SERTOR 50

Description

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamic properties:

Mechanism of action

Sertraline selectively inhibits the reuptake of serotonin (5-HT) at the presynaptic neuronal membrane, thereby increasing serotonergic activity. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission. These changes are believed to be responsible for the antidepressant action and beneficial effects in obsessive-compulsive (and other anxiety related disorders). It has been hypothesized that obsessive-compulsive disorder, like depression, is also caused by the disregulation of serotonin.

Pharmacodynamic effects

Sertraline improves or relieves the symptoms of depression, OCD, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder via the inhibition of serotonin reuptake.

It has less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not exert significant anticholinergic, antihistamine, or adrenergic (alpha1, alpha2, beta) blocking activity. The onset of action and beneficial effects are usually noticed after 4-6 weeks, for reasons that are not fully understood and currently under investigation.

Pharmacokinetic properties:

Absorption

Following once-daily administration of 50 to 200 mg for two weeks, the mean peak plasma concentrations (Cmax) of sertraline occurred between 4.5 to 8.4 hours after administration, and measured at 20 to 55 μg/L. Steady-state concentrations are reached after 1 week following once-daily administration, and vary greatly depending on the patient. Bioavailability has been estimated to be above 44%.

Distribution

Sertraline is widely distributed, and its volume of distribution is estimated to be more than 20L/kg. Post-mortem studies in humans have measured liver tissue concentrations of 3.9–20 mg/kg for sertraline and between 1.4 to 11 mg/kg for its active metabolite, N-desmethyl-sertraline.

Metabolism

Sertraline is heavily metabolized in the liver and has one major active metabolite. It undergoes N-demethylation to form N-desmethylsertraline, which is much less potent in its pharmacological activity than sertraline.⁷ In addition to N-demethylation, sertraline metabolism involves N-hydroxylation, oxidative deamination, and finally, glucuronidation. The metabolism of sertraline is mainly catalyzed by CYP3A4 and CYP2B6, with some activity accounted for by CYP2C19 and CYP2D6.

Elimination

Sertraline is extensively metabolized, excretion of unchanged drug in the urine is a minor route of elimination, with 12-14% of unchanged sertraline excreted in the feces.

THERAPEUTIC CLASS: Anti- depressant

 

CLINICAL PARTICULARS:

Therapeutic Indication:

• Major depressive episodes. Prevention of recurrence of major depressive episodes.
• Panic disorder, with or without agoraphobia.
• Obsessive compulsive disorder (OCD) in adults and paediatric patients aged 6-17 years.
• Social anxiety disorder.
• Post-traumatic stress disorder (PTSD)

Posology and method of Administration:

Posology:

Depression and OCD:

Sertraline treatment should be started at a dose of 50 mg/day.

Paediatric population

Age 13-17 years: Initially 50 mg once daily.

Age 6-12 years: Initially 25 mg once daily.

Method of Administration:

Sertraline should be administered once daily, either in the morning or evening.

Sertraline tablet can be administered with or without food.

Missed Dose:

If one dose is missed, this dose should be omitted and the next dose should be taken at the usual time with a meal. Do not take a double dose to make up for a forgotten dose.

 

CONTRAINDICATIONS:

• Taking pimozide, a medication used to treat schizophrenia and Tourette’s syndrome.
• Having a history of seizures, as sertraline may increase the risk of having seizures.
• Having a bleeding disorder or taking blood thinners, as sertraline may thin the blood and increase the risk of bleeding.
• Being pregnant or breastfeeding, as sertraline may harm the unborn baby or pass into breast milk.

 

SIDE EFFECTS:

Upper respiratory tract infection, pharyngitis, rhinitis, thrombocytopenia, leukopenia, hypersensitivity, seasonal allergy, hypothyroidism

 

SPECIAL WARNINGS AND PRECAUTIONS FOR USE:

• The risk of Serotonin Syndrome or Neuroleptic Malignant Syndrome with SSRIs is increased with concomitant use of other serotonergic drugs (including other serotonergic antidepressants, amphetamines, triptans), with drugs which impair metabolism of serotonin (including MAOIs e.g. methylene blue), antipsychotics and other dopamine antagonists, and with opiate drugs (e.g. buprenorphine).
• Co-administration of sertraline with other drugs which enhance the effects of serotonergic neurotransmission such as amphetamines, tryptophan or fenfluramine or 5-HT agonists, or the herbal medicine, St John’s Wort (hypericum perforatum), should be undertaken with caution and avoided whenever possible due to the potential for a pharmacodynamic interaction.
• Sertraline should not be used in the treatment of children and adolescents under the age of 18 years, except for patients with obsessive compulsive disorder aged 6-17 years old.

 

OTHER MEDICINES AND SERTRALINE HYDROCHLORIDE TABLETS:

The effect of the following drugs can be influenced (interactions):

• Sertraline must not be used in combination with irreversible MAOIs such as selegiline. Sertraline must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI. Sertraline must be discontinued for at least 7 days before starting treatment with an irreversible MAOI.
• Due to the risk of serotonin syndrome, the combination of sertraline with a reversible and selective MAOI, such as moclobemide, should not be given.
• The antibiotic linezolid is a weak reversible and non-selective MAOI and should not be given to patients treated with sertraline.

 

PREGNANCY AND BREAST-FEEDING

• Being pregnant or breastfeeding, as sertraline may harm the unborn baby or pass into breast milk.

 

DRIVING AND USING MACHINES

Sertraline has no effect on psychomotor performance. However, as psychotropic drugs may impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, the patient should be cautioned accordingly.

 

OVER DOSE:

Somnolence, gastrointestinal disturbances (e.g. nausea and vomiting), tachycardia, tremor, agitation and dizziness.

 

STORAGE:

Store in a cool dry place away from direct sunlight. Keep out of reach of children