ZOLOFT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOLOFT (ZOLOFT).
Selective serotonin reuptake inhibitor (SSRI); potentiates serotonergic activity in the CNS by blocking the reuptake of serotonin at the presynaptic neuronal membrane, resulting in increased serotonin concentrations in the synaptic cleft.
| Metabolism | Hepatic via CYP2C19, CYP2B6, CYP3A4, CYP2C9, and CYP2D6; active metabolite desmethylsertraline (less potent). |
| Excretion | Renal: <0.5% unchanged; extensive hepatic metabolism; metabolites excreted renally and fecally. |
| Half-life | 26 hours (terminal elimination half-life); steady state achieved in ~1 week; metabolite desmethylsertraline half-life 66 hours. |
| Protein binding | 98% bound primarily to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | 20 L/kg; extensive tissue distribution. |
| Bioavailability | Oral: ~44% due to extensive first-pass metabolism; food increases Cmax by 25%. |
| Onset of Action | Oral: 2-4 weeks for clinical antidepressant effect; no immediate onset. |
| Duration of Action | 24 hours with daily dosing; clinical effect persists after discontinuation due to active metabolite. |
| Molecular Weight | 306.23 |
| Action Class | Selective Seretonin Reuptake inhibitors (SSRIs) |
| Brand Substitutes | Zentalin 100mg Tablet, Sartis 100 Tablet, Sertin 100 Tablet, Sertagress 100mg Tablet, Sermind 100 Tablet |
50 mg orally once daily, increased by 50 mg increments at 1-week intervals up to 200 mg/day for depression, OCD, panic disorder, PTSD, PMDD, social anxiety disorder.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Use with caution in severe renal impairment (CrCl <30 mL/min) due to limited data; consider lower doses or extended intervals. |
| Liver impairment | Child-Pugh A: 25 mg once daily. Child-Pugh B: 25 mg once daily or 50 mg every other day. Child-Pugh C: 25 mg every other day. Increase dose slowly with monitoring. |
| Pediatric use | OCD: 6-12 years: 25 mg once daily; 13-17 years: 50 mg once daily. Increase to maximum 200 mg/day in increments of 25 mg/day (6-12 years) or 50 mg/day (13-17 years) at 1-week intervals. Depression (off-label): 25 mg once daily titrated to 50-200 mg/day. |
| Geriatric use | Initiate at 25 mg once daily. Maximum recommended dose 100 mg/day due to increased risk of hyponatremia, QT prolongation, and falls. Monitor renal function, electrolytes, and drug interactions. |
| 1st trimester | Limited human data; may be associated with increased risk of cardiac malformations (septal defects) and persistent pulmonary hypertension of the newborn (PPHN). Use only if potential benefit outweighs risk. |
| 2nd trimester | Generally considered safer than T1, but data are limited. Monitor for preterm labor and low birth weight. |
| 3rd trimester | Use after 20 weeks' gestation associated with increased risk of PPHN. Neonatal withdrawal syndrome (irritability, feeding difficulties, respiratory distress) may occur. Taper if possible before delivery. |
Clinical note
Comprehensive clinical and safety monograph for ZOLOFT (ZOLOFT).
| Placental transfer | Sertraline crosses the placenta, with cord blood concentrations approximately 30% of maternal serum levels. Active transport and binding to fetal plasma proteins may reduce fetal exposure. |
| Breastfeeding | Sertraline is excreted into breast milk in low levels (infant dose approximately 2% of maternal weight-adjusted dose). No known adverse effects in most infants; however, monitor for drowsiness, poor feeding, or irritability. Preferred SSRI during breastfeeding due to relatively low milk/plasma ratio. |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders.
| Serious Effects |
Concurrent use with MAOIs or within 14 days of MAOI therapyConcurrent use with pimozideHypersensitivity to sertraline or any excipients
| Precautions | Serotonin syndrome, bleeding risk (especially with NSAIDs/aspirin), activation of mania/hypomania, seizure threshold lowering, angle-closure glaucoma, hyponatremia, discontinuation syndrome (with abrupt discontinuation), QT prolongation. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase sertraline levels and risk of toxicity. No other significant food interactions. |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | First trimester: Exposure associated with increased risk of congenital cardiac defects (primarily ventricular septal defects) and persistent pulmonary hypertension of the newborn (PPHN). Second/third trimester: Late pregnancy exposure may increase risk of preterm birth, low birth weight, and neonatal adaptation syndrome (jitteriness, respiratory distress, feeding difficulties). |
| Fetal Monitoring | Monitor maternal blood pressure, mental status, and signs of serotonin syndrome (e.g., tachycardia, hyperthermia, clonus). Fetal monitoring: ultrasound for cardiac anatomy if first-trimester exposure; neonatal assessment for adaptation syndrome and PPHN after delivery. |
| Fertility Effects | Sertraline may cause sexual dysfunction (decreased libido, ejaculatory delay) in both sexes, potentially impairing fertility. No direct evidence of ovulatory suppression in women; men may experience reversible sperm abnormalities. |
| Clinical Pearls | For SSRI naive patients, start at 25 mg or 50 mg daily; titrate by 25-50 mg increments at intervals of at least 1 week. Dosing above 200 mg daily is not recommended due to increased side effects. Use with caution in hepatic impairment - reduce dose or increase dosing interval. QT prolongation risk: avoid in patients with congenital long QT syndrome or concurrent QTc-prolonging drugs. Serotonin syndrome risk: do not use with MAOIs or other serotonergic agents. In pregnancy, may be associated with persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome. Discontinuation syndrome: taper gradually over 1-2 weeks to avoid withdrawal symptoms. |
| Patient Advice | Take with or without food, but be consistent to maintain stable blood levels. · Swallow tablets whole; do not crush or chew the film-coated tablets. · Avoid alcohol as it may increase sedation and impair judgment. · Improvement may take 2-4 weeks; monitor for suicidal thoughts early in therapy. · Do not stop suddenly; discuss with your doctor a taper plan to avoid withdrawal. · Report any signs of allergic reaction, bleeding, or serotonin syndrome (e.g., agitation, hallucinations, fever, muscle rigidity). |