Sertraline 25 mg · Tablets

Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT).

Absorption — Following oral once-daily sertraline hydrochloride dosing over the range of 50 to 200 mg for 14 days, mean peak plasma concentrations (C max) of sertraline occurred between 4.5 to 8.4 hours post-dosing. The average terminal elimination half-life of plasma sertraline is about 26 hours. Consistent with the terminal elimination half-life, there is an approximately two-fold accumulation up to steady-state concentrations, which are achieved after one week of once-daily dosing. Linear dose-proportional pharmacokinetics were demonstrated in a single dose study in which the C maxand area under the plasma concentration time curve (AUC) of sertraline were proportional to dose over a range of 50 to 200 mg. The single dose bioavailability of sertraline hydrochloride tablets is approximately equal to an equivalent dose of sertraline oral solution. Administration with food causes a small increase in C maxand AUC.

Metabolism — Sertraline undergoes extensive first pass metabolism. The principal initial pathway of metabolism for sertraline is N-demethylation. N-desmethylsertraline has a plasma terminal elimination half-life of 62 to 104 hours. Both in vitrobiochemical and in vivopharmacological testing have shown N-desmethylsertraline to be substantially less active than sertraline. Both sertraline and N-desmethylsertraline undergo oxidative deamination and subsequent reduction, hydroxylation, and glucuronide conjugation. In a study of radiolabeled sertraline involving two healthy male subjects, sertraline accounted for less than 5% of the plasma radioactivity. About 40 to 45% of the administered radioactivity was recovered in urine in 9 days. Unchanged sertraline was not detectable in the urine. For the same period, about 40 to 45% of the administered radioactivity was accounted for in feces, including 12 to 14% unchanged sertraline.

Desmethylsertraline exhibits time-related, dose dependent increases in AUC (0-24-hour), C maxand C min,with about a 5- to 9-fold increase in these pharmacokinetic parameters between day 1 and day 14.

Protein Binding — In vitroprotein binding studies performed with radiolabeled 3H-sertraline showed that sertraline is highly bound to serum proteins (98%) in the range of 20 to 500 ng/mL. However, at up to 300 and 200 ng/mL concentrations, respectively, sertraline and N-desmethylsertraline did not alter the plasma protein binding of two other highly protein bound drugs, warfarin and propranolol.

Pediatric Patients — Sertraline pharmacokinetics were evaluated in a group of 61 pediatric patients (29 aged 6 to12 years, 32 aged 13 to 17 years) including both males (N=28) and females (N=33). Relative to the adults, pediatric patients aged 6 to12 years and 13 to 17 years showed about 22% lower AUC (0 to 24 hr) and C maxvalues when plasma concentration was adjusted for weight. The half-life was similar to that in adults, and no gender-associated differences were observed [See Dosage and Administration (2.1), Use in Specific Populations (8.4)] .

Geriatric Patients — Sertraline plasma clearance in a group of 16 (8 male, 8 female) elderly patients treated with 100 mg/day of sertraline hydrochloride for 14 days was approximately 40% lower than in a similarly studied group of younger (25 to 32 year old) individuals. Steady-state, therefore, was achieved after 2 to 3 weeks in older patients. The same study showed a decreased clearance of desmethylsertraline in older males, but not in older females [See Use in Specific Populations (8.5)] .