Sertraline

306.23

306.23

616-708-3

QUC7NX6WMB

DTXSID6023577

N06AB06|N - Nervous system

12

5.1

Solid

1.3±0.1 g/cm3

188-190 °C(lit.)

416.3±45.0 °C at 760 mmHg

205.6±28.7 °C

1.621

H2O: 3.5mg/L

9.16None

9.16

167.3 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated]

MW: 342.70. Crystals, mp 243-245 °C. Specific optical rotation at 23 °C = +37.9 deg (c = 2 in methanol). Solubility at room temperature (mg/ml): water 3.8; 0.1N HCl 0.51; 0.1N NaOH 0.002; ethanol 15.7; isopropyl alcohol 4.3; chloroform 110; acetone 1.1; N,N-dimethylformamide 88; dimethylsulfoxide 147; ethyl acetate 0.20; acetonitrile 0.85; methanolic 0.1N HCl 47; chloroform/methanol (1:1) 134. pKa (ethanol:water, 1:1 v/v): 8.5. density = 1.37 /Sertraline hydrochloride/

3

36/37/38

26-36

Xi

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, P391, and P501|Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The LD50 of sertraline is >2000 mg/kg in rats according to the FDA label. One other references indicates an oral LD50 of in mice and rats of 419 - 548 mg/kg and 1327 - 1591mg/kg, respectively.[MSDS] The most common signs and symptoms associated with a non-fatal sertraline overdose are somnolence, vomiting, tachycardia, nausea, dizziness, agitation, and tremor. No cases of fatal overdose with only sertraline have been reported. Most fatal cases are associated with the ingestion of sertraline with other drugs. Consequences of a sertraline overdose may include serotonin syndrome, hypertension, hypotension, syncope, stupor, coma, bradycardia, bundle branch block, QT-prolongation, torsade de pointes, delirium, hallucinations, and pancreatitis.|IDENTIFICATION: Sertraline is a selective serotonin reuptake inhibitor antidepressant agent. Sertraline hydrochloride is a white solid crystal or powder. It is soluble in water and slightly soluble in isopropyl alcohol. Indications: Psychoanaleptic Antidepressant and bicyclic antidepressant Accepted: Major mental depression and prevention of relapse and recurrence of depression. HUMAN EXPOSURE: Main risks and target organs: Sertraline is a selective serotonin reuptake inhibitor (SSRI). When taken alone it is safer in overdose than most other classes of antidepressants. Patients who ingest a sertraline overdose generally experience only mild neurological and gastroenterological symptoms; significant cardiovascular toxicity is unusual. The serotonergic effects of sertraline may be enhanced when sertraline is combined with tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), carbamazepine, lithium or serotonergic substances. A life threatening serotonin syndrome consisting of hyperthermia, tremor and convulsions can develop when sertraline is ingested with these drugs. Summary of clinical effects: Lightheadedness, drowsiness, tremor in upper extremities; nausea, vomiting, diarrhea. Diagnosis: Diagnosis of sertraline poisoning is clinical and based on history of overdose and/or access to sertraline and the presence of minor neurological and/or gastroenterological symptoms. Co-ingestion of tricyclic antidepressants and/or MAOIs should be suspected and the diagnosis of the serotonin syndrome should be considered in the presence of three or more of the following symptoms: behavioral change (confusion or hypomania), agitation, myoclonus, ocular clonus, sustained ankle clonus, hyperreflexia, sweating, shivering, tremor, diarrhea, motor incoordination, muscle rigidity, fever. The differential diagnoses include neuroleptic malignant syndrome, acute poisoning with strychnine, acute sepsis, or severe metabolic disturbance. Contraindications: Absolute: Hypersensitivity to sertraline. Children less than 15 years old. Co-administration of sumatriptan, non selective monoamine oxidase inhibitor (MAOI) and MAOI B-selective antidepressants. Relative: Co-administration of MAOI A-selective antidepressants. Pregnancy and breast feeding. Routes of exposure: Oral: Sertraline is available as capsules, thus ingestion is the most common route of exposure. Kinetics: Absorption by route of exposure: Sertraline is slowly and completely absorbed from the gastrointestinal tract. Peak plasma concentrations (Cmax) occur between 4.5 and 8.5 hours after ingestion of a single dose. The presence of food slightly increases sertraline bioavailability and Cmax increases by 25%. Sertraline undergoes extensive first pass metabolism in the liver. Distribution by route of exposure: Widely distributed throughout body tissues and highly bound to plasma proteins (about 98 %). The apparent volume of distribution is 20 L/kg. The plasma sertraline level was reported to be 20 to 48 ug/L after at least 1 week of treatment with 100 mg sertraline daily, and it ranged from 40 to 187 ug/L after 200 mg. Plasma sertraline concentrations increase proportionally to the administered dose, unlike fluoxetine and paroxetine. Cmax and area under the plasma concentration-time curve values are increased, and elimination half-life is prolonged in elderly patients but these changes do not appear to warrant dose adjustment in this patient group. Biological half-life by route of exposure: After oral doses, plasma half-life is 24 to 26 hours. Metabolism: Sertraline is extensively metabolized in the liver to N-desmethylsertraline, whose half-life is 2 to 3 times longer than sertraline. N-desmethylsertraline is 10 times less active as an inhibitor of serotonin re-uptake in vitro, and has almost no activity in animal models. Elimination and excretion: N-desmethylsertraline is oxidatively deaminated to desmethylsertraline ketone which, in turn, undergoes hydroxylation to an alpha-hydroxyketone and alcohol; these metabolites are then conjugated and excreted in equal amounts in the urine and feces; a small amount of unchanged drug (less than 0.2 %) is excreted in the urine. There are few data about the excretion of sertraline and its metabolites in breast milk did not detect sertraline in the serum of an infant exclusively breastfed by his mother, after 3 weeks and 7 weeks of treatment, although sertraline could be detected in breast milk. Pharmacology and toxicology: Mode of action: Toxicodynamics: Sertraline is a potent inhibitor of serotonin re-uptake by central nervous system neurones and may interact with other drugs or circumstances which cause serotonin release. The enhancement of the serotonergic effects may produce a life-threatening serotonin syndrome. Sertraline, like the other SSRIs fluoxetine and paroxetine, can inhibit in vivo and in vitro, the hepatic isoenzyme 2D6 of the cytochrome P450 system (CYP2D6), which is involved in the oxidative metabolism of numerous drugs. Caution should be used when combining sertraline with CYP2D6 substrates (desipramine, nortriptyline, haloperidol, thioridazine, flecainide, codeine, propranolol, metoprolol), as sertraline can cause a significant increase in the serum concentrations of these drugs. In vitro studies suggest that sertraline may be a substrate for, but does not inhibit another hepatic iso-enzyme of the cytochrome P450 system, CYP3A3/4, which is involved in the metabolism of carbamazepine. A study performed in healthy volunteers showed no evidence of a pharmacodynamic drug-drug interaction between sertraline and carbamazepine. Pharmacodynamics: Sertraline specifically inhibits central nervous system neuronal re-uptake of serotonin, thus increasing the concentration of the serotonin at the synapse and enhancing of serotonergic neuronal transmission. The increased availability of serotonin is thought to be linked with the improvement in depression accounted for by sertraline treatment. Sertraline has no direct effect on the re-uptake of noradrenaline, dopamine or GABA. Unlike most tricyclic antidepressants, it has no significant affinity for alpha1-adrenergic, H1-histamine, and muscarinic receptors. Furthermore, sertraline does not show significant affinity for D1 and D2 dopaminergic, alpha2 and � adrenergic, benzodiazepine and opioid receptors. The selectivity of sertraline may account for the lower incidence of some adverse effects such as sedation, orthostatic hypotension and anticholinergic effects. Like tricyclic antidepressants, MAOIs, and other SSRIs, sertraline significantly reduces REM (rapid eye movement) sleep density, REM time and the REM percentage of total sleep time in patients with major depression. Adults: Overdoses up to 4500 mg of sertraline alone produced mild drowsiness and serious toxicity did not develop in the 48 patients. Children: In a case series of pediatric overdoses, sertraline caused no symptoms in 10 children less than 5 year old; eight of these received gastrointestinal decontamination. Interactions: Coadministration of drugs increasing the level of serotonin: tricyclic antidepressants, other SSRIs, MAOIs, reversible inhibitors of monoamine oxidase (RIMAs), lithium, may cause a serotonin syndrome. At least 2 weeks should elapse after discontinuing a MAOI before starting therapy with sertraline. Sertraline should be stopped at least 1 week before beginning MAOI therapy. Sertraline should not be concomitantly used with sumatriptan, which is a selective agonist at serotonin type 1D receptors, because of possible hypertensive crises and severe coronary vasoconstriction, and advises a washout period of 1 week after cessation of sertraline. A clinical study involving 103 episodes of migraine in patients taking any SSRIs, did not show evidence of significant adverse effects. Cimetidine inhibits the metabolism of sertraline, leading to increased plasma concentrations; close clinical monitoring and/or reduced sertraline doses are recommended. By extrapolation from data available for fluoxetine, drug interactions with oral anticoagulants and carbamazepine might occur, though in vitro and in vivo studies performed with carbamazepine did not show evidence of interactions and though no cases have been reported to date. Treatment with sertraline was associated with worsening and/or recurrence of the lysergide (LSD) flashbacks in two adolescents with a long history of polydrug abuse. They had stopped taking LSD 10 months before sertraline therapy. Main adverse effects: The most common adverse effects reported with therapeutic doses of sertraline are primarily nausea, diarrhea, dyspepsia, dry mouth, insomnia, somnolence, tremor, dizziness, headache and male sexual dysfunction (delayed ejaculation). These adverse effects are reported to occur in 10 to 20 % of patients, and they cause patients to stop therapy in approximately 1 to 4 % of cases. Manic episodes may be provoked in patients with bipolar disorders. If this occurs, sertraline should be discontinued and a sedative antipsychotic drug should be administered. Less common adverse effects include, pruritus, alopecia, and extrapyramidal symptoms. Several cases of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been reported, mainly in elderly patients. Galactorrhea developed in a 40 year old woman receiving sertraline 150 mg/day during 11 week of dosing. Several cases of stuttering have been described. Bruxism causing significant physical consequences was associated with sertraline and other SSRIs in a case series reported. A case of anisocoria was reported. Increase in serum AST and ALT levels has occurred, and returned to normal after treatment was stopped. Sertraline caused prolonged bleeding time in one patient; agranulocytosis was also reported. ANIMAL/PLANT STUDIES: Symptomatology: decreased food intake, hyperactivity, muscular weakness, convulsions. Chronic toxicity: oral doses of serataline for 6 and 12 months; several adverse effects occurred during the first weeks, including hypersalivation, abnormal movements of the head, disorientation, agitation; resulted in convulsions in 2 dogs; all of these effects where temporary and resolved spontaneously despite continuation of sertraline administration. An increase of liver weight associated with a rise in plasma alkaline phosphatase enzymes was noted, due to the properties of enzyme induction of sertraline. Carcinogenicity: Animal studies: In rats a slight increase in the number of follicular and thyroid adenomas was observed in relation with hepatic enzyme induction; these findings cannot be extrapolated to man, because of species differences in the metabolic mechanisms. Teratogenicity: Animal studies: Fertility in rats was not affected. Sertraline did not show embryotoxic or teratogenic properties in rat and rabbit models. However, in the rat, sertraline caused a delay in fetal ossification and a delay in apparition of teeth in the young. A decrease in food intake inducing a delay in growth in the young, proportional to the administered dose, sometimes associated with hyperactivity, was also observed. Mutagenicity: In vitro and in vivo: sertraline did not show mutagenicity for chromosomes and genes.

Liver test abnormalities have been reported to occur in up to 1% of patients on sertraline, but elevations are usually modest and infrequently require dose modification or discontinuation. Rare instances of acute, clinically apparent episodes of liver injury with marked liver enzyme elevations with or without jaundice have been reported in patients on sertraline. The onset of injury is usually within 2 to 24 weeks and the pattern of serum enzyme elevations has varied from hepatocellular to mixed and cholestatic. Autoimmune (autoantibodies) and immunoallergic features (rash, fever, eosinophilia) are uncommon. Acute liver failure due to sertraline has been described but is very rare.

Examples of drug interactions with serotonin-reuptake inhibitors include potentiation of agents metabolized prominently by CYP1A2 (e.g. beta-adrenergic receptor antagonists, caffeine, several antipsychotic agents, & most tricyclic antidepressants); CYP2C9 (carbamazepine); CYP2C19 (barbiturates, imipramine, propranolol, phenyltoin); CYP2D6 (beta-adrenergic receptor antagonists, some antipsychotics, many antidepressants); CYP3A3/4 (benzodiazepines, carbamazepine, many antidepressants, & several antibiotics). /Serotonin-reuptake inhibitors/|Antidepressants potentiate the effects of alcohol & probably other sedatives. The anticholinergic activity of tricyclic antidepressants can add to that of antiparkinsonism agents, antipsychotic drugs of low potency (especially clozapine & thioridazine), or other compounds with antimuscarinic activity to produce toxic effects. Tricyclic antidepressants have prominent & potentially dangerous interactions with biogenic amines, such as norepinephrine, which normally are removed from their site of action by neuronal uptake. However, drugs that inhibit norepinephrine transport also block the effects of indirectly acting amines, such as tyramine, which must be taken up by sympathetic neurons to release norepinephrine. Presumable by a similar mechanism, tricyclic antidepressants prevent the antihypertensive action of adrenergic neuron blocking agents such as guanadrel. Tricyclic agents & trazodone also can block the centrally mediated antihypertensive action of clonidine. /Antidepressants/|Serotonin-reuptake inhibitors & virtually any agent with serotonin-potentiating activity can interact dangerously or even fatally with MAO inhibitors (particularly long-acting MAO inhibitors). ... The resulting reactions have been referred to as "serotonin syndrome". This syndrome typically includes akasthisia-like restlessness, muscle twitches & myoclonus, hyperreflexia, sweating, penile erection, shivering, & tremor as a prelude to more severe intoxication, with seizures & coma. The reaction is often self-limiting if the diagnosis is made quickly & the offending agents are discontinued. The precise pathophysiological mechanisms underlying these toxic syndromes remain ill-defined. Newer MAO inhibitors (e.g. selegiline, moclobemide) also should be considered to have some risk of such interactions. /Serotonin-reuptake inhibitors/|Because of its extensive protein binding. Sertraline may cause a shift in plasma concns of other drugs similarly tightly protein bound (eg, warfarin, propranolol). the risk of using sertraline in combination with other CNS adrenergic drugs has not been systematically evaluated. Sertraline appears to induce hepatic microsomal enzymes. Patients receiving a sertraline reuptake inhibitor drug in combination with a monoamine oxidase inhibitor may develop serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability, & mental changes (extreme agitation, delirium, coma). At least 14 days should be allowed after starting sertraline before starting a MAOI.|For more Interactions (Complete) data for SERTRALINE (7 total), please visit the HSDB record page.

Sertraline is highly bound to serum proteins, at about 98%-99%.

Sertraline is indicated for the management of major depressive disorder (MDD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), panic disorder (PD), premenstrual dysphoric disorder (PMDD), and social anxiety disorder (SAD). Common off-label uses for sertraline include the prevention of post stroke depression, generalized anxiety disorder (GAD), fibromyalgia, premature ejaculation, migraine prophylaxis, diabetic neuropathy, and neurocardiogenic syncope.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) used in the therapy of depression, anxiety disorders and obsessive-compulsive disorder. Sertraline therapy can be associated with transient asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury.

Antidepressant Agents

Antidepressants, especially serotonin-reuptake inhibitors, also are employed in the management of post-traumatic stress disorder, marked by anxiety, startle, painful recollection of the traumatic events, & disturbed sleep. ... The serotonin-reuptake inhibitors are agents of choice in obsessive-compulsive disorder, as well as in possibly related syndromes of impulse dyscontrol or obsessive preoccupations, including compulsive habits, bulimia (but usually not anorexia) nervosa, & body dysmorphic disorder. While their benefits may be limited, serotonin-reuptake inhibitors offer an important advance in the medical treatment of these often chronic & sometimes incapacitating disorders for which no other medical treatment, by itself, has been consistently effective, the effectiveness of pharmacological treatment of these commonly treatment-resistant disorders is greatly enhanced by use of behavioral treatments. In addition to the wide use of modern antidepressants to treat depression commonly associated with general medical illnesses, several psychosomatic disorders may respond at least partly to treatment with antidepressants of the tricyclic, MAO inhibitor, or serotonin-reuptake inhibitor types. These include chronic pain disorders, including adiabetic & other peripheral neuropathic syndromes (for which tertiaryamine tricyclics are probably superior to fluoxetine); fibromyalgia; peptic ulcer & irritable bowel syndrome; chronic fatigue; cataplexy; tics; migraine; & sleep apnea. /Antidepressants; Serotonin-reuptake inhibitors/|Sertraline is indicated for the treatment of major depressive disorder. Treatment of acute depressive episodes typically requires 6 to 12 months of antidepressant therapy. Patients with recurrent or chronic depression may require long-term treatment. Sertraline showed effective maintenance of antidepressant response for up to 52 weeks of treatment in a placebo-controlled trial. /Included in US product labeling/|Sertraline is indicated for the treatment of obsession and compulsions in adults and children 6 years of age and older with obsessive-compulsive disorder. /Included in US product labeling/|Sertraline is indicated for the treatment of panic disorder with or without agoraphobia. /Included in US product labeling/

Side effects of Sertraline include: mild agitation, minimal sedation, moderately severe GI effects, & moderately severe sexual effects. /from table/|Sertraline has been tested in children 6 to 17 years of age and, in effective doses, has not been shown to cause different side effects or problems than it does in adults. However, the effects of long-term use of sertraline on the growth, development, and maturation of children and adolescents are unknown. Because of the anorectic effect of sertraline, body weight and growth should be monitored in children receiving long-term treatment.|No geriatrics-specific problems have been documented in studies done to date that include elderly patients. However, in one study, clearance of sertraline in 16 elderly patients was about 40% lower than clearance in a group of younger subjects, indicating that the steady-state will take 2 to 3 weeks to achieve in elderly patients. A reduced initial dosage is recommended in elderly patients.|In a single-dose study, mean elimination half-life of sertraline was prolonged from 22 hours in healthy subjects to 52 hours in patients with mild, stable cirrhosis; peak concentrations and AUC were increased 1.7 and 4.4 times, respectively, in patients with hepatic impairment; decreased dosage or less frequent dosing is recommended.|For more Drug Warnings (Complete) data for SERTRALINE (15 total), please visit the HSDB record page.

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. Clinical studies have shown that it improves cognition in depressed patients. 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.

Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. (See all compounds classified as Antidepressive Agents.)|Compounds that specifically inhibit the reuptake of serotonin in the brain. (See all compounds classified as Serotonin Uptake Inhibitors.)

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%. The area under the curve in healthy volunteers after a 100mg dose of sertraline was 456 μg × h/mL in one study. **Effects of food on absorption** The effects of food on the bioavailability of the sertraline tablet and oral concentrate were studied in subjects given a single dose with and without food. For the tablet, AUC was slightly increased when sertraline was administered with food, the Cmax was 25% greater, and the time to peak plasma concentration was shortened by about 2.5 hours. For the oral concentrate preparation of sertraline, peak concentration was prolonged by approximately 1 hour with the ingestion of food.|Since 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.|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 (DMS). Studies have also determined sertraline distributes into the brain, plasma, and serum.|In pharmacokinetic studies, the clearance of a 200mg dose of sertraline in studies of both young and elderly patients ranged between 1.09 ± 0.38 L/h/kg - 1.35 ± 0.67 L/h/kg.|GI absorption: >or= 44%; time to reach peak plasma concn: 6-8 hr; oral clearance (single dose): 96 L/hr; protein binding: 99%; urinary excretion (radioactivity): 44% of oral dose; fecal excretion (radioactivity): 44% of oral dose. /from table/|Sertraline is absorbed readily through the GI tract. Its absolute bioavailability has not been determined in humans. It displays first-order kinetics. Max plasma concns following doses of 50 & 200 mg are 22-29 ug/L (ng/ml). These concns are reached in 4.5-8.4 hr. Serum levels at steady state are 10-120 ng/mL of sertraline & its desmethyl metabolites. Plasma protein binding is extensive (approx 98%) to both albumin & alpha1-acid glycoprotein. At concns up to 300 & 200 ug/mL, respectively, sertraline & N-desmethyl-sertraline do not appear to alter the plasma protein binding of two other highly protein-bound drugs, warfarin & propranolol. Distribution following oral admin of sertraline is biphasic with a prolonged absorption phase. The elimination phase begins 12-16 hr following the dose. The volume of distribution has not been determined in humans but is more than 20 L/kg in rats & dogs. Both sertraline & its metabolites exhibit extensive distribution into tissues outside the blood. ... The elimination half-life (beta) of sertraline in humans is 24-25 hr. The clinically active desmethyl metabolite is eliminated more slowly than the parent drug with a half-life of approx 66 hr. Unchanged sertraline is not detected in the urine.|Slow but consistent. Bioavailablity and absorption rate are increased if sertraline is taken with food.|Both sertraline and its metabolites are extensively distributed into tissues. In animal studies, the volume of distribution (volD) exceeded 20 L/kg.

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. 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.|Sertraline undergoes extensive metabolism. The parent drug is N-demethylated, followed by glucuronidation, deamination, or both. Most metabolites in the urine are alpha-hydroxy-ketone glucuronides.|Depression is one of the most common psychiatric disorders. A variety of different chemical structures have been found to have antidepressant activity. The number is constantly growing; however, as yet, no one group has been found to have a clear therapeutic advantage over the others. The major indication for antidepressant drugs is depression, but a number of side effects have been established by clinical experience and controlled trials. It is clear that, to some extent, any drug or chemical substance administered to the mother is able to cross the placenta unless it is destroyed or altered during metabolism. Placental transport of maternal substrates to the fetus and of substances from the fetus to the mother is established at about the fifth week of fetal life. Traditionally, teratogenic effects of antidepressants or other drugs have been noted as anatomic malformation. It is clear that these are dose- and time-related and that the fetus is at great risk during the first 3 months of gestation. However, it is possible for antidepressants to exert their effects on the fetus at other times during pregnancy as well as to infants during lactation. Administration of antidepressants to pregnant women presents a unique problem for the physician. Not only must maternal pharmacologic mechanisms be taken into consideration when prescribing an antidepressant drug, but the fetus must also be regarded as a potential recipient of the drug. Certain results are evident with regard to drugs administered during lactation. It is essential that physicians need to be aware of the results of animal studies in this area and of the potential risk of maternal drug ingestion to the suckling infant.|Sertraline has known human metabolites that include N-desmethylsertraline.

The elimination half-life of sertraline is approximately 26 hours. One reference mentions an elimination half-life ranging from 22-36 hours.|Elimination half-life, parent (metabolite): 24 (65) hours. /from table/|Elimination half-life: 24 to 26 hours

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. In animal studies, chronic administration of sertraline results in down-regulation of brain norepinephrine receptors. Sertraline displays affinity for sigma-1 and 2 receptor binding sites, but binds with stronger affinity to sigma-1 binding sites. In vitro, sertraline shows little to no affinity for GABA, dopaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. It exerts weak inhibitory actions on the neuronal uptake of norepinephrine and dopamine and exhibits no inhibitory effects on the monoamine oxidase enzyme.|Sertraline is a selective 5-HT reuptake inhibitor. It does not have cardiovascular, anticholinergic, antidopaminergic, convulsant, or monoamine oxidase-inhibiting effects. Most antidepressants are associated with either norepinephrine reuptake inhibition, 5-HT reuptake inhibition, & monoamine oxidase inhibition. Sertraline does not cause significant reuptake blockade of dopamine or norepinephrine. Sertraline through inhibition of 5-HT release, may cause beta-adrenoceptor downregulation.

Treatment of overdose is largely symptomatic & supportive. Patients should be hospitalized where adequate oxygen, cardiac monitoring, & a central line are available. An airway should be established & maintained, & adequate oxygenation & ventilation ensured. Cardiac function & vital signs must be monitored. The possibility of multiple-drug involvement should be considered. Activated charcoal, used with sorbitol, may be as or more effective than emesis. ... Because of the large volume of distribution & extensive protein binding of sertraline, forced diuresis, dialysis, hemoperfusion, & exchange transfusion are not likely to be of benefit. There is no specific antidote. Patients should remain under observation for at least 48 hr after an overdose (the metabolite has a half-life of several days).|/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

A 23 yr old woman with a past history of depression ingested an overdose of 700-1000 mg; a 28 yr old man took an overdose of 2100 mg. Both received gastric lavage & recovered fully with no sequelae. A 43 yr old woman with a past history of depression took an overdose of 1400 mg together with unsuspected amounts of mefenamic acid, temazepam, & alcohol; the patient was discharged the next day with no sequelae. None of the 4 cases of overdose reported to the manufacturer with a max ingestion of 2.6 g of sertraline (equivalent to 13 times the max daily dose) required intensive monitoring & there were no significant changes in vital signs, cardiovascular function, or level of consciousness. ... Up to 4500 mg my be tolerated without profound toxicity.|In a U.S. series of 6 cases of overdose, all experienced lethargy & 4 had sinus tachycardia. All recovered within 24 hr of gastric lavage, activated charcoal, & supportive care. The quantity of sertraline ingested & the time before symptoms were noted were not provided in the report. Sertraline does produce the classic toxic syndrome associated with cyclic antidepressants.|Sertraline has a wide margin of safety in overdose. However, deaths have occurred in overdoses involving sertraline in combination with other drugs and/or alcohol. Symptoms of overdose resemble the side/adverse effects occurring with therapeutic doses, but may be more intense or several symptoms may occur together. The following effects have been selected on the basis of their potential clinical significance ... not necessary inclusive: Anxiety; drowsiness; electrocardiogram (ECG) changes; mydriasis (unusually large pupils); nausea; tachycardia (unusually fast heartbeat); vomiting. NOTE: Some patients may develop the serotonin syndrome, a potentially fatal symptom complex, in response to acute overdose with sertraline. The serotonin syndrome may be manifested by mental status changes, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination, and/or fever.|Limited data are available regarding the use of sertraline (Zoloft) during pregnancy. The California Teratogen Information Service prospectively ascertained 112 pregnant women taking sertraline and compared outcomes to those of 191 women ascertained for nonteratogenic exposures. The rate of major anomalies did not differ significantly between the groups (3.8% vs. 1.9%). Anomalies in the sertraline group included bilateral choanal atresia, valvular pulmonic stenosis with an atrial septal aneurysm, unilateral clubfoot, and Down Syndrome in a pregnancy that was terminated. Among the 158 infants who received a dysmorphological examination, the frequency of minor anomalies was similar in the two groups. There was a nonsignificant excess of spontaneous abortions in the sertraline group (16.7% vs. 10.9%, p = 0.17). Infants exposed to sertraline in the third trimester compared to those with earlier exposure or controls were more often premature (16.3%, 9.3%, 7.5%, trend p = 0.10), had neonatal transition difficulty (adj OR 10.3, 95% CI 3.9, 27.1), or were admitted to a special care nursery (adj OR 6.9, 95% CI 2.5, 25.9). Furthermore, there was evidence of a dose response relationship for the latter two endpoints. These data confirm previous findings indicating that sertraline is not a structural teratogen. They provide further evidence that neonatal complications are more common in infants born to women who take SSRI's late in pregnancy.|For more Human Toxicity Excerpts (Complete) data for SERTRALINE (6 total), please visit the HSDB record page.

Altruline

Active ingredient in the drug Zoloft produced by Pfizer (oral concentrate and oral tablets) /Sertraline hydrochloride/

A rapid and sensitive determination of sertraline in human plasma using gas chromatography-mass spectrometry.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals