SERTRALINE HYDROCHLORIDE
Clinical safety rating: caution
MAOIs can cause serotonin syndrome and CYP2D6 inhibitors may increase levels May increase risk of bleeding especially with NSAIDs or warfarin.
Selective serotonin reuptake inhibitor (SSRI); inhibits serotonin reuptake at the presynaptic neuron, enhancing serotonergic neurotransmission
| Metabolism | Primarily hepatic via CYP2B6, CYP2C19, CYP2D6, CYP2C9, and CYP3A4; N-demethylation to norsertraline (active metabolite with reduced potency) |
| Excretion | Approximately 40-45% of the dose is excreted in urine (mostly as metabolites, <2% as unchanged drug) and 40-45% in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 26 hours (range 22-36 hours); achieves steady-state after 5-7 days of once-daily dosing. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 20 L/kg (range 18-25 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% due to extensive absorption and minimal first-pass metabolism (absolute bioavailability ~80-90%, but often cited as ~100% relative to oral solution). |
| Onset of Action | Oral: Initial therapeutic effects on depressive symptoms may appear within 2-4 weeks; full therapeutic benefit typically requires 4-8 weeks. |
| Duration of Action | Duration of action (therapeutic effect) is sustained with once-daily dosing; steady-state concentrations maintained over 24-hour interval. Antidepressant effect persists for weeks after discontinuation due to gradual decline in drug concentration. |
50 mg orally once daily; may increase by 50 mg increments at intervals of at least 1 week up to 200 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), use with caution, consider lower dose or extended interval, but no specific guidelines available. |
| Liver impairment | Child-Pugh Class A: 50 mg once daily. Child-Pugh Class B: 25 mg once daily or 50 mg every other day. Child-Pugh Class C: Not recommended. |
| Pediatric use | Children (6-12 years): 25 mg orally once daily; may increase by 25 mg increments every 1-2 weeks up to 200 mg/day. Adolescents (13-17 years): 50 mg orally once daily; may increase by 50 mg increments every 1-2 weeks up to 200 mg/day. |
| Geriatric use | Initiate at 25 mg once daily; increase by 25 mg increments every 1-2 weeks up to a maximum of 200 mg/day. Lower doses may be effective; monitor for hyponatremia and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome and CYP2D6 inhibitors may increase levels May increase risk of bleeding especially with NSAIDs or warfarin.
| FDA category | Animal |
| Breastfeeding | Sertraline exhibits low transfer into breast milk with an estimated infant dose of 0.5-2.2% of maternal weight-adjusted dose; M/P ratio is approximately 0.5-0.7. Maximum concentration in milk occurs 5-9 hours post-dose. Breastfeeding is generally considered compatible, particularly if the infant is monitored for signs of sedation, irritability, and poor feeding. Cases of adverse effects in infants are rare. |
| 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 pimozide, known hypersensitivity to sertraline, use with MAOIs within 14 days
| Precautions | Serotonin syndrome, discontinuation syndrome, activation of mania/hypomania, increased risk of bleeding, hyponatremia, angle-closure glaucoma, QT prolongation (high doses), use in hepatic/renal impairment |
Loading safety data…
| First trimester: Inconsistent evidence for major congenital malformations; retrospective cohort data suggest small increased risk of cardiovascular malformations (RR 1.36, 95% CI 1.08-1.71). Second/third trimesters: Exposure associated with increased risk of persistent pulmonary hypertension of the newborn (PPHN, OR 1.5-2.0), premature birth, low birth weight, and neonatal adaptation syndrome (including respiratory distress, feeding difficulties, jitteriness, hypoglycemia). |
| Fetal Monitoring | Maternal: Routine depression monitoring, assess bleeding risk (serotonin reuptake inhibition may increase risk of postpartum hemorrhage). Fetal/neonatal: Surveillance for intrauterine growth restriction (IUGR), preterm birth, and neonatal adaptation syndrome (including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, hyperreflexia, tremors). Consider fetal echocardiogram in first-trimester exposure. Postnatal infant monitoring for 48-72 hours. |
| Fertility Effects | Data are limited; sertraline may cause reversible reductions in sperm concentration and motility in males based on animal and some human studies. In females, SSRIs may affect menstrual cycle regularity and ovulatory function. Hyperprolactinemia has been reported rarely. Overall, clinically significant impact on fertility is considered low. |