Zoloft (sertraline HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Sertraline, a selective serotonin-reuptake inhibitor (SSRI), is an antidepressant agent.
Sertraline is a selective serotonin-reuptake inhibitor (SSRI). Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin. 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, cholinergic, gamma-aminobutyric acid (GABA), dopaminergic, histaminergic, serotonergic (5-HT1A, 5-HT1B, 5-HT2), or benzodiazepine receptors. The chronic administration of sertraline was found in animals to down regulate brain norepinephrine receptors.
Sertraline does not inhibit monoamine oxidase. Although the mechanism of antidepressant action of antidepressant agents may involve inhibition of the reuptake of various neurotransmitters (i.e., serotonin, norepinephrine) at the presynaptic neuronal membrane, it has been suggested that postsynaptic receptor modification is mainly responsible for the antidepressant action observed during long-term administration of antidepressant agents.
Data from in vitro studies suggest that sertraline is more potent than fluvoxamine, fluoxetine, or clomipramine as a serotonin-reuptake inhibitor. Serotonergic mechanisms also appear to be involved at least in part in a number of other pharmacologic effects associated with SSRIs, including sertraline, such as decreased food intake and altered food selection as well as decreased alcohol intake.
Sertraline appears to be slowly but well absorbed from the GI tract following oral administration. The oral bioavailability of sertraline in humans has not been fully elucidated because a preparation for IV administration is not available. However, the relative proportion of an oral dose that reaches systemic circulation unchanged appears to be relatively small because sertraline undergoes extensive first-pass metabolism.
In animals, the oral bioavailability of sertraline ranges from 22 to 36%. The manufacturer states that bioavailability of a single dose of sertraline hydrochloride tablets is approximately equal to that of an equivalent dose of sertraline hydrochloride oral solution.
The effect of food on absorption of sertraline hydrochloride given as tablets or oral solution has been studied in single-dose studies. Administration of a sertraline hydrochloride tablet with food slightly increased the AUC of sertraline, increased peak plasma concentrations by approximately 25%, and decreased the time to achieve peak plasma concentrations from about 8 to 5.5 hours. Administration of sertraline capsules with food causes a small increase in maximum serum concentration and AUC.
Peak plasma sertraline concentrations usually occur within 4.5 to 8.4 hours following oral administration of 50 to 200 mg once daily for 14 days. Peak plasma sertraline concentrations following administration of single oral doses of 50 to 200 mg are proportional and linearly related to dose. Peak plasma concentrations and bioavailability are increased in geriatric individuals.
Following multiple dosing, steady-state plasma sertraline concentrations should be achieved after approximately 1 week of once-daily dosing. When compared with a single dose, there is an approximate 2-fold accumulation of sertraline after multiple daily dosing in dosages ranging from 50 to 200 mg daily. N-Desmethylsertraline, sertraline's principal metabolite, exhibits time-related, dose-dependent increases in AUC (0-24 hour), peak plasma concentrations, and trough plasma concentrations with about a 5- to 9-fold increase in these parameters between days 1 and 14.
Distribution of sertraline and its metabolites into human body tissues and fluids has not been fully characterized. However, limited pharmacokinetic data suggest the drug and some of its metabolites are widely distributed in body tissues. The drug crosses the blood-brain barrier in humans and animals.
At in vitroplasma concentrations ranging from 20 to 500 ng/mL, sertraline is approximately 98% bound to plasma proteins, principally to albumin and alpha1-acid glycoprotein. Protein binding is independent of plasma concentrations from 20 to 2000 mcg/mL. However, sertraline and N-desmethylsertraline did not alter the plasma protein binding of two other highly protein bound drugs, warfarin or propranolol, at concentrations of 300 and 200 ng/mL, respectively.
Like some other SSRIs, sertraline undergoes metabolism via N-demethylation to form N-desmethylsertraline, the principal metabolite. Data from in vivo and in vitrostudies have shown that N-desmethylsertraline is approximately 5 to 10 times less potent as an inhibitor of serotonin reuptake than sertraline; however, the metabolite retains selectivity for serotonin reuptake compared with either norepinephrine or dopamine reuptake.
The elimination half-life of sertraline averages approximately 25 to 26 hours and that of desmethylsertraline averages about 62 to 104 hours. In geriatric adults, elimination half-life may be increased (e.g., to about 36 hours); however, such prolongation does not appear clinically important and does not warrant dosing alterations. Following oral administration, sertraline and its metabolites are excreted in both urine and feces.
Following oral administration of a single, radiolabeled dose in 2 healthy males, unchanged sertraline accounted for less than 5% of plasma radioactivity. Approximately 40 to 45% of the radiolabeled dose was excreted in urine within 9 days. Unchanged sertraline was not detectable in urine.
During the same period, approximately 40 to 45% of the radiolabeled drug was eliminated in feces, including 12 to 14% of unchanged sertraline.
USES: This medication is used to treat certain mental/mood disorders (such as depression, panic attacks, obsessive compulsive disorder, post-traumatic stress disorder, social anxiety disorder). It is also used to treat a severe form of premenstrual syndrome (premenstrual dysphoric disorder). Sertraline belongs to a class of drugs known as selective serotonin reuptake inhibitors (SSRIs).
It works by helping to restore the balance of a certain natural substance (serotonin) in the brain.
Generic name: sertraline HCl
Pronunciation: (SER-truh-leen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Zoloft
Indications
The following indications are listed for Zoloft:
- Major Depressive Disorder
- Obsessive-Compulsive Disorder
- Panic Disorder
- Post Traumatic Stress Disorder
- Premenstrual Dysphoric Disorder
- Social Phobia
Also known as: Major Unipolar Illness, Obsessive Compulsive Neurosis, Panic Reaction, Panic-Like Sensation, Post-Traumatic Stress Syndrome, Posttraumatic Stress Disorder, Social Anxiety Disorder, Unipolar Mood Disorder.
Dosing
Dosage of sertraline hydrochloride is expressed in terms of sertraline. The capsule formulation is only approved for use in the treatment of major depressive disorder in adults and obsessive-compulsive disorder in adults and pediatric patients >=6 years of age.
Sertraline is administered orally as tablets, capsules, or oral solution. The drug usually is administered once daily in the morning or evening, with or without food.
Commercially available sertraline hydrochloride concentrate for oral solution is a clear, colorless solution with a menthol scent containing 20 mg of sertraline per mL and 12% alcohol. When the oral solution is used, measure the dose carefully using the calibrated dropper provided by the manufacturer. The dropper has 25 mg and 50 mg graduation marks only. Dilute the appropriate dose in 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice before administration. Mix the diluted solution and administer immediately. A slight haze may occasionally appear in the diluted oral solution, but the manufacturer states that this is normal. Sertraline hydrochloride oral solution should be diluted only in the liquids specified by the manufacturer, and should be used immediately after dilution.
Swallow sertraline capsules whole; do not open, crush, or chew the capsules.
Store sertraline tablets, capsules, and concentrate for oral solution at 20-25degreesC (excursions permitted between 15-30degreesC).
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Sertraline is a cytochrome P-450 (CYP) 2D6 inhibitor with less inhibitory effects at lower dosages. In vivo and preclinical drug interaction studies demonstrate sertraline does not inhibit CYP3A4 activity; however, it may have some CYP3A4 and hepatic microsomal inducer activity.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Concomitant use with monoamine oxidase inhibitors (MAOIs) or use within 14 days of stopping MAOIs (including linezolid and IV methylene blue) due to an increased risk of serotonin syndrome.
*Concomitant use with pimozide due to the risk of QTc prolongation.
*Known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to sertraline or any of the inactive ingredients of the formulation.
*Sertraline oral solution only: concomitant use with disulfiram.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse reactions in pooled placebo-controlled clinical trials (incidence of >=5% and twice that observed in the placebo group) were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of sertraline in children with obsessive-compulsive disorder (OCD) younger than 6 years of age have not been established. Safety and efficacy of sertraline in pediatric patients with other disorders (e.g., major depressive disorder, panic disorder, posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), social anxiety disorder) have not been established. The overall adverse effect profile of sertraline in 281 pediatric patients who received sertraline in placebo-controlled clinical trials was generally similar to that seen in the adult clinical studies. As with other SSRIs, decreased appetite and weight loss have been observed in association with sertraline therapy.
Monitor all patients being treated with antidepressants for clinical worsening, suicidal thoughts, and unusual changes in behavior, especially during the initial few months of treatment, or at times of dosage increases or decreases. Monitor weight and growth in pediatric patients.
The oral sertraline solution contains 12% alcohol.
Overall, available published epidemiologic studies of pregnant females exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in comparator populations. Studies that have reported specific major birth defects are inconclusive.
Animal studies have not demonstrated teratogenicity; however, delayed fetal ossification was observed when sertraline was administered during the period of organogenesis at doses less than the maximum recommended human dose (MRHD) in rats and doses 3.1 times the MRHD in rabbits on a mg/m2 basis in adolescents. When sertraline was administered to female rats during the last third of gestation, there was an increase in the number of stillborn pups and pup deaths during the first 4 days after birth at the MRHD.
Data from observational studies report exposure to SSRIs, particularly in the month before delivery, is associated with a less than a 2-fold increase in the risk of postpartum hemorrhage. Exposure to SSRIs and SNRIs, including sertraline, in late pregnancy may lead to increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). When treating a pregnant female with sertraline during the third trimester, carefully consider both the potential risks and benefits of treatment. Monitor neonates exposed to sertraline in the third trimester of pregnancy for PPHN and drug discontinuation syndrome.
Females who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than females who continue antidepressants. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.
There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to antidepressants during pregnancy. Advise patients to register by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregi stry/antidepressants/.
Sertraline oral solution contains 12% alcohol and is not recommended during pregnancy because there is no known safe level of alcohol exposure during pregnancy.
Available data demonstrate low sertraline levels in human milk (average of 2% of maternal sertraline serum levels; range of 0-15% of maternal sertraline serum levels) with no adverse reactions observed in infants in a pooled analysis of 53 mother-infant pairs. There are no data on the effects of sertraline on milk production. Consider developmental and health benefits of breastfeeding along with the mother's clinical need for sertraline and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
Dosage selection for elderly patients should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.
The effect of age on the elimination of sertraline has not been fully elucidated. Plasma clearance of sertraline was approximately 40% lower in a group of 16 geriatric patients (8 males and 8 females) who received 100 mg of the drug for 14 days than that reported in a similar study involving younger individuals (from 25-32 years of age). Based on these results, the manufacturers state that steady-state should be achieved in about 2-3 weeks in older individuals. In addition, decreased clearance of the sertraline metabolite, N-desmethylsertraline, was noted in older males but not in older females.
Of the total number of patients in clinical studies of sertraline for major depressive disorder, OCD, panic disorder, PTSD, social anxiety disorder, and PMDD, 797 (17%) were >=65 years of age and 197 (4%) were >=75 years of age.
No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dosage selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
In 354 geriatric patients treated with sertraline for major depressive disorder in placebo-controlled trials, the overall profile of adverse effects was generally similar to younger patients, except for tinnitus and arthralgia with an incidence of at least 2% and at a rate greater than placebo in geriatric patients.
SSRIs, including sertraline, and SNRIs have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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