.
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by blocking the reuptake of serotonin into presynaptic neurons, increasing serotonin availability in the synaptic cleft.
| Metabolism | Extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP2D6, with minor contributions from CYP3A4 and CYP1A2. The major metabolites are paroxetine catechol glucuronide and paroxetine sulfate conjugate, which are inactive. |
| Excretion | Renal (64% as metabolites, 2% unchanged); biliary/fecal (36%) |
| Half-life | 20-24 hours (mean 21 h); requires 5-7 days to steady state; increased in hepatic/renal impairment |
| Protein binding | 95% bound to albumin and alpha-1 acid glycoprotein |
| Volume of Distribution | 3-28 L/kg (mean 10-20 L/kg); extensive tissue distribution (brain, lungs, liver) |
| Bioavailability | Oral: 50-100% (mean 64%); food does not affect significantly |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; immediate for panic/anxiety (1-2 weeks) |
| Duration of Action | 24 hours (once-daily dosing); sustained by active metabolites (negligible); withdrawal symptoms if abruptly stopped due to receptor adaptation |
20 mg orally once daily, increased if necessary by 10 mg per day at intervals of at least 1 week to a maximum of 50 mg per day.
| Dosage form | TABLET |
| Renal impairment | Creatinine clearance (CrCl) 30-60 mL/min: maximum 40 mg/day; CrCl <30 mL/min: maximum 30 mg/day. |
| Liver impairment | Child-Pugh Class A and B: lower initial dose (10 mg/day) and titrate slowly; maximum 30 mg/day. Child-Pugh Class C: contraindicated. |
| Pediatric use | Major depressive disorder: 10 mg orally once daily, titrate to target 20 mg/day; maximum 50 mg/day. Obsessive-compulsive disorder: Starting 10 mg once daily, target 20-30 mg/day; maximum 60 mg/day. Not approved for children under 7. |
| Geriatric use | Initial dose 10 mg orally once daily; maximum 40 mg/day. Increase in 10 mg increments at intervals of at least 1 week, not to exceed 40 mg/day. |
| 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 with a mean milk-to-plasma (M/P) ratio of 0.89. Relative infant dose is approximately 1-2% of maternal weight-adjusted dose. Cases of drowsiness, irritability, and poor feeding have been reported. Avoid breastfeeding if infant is preterm or has metabolic disorders. |
| Teratogenic Risk |
■ FDA Black Box Warning
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders. Paroxetine is not approved for use in pediatric patients except for obsessive-compulsive disorder.
| Common Effects | anxiety disorders |
| Serious Effects |
["Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation","Concomitant use with thioridazine or pimozide","Known hypersensitivity to paroxetine or any component of the formulation","Use in combination with linezolid or intravenous methylene blue (risk of serotonin syndrome)","Use in pregnancy, especially third trimester, due to risk of persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome","Use in pediatric patients except for obsessive-compulsive disorder (due to increased risk of suicidal ideation and behavior)"]
| Precautions | ["Suicidal thoughts and behaviors in children, adolescents, and young adults","Serotonin syndrome or neuroleptic malignant syndrome-like reactions","Risk of bleeding (e.g., gastrointestinal or cutaneous) especially with NSAIDs or anticoagulants","Activation of mania/hypomania in patients with bipolar disorder","Seizure risk in patients with seizure disorders","Angle-closure glaucoma risk","Sexual dysfunction (e.g., ejaculation disorder, decreased libido)","Hyponatremia (especially in elderly or volume-depleted patients)","Bone fracture risk with long-term use","Discontinuation syndrome upon abrupt withdrawal"] |
Loading safety data…
| First trimester: Increased risk of cardiovascular malformations, particularly ventricular septal defects (RR 1.5-2.0). Second/third trimester: Risk of persistent pulmonary hypertension of the newborn (PPHN) (OR 2.5). Late third trimester: Risk of neonatal adaptation syndrome including respiratory distress, feeding difficulties, irritability, and serotonin syndrome-like symptoms. |
| Fetal Monitoring | Maternal: Monitor for serotonin syndrome, especially with concurrent serotonergic drugs. Assess mood and suicidal ideation. Fetal: Fetal echocardiography recommended at 18-22 weeks if exposed in first trimester. Neonatal observation for adaptation syndrome for 48-72 hours after delivery. |
| Fertility Effects | Paroxetine is associated with increased risk of sexual dysfunction (ejaculatory delay, anorgasmia) which may affect fertility. Reversible upon discontinuation. No direct evidence of impaired spermatogenesis or oogenesis. |