• Basic Info
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Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability in humans has not been fully elucidated to date, but ranges from 22–36% in animals.

Commercially available tablets and oral concentrate solution are bioequivalent.

Food

Food increases the extent of absorption.

Distribution

Extent

Crosses the blood-brain barrier.

Distributes into breast milk.

Plasma Protein Binding

Approximately 98% bound to plasma proteins, principally to albumin and α₁-acid glycoprotein.

Elimination

Metabolism

Extensively metabolized, probably in the liver to N-desmethylsertraline and several other metabolites. Apparently metabolized by multiple CYP isoenzymes, with none contributing more than 40% to overall metabolism.

N-Desmethylsertraline is approximately 5–10 times less potent an inhibitor of serotonin reuptake than sertraline.

Elimination Route

Excreted in both urine and feces.

Half-life

Averages approximately 25–26 hours for sertraline and 62–104 hours for N-desmethylsertraline.

Special Populations

Because sertraline is extensively metabolized by the liver, hepatic impairment can affect the elimination of the drug.

No clinically important decreases in sertraline clearance observed in patients with renal impairment.

Geriatric patients may have reduced sertraline plasma clearance.

Stability

Storage

Oral

Concentrate Solution or Tablets

25°C (may be exposed to 15–30°C).

Actions

• Mechanism of action as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).
• Has very weak effects on the reuptake of norepinephrine or dopamine and does not exhibit clinically important anticholinergic, antihistaminic, or adrenergic (α₁, α₂, β) blocking activity at usual therapeutic dosages.

Advice to Patients

• Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.
• Although not shown to affect psychomotor performance in healthy individuals, importance of exercising caution while operating hazardous machinery, including automobile driving, until gain experience with the drug’s effects in the individual patient.
• Risks associated with concomitant use with alcohol; concomitant use not recommended.
• Importance of continuing sertraline therapy even if improvement is evident within 1–4 weeks, unless directed otherwise by their clinician.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.
• Importance of informing patients of risk of serotonin syndrome with concurrent use of sertraline and 5-HT₁ receptor agonists (“triptans”) or other serotonergic agents. Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.
• Importance of diluting oral concentrate solution with appropriate liquid just prior to administration.
• Importance of informing patients of other important precautionary information. (See Cautions.)