FDA Approved
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT). 12.2 Pharmacodynamics Studies at clinically relevant doses have demonstrated that sertraline blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that sertraline is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro studies have shown that sertraline has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. The chronic administration of sertraline was found in animals to down regulate brain norepinephrine receptors. Sertraline does not inhibit monoamine oxidase. Alcohol In healthy subjects, the acute cognitive and psychomotor effects of alcohol were not potentiated by ZOLOFT. Cardiac Electrophysiology The effect of sertraline on the QTc interval was evaluated in a randomized, double-blind, placebo- and positive-controlled three-period crossover thorough QTc study in 54 healthy adult subjects. At 2-fold the maximum recommended daily dose (~3-fold the steady-state exposure for sertraline and N-desmethylsertraline), the largest mean ΔΔQTc was 10 ms with upper bound of two-sided 90% confidence interval of 12 ms. The length of the QTc interval was also positively correlated with serum concentrations of sertraline and N- desmethylsertraline concentrations. These concentration-based analyses, however, indicated a lesser effect on QTc at maximally observed concentration than in the primary analysis [See Warnings and Precautions (5) , Adverse Reactions (6) , Drug Interactions (7) , Overdosage (10) ] . 12.3 Pharmacokinetics Absorption Following oral once-daily ZOLOFT dosing over the range of 50 to 200 mg for 14 days, mean peak plas...
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [See Warnings and Precautions (5.1) ] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients ( 5.1 ) • Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors ( 5.1 )
4 CONTRAINDICATIONS ZOLOFT is contraindicated in patients:
Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [See Warnings and Precautions (5.2) , Drug Interactions (7.1) ] .
Taking pimozide [See Drug Interactions (7.1) ] .
With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [See Adverse Reactions (6.1 , 6.2) ] . In addition to the contraindications for all ZOLOFT formulations listed above, ZOLOFT oral solution is contraindicated in patients:
Taking disulfiram. ZOLOFT oral solution contains alcohol, and concomitant use of ZOLOFT and disulfiram may result in a disulfiram-alcohol reaction.
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