Product Information
Registration Status: ActiveSIN13315P
APO-SERTRALINE 50MG CAPSULE is approved to be sold in Singapore with effective from 2007-07-16. It is marketed by PHARMAFORTE SINGAPORE PTE LTD, with the registration number of SIN13315P.
This product contains Sertraline 50mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by Apotex Inc. in CANADA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
Sertraline hydrochloride belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake [T28]. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT1A and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and headache (see Toxicity section below for a more detailed listing of side effects). Compared to other agents in this class, sertraline may cause greater diarrheal and male sexual dysfunction effects [A1844]. Sertraline displays a better safety or tolerability profile than other classes of antidepressants [A1846]. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants or monoamine oxidase inhibitors [T28]. Sertraline has shown therapeutic effectiveness as a treatment for major depressive disorder [A1836], obsessive-compulsive disorder (OCD) [A1838], panic disorder, post-traumatic stress disorder (PTSD) [A1841], premenstrual dysphoric disorder (PMDD) [A1842] and social anxiety disorder (social phobia).
Indication
For the management of major depressive disorder (MDD), posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), panic disorder (PD) with or without agoraphobia, premenstrual dysphoric disorder (PMDD), and social anxiety disorder (SAD) [FDA Label]. It may be used for premature ejaculation and vascular headaches as off-label indications.
Mechanism of Action
The exact mechanism of action sertraline is not fully known, but the drug appears to selectively inhibit the reuptake of serotonin at the presynaptic membrane. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission [FDA Label, T28]. It is suggested that these modifications are responsible for the antidepressant action observed during long term administration of antidepressants. It has also been hypothesized that obsessive-compulsive disorder is caused by the dysregulation of serotonin, as it is treated by sertraline, and the drug corrects this imbalance.
Pharmacokinetics
- Absorption
- Following once-daily administration over the range of 50 to 200 mg for 14 days, mean peak plasma concentrations (Cmax) of sertraline occurred between 4.5 to 8.4 hours post-administration [FDA Label]. The steady-state concentrations are reached after 1 week following once-daily administration, and approximately two-fold accumulation up to steady-state concentrations is observed [FDA Label]. The single dose bioavailability of sertraline tablets is approximately equal to an equivalent dose of sertraline oral solution [FDA Label]. The effects of food on the bioavailability of the sertraline tablet and oral concentrate were studied in subjects administered a single dose with and without food. For the tablet, AUC was slightly increased when drug was administered with food but the Cmax was 25% greater, while the time to reach peak plasma concentration (Tmax) decreased from 8 hours post-dosing to 5.5 hours. For the oral concentrate, Tmax was slightly prolonged from 5.9 hours to 7.0 hours with food.
- Distribution
- Metabolism
- Extensively metabolized in the liver. Sertraline metabolism involves N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid. Sertraline undergoes N-demethylation to form N-desmethylsertraline, which retains substantially less pharmacological activity than its parent compound [FDA Label]. This metabolic pathway is primarily catalyzed by cytochrome P450 (CYP) 2B6, with CYP2C19, CYP3A4 and CYP2D6 contributing to a lesser extent. Both sertraline and N-desmethylsertraline undergo oxidative deamination and subsequent reduction, hydroxylation, and glucuronide conjugation [FDA Label]. Deamination occurs via CYP3A4 and CYP2C19. In vitro studies have shown that monoamine oxidase A and B may also catalyze sertraline deamination. Sertraline N-carbamoyl glucuronidation has also been observed in human liver microsomes.
- Elimination
Toxicity
The most common signs and symptoms associated with non-fatal sertraline overdosage were somnolence, vomiting, tachycardia, nausea, dizziness, agitation and tremor. No cases of fatal overdosage with only sertraline have been reported. Other important signs of overdose include bradycardia, bundle branch block, coma, convulsions, delirium, hallucinations, hypertension, hypotension, manic reaction, pancreatitis, QT-interval prolongation, Torsade de Pointes, serotonin syndrome, stupor, and syncope [FDA Label]. Oral LD50 of sertraline in mice and rats are 419 - 548 mg/kg and 1327 - 1591mg/kg, respectively [MSDS]. In a lifetime carcinogenicity studies on mice and rats, there was no significant evidence of sertraline-induced carcinogenic effects despite observable dose-related increases in liver adenomas in male mice receiving sertraline at 10-40 mg/kg and an increase in follicular adenomas of the thyroid in female rats receiving sertraline at 40 mg/kg [FDA Label]. There was an increase in uterine adenocarcinomas in rats receiving sertraline at 10-40 mg/kg, however this effect was not understood to be drug-related [FDA Label]. There were no signs of genotoxicity nor impairment of fertility in bacterial assays and animal studies [FDA Label].
Active Ingredient/Synonyms
(+)-Sertraline | (1S-cis)-1,2,3,4-tetrahydro-4-(3,4-dichlorophenyl)-N-methyl-1-naphthalenamine | (1S,4S)-sertraline | cis-(+)-sertraline | Sertralina | Sertraline | Sertralinum | Sertraline |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.