Serotonin release by platelets plays an important role in hemostasis. SSRIs and SNRIs may increase anticoagulation effect of warfarin. .zanubrutinibMonitor Closely (2)sertraline will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. sertraline, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.ziprasidoneMonitor Closely (1)sertraline and ziprasidone both decrease QTc interval. Modify Therapy/Monitor Closely.zolmitriptanMonitor Closely (1)zolmitriptan and sertraline both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)sertraline, zolmitriptan. Mechanism: unknown. Minor/Significance Unknown. Risk of weakness, dyspnea, chest pain. >10% Nausea (26%) Diarrhea/loose stools (20%) Insomnia (20%) Dry mouth (14%) Fatigue (12%) Dizziness (12%) Somnolence (11%) 1-10% Tremor (9%) Dyspepsia (8%) Ejaculation failure (8%) Agitation (8%) Decreased appetite (7%) Hyperhidrosis (7%) Libido decreased (6-7%) Constipation (6%) Palpitations (4%) Visual impairment (4%) Vomiting (4%) Erectile dysfunction (4%) Ejaculation disorder (3%) Male sexual dysfunction (2%) <2% Cardiac disorders – Tachycardia Ear and labyrinth disorders – Tinnitus Endocrine disorders – Hypothyroidism Eye disorders - Mydriasis, blurred vision Gastrointestinal disorders - Hematochezia, melena, rectal hemorrhage General disorders and administration site conditions - Edema, gait disturbance, irritability, pyrexia Hepatobiliary disorders - Elevated liver enzymes Immune system disorders – Anaphylaxis Metabolism and nutrition disorders - Diabetes mellitus, hypercholesterolemia, hypoglycemia, increased appetite Musculoskeletal and connective tissue disorders - Arthralgia, muscle spasms, tightness, or twitching Nervous system disorders - Ataxia, coma, convulsion, decreased alertness, hypoesthesia, lethargy, psychomotor hyperactivity, syncope Psychiatric disorders - Aggression, bruxism, confusional state, euphoric mood, hallucination Renal and urinary disorders – Hematuria Reproductive system and breast disorders – Galactorrhea, priapism, vaginal hemorrhage Respiratory, thoracic, and mediastinal disorders - Bronchospasm, epistaxis, yawning Skin and subcutaneous tissue disorders – Alopecia, cold sweat; dermatitis; dermatitis bullous; pruritus; purpura; erythematous, follicular, or maculopapular rash; urticaria Vascular disorders - hemorrhage, hypertension, vasodilation Postmarketing Reports Bleeding or clotting disorders - Increased coagulation times (altered platelet function) Cardiac disorders - AV block, bradycardia, atrial arrhythmias, QTc-interval prolongation, ventricular tachycardia (including torsade de pointes) Endocrine disorders - Gynecomastia, hyperprolactinemia, menstrual irregularities, SIADH Eye disorders - Blindness, optic neuritis, cataract Hepatobiliary disorders - Severe liver events (including hepatitis, jaundice, liver failure with some fatal outcomes), pancreatitis Hemic and lymphatic disorders - Agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness Immune system disorders – Angioedema Metabolism and nutrition disorders - Hyponatremia, hyperglycemia Musculoskeletal and connective tissue disorders - Rhabdomyolysis, trismus Nervous system disorders - Serotonin syndrome, extrapyramidal symptoms (including akathisia and dystonia), oculogyric crisis Psychiatric disorders - Psychosis, enuresis, paranoia Renal and urinary disorders - Acute renal failure Respiratory, thoracic, and mediastinal disorders - Pulmonary hypertension, eosinophilic pneumonia Skin and subcutaneous tissue disorders - Photosensitivity skin reaction and other severe cutaneous reactions, which potentially can be fatal, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) Vascular disorders - Cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome), vasculitis Black Box Warnings 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 Contraindications Hypersensitivity Do not use disulfiram concomitantly with oral solution due to alcohol in preparation Concomitant pimozide: Risk of long QT syndrome Coadministration with serotonergic drugs Do not use MAOIs concomitantly or within 14 days before initiating sertraline or within 14 days after discontinuing sertraline Reactions to concomitant administration with MAO inhibitors include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma Starting sertraline in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome If linezolid or IV methylene blue must be administered, discontinue SSRI immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring (5 weeks for fluoxetine), whichever comes first Cautions Clinical worsening and suicide ideation may occur despite medication Use caution in patients with seizure disorders May worsen mania symptoms or precipitate mania in patients with bipolar disorder Increases risk of hyponatremia and impairment of cognitive/motor functions in the elderly Increases risk of bleeding in patients taking anticoagulants/antiplatelets concomitantly Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy Pregnancy: Conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn (see Pregnancy) In neonates exposed to SNRIs/SSRIs late in third trimester: Risk of complications such as feeding difficulties, irritability, and respiratory problems Avoid abrupt withdrawal Bone fractures reported with antidepressant therapy; consider the possibility if patient presents with bone pain, bruising, or point of tenderness Coadministration with other drugs that enhance the effects of serotonergic neurotransmission (eg, tryptophan, fenfluramine, fentanyl, 5-HT agonists, St. John’s Wort) should be undertaken with caution and avoided whenever possible due to the potential for pharmacodynamic interaction (see Contraindications) May cause false-positive urine immunoassay screening tests for benzodiazepines SSRIs and SNRIs are associated with development of SIADH; hyponatremia reported Sexual dysfunction Use may cause symptoms of sexual dysfunction in both male and female patients; inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider Use of SSRIs, may cause symptoms of sexual dysfunction; in male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm Important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder Discuss potential management strategies to support patients in making informed decisions about treatment Pregnancy Overall, available published epidemiologic studies of pregnant women 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 Some studies have reported increases for specific major birth defects; however, these study results are inconclusive There are clinical considerations regarding neonates exposed to SSRIs during the third trimester of pregnancy Pregnancy exposure registry Monitors pregnancy outcomes in women exposed to antidepressants during pregnancy Encourage patients to enroll by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants Lactation Available data from published literature demonstrate low levels of sertraline and its metabolites in human milk There are no data on the effects of sertraline on milk productionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Selective serotonin reuptake inhibitor; little or no affinity for alpha-adrenergic histamine or cholinergic receptor Absorption Bioavailability: Absorption increased by food Peak plasma time: 4.5-8.4 hr Distribution Protein bound: 98% Metabolism Metabolized by hepatic cytochrome P450 enzymes Metabolites: Minimal potency Elimination Half-life: 26 hr Dialyzable: No Excretion: Urine (12-14% unchanged); feces (40-45%) Pharmacogenomics Several SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) are metabolized by CYP2D6 CYP2D6 is involved in the metabolism of approximately 20% of drugs in clinical use and displays large individual-to-individual variability in activity due to genetic polymorphisms More than 80 CYP2D6 variant alleles have been identified; however, 4 of the most prevalent alleles, CYP2D6*3, *4, *5, and *6, account for 93-97% of CYP2D6 poor metabolizers CYP2D6*4, the most common variant (~25% frequency in whites), causes a splicing defect; CYP2D6*3 (2.7% frequency) causes a frameshift mutation; and CYP3D6*5 (2.6%) is an entire deletion of the CYP2D6 gene; individuals homozygous for these alleles have no CYP2D6 activity The impact of CYP2D6 activity is further complicated in some SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) because in addition to being substrates for CYP2D6, they are also known to moderately inhibit CYP2D6 activity Genetic testing laboratories Genotyping tests for CYP2D6 variants are commercially available through the following companies Applied Biosystems (http://www.appliedbiosystems.com/) GenPath Diagnostics (http://www.genpathdiagnostics.com/) Oral Administration Tablets or capsules: May take with or without food Capsules Swallow capsule whole; do not open, crush, or chew Oral solution preparation Must be diluted before administration Measure dose with calibrated dropper supplied; dropper has 25 mg and 50 mg graduation marks only Mix dose with 4 oz of water, ginger ale, lemon/lime soda, lemonade, or orange juice only A slight haze may appear, which is normal Swallow dose immediately after mixing Storage Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) BRAND FORM. UNIT PRICE PILL IMAGE Zoloft oral- 100 mg tabletZoloft oral- 25 mg tabletZoloft oral- 50 mg tabletZoloft oral- 20 mg/mL liquidsertraline oral- 100 mg tabletsertraline oral- 50 mg tabletsertraline oral- 100 mg tabletsertraline oral- 50 mg tabletsertraline oral- 50 mg tabletsertraline oral- 25 mg tabletsertraline oral- 25 mg tabletsertraline oral- 50 mg tabletsertraline oral- 25 mg tabletsertraline oral- 100 mg tabletsertraline oral- 20 mg/mL liquidsertraline oral- 100 mg tabletsertraline oral- 50 mg tabletsertraline oral- 100 mg tabletsertraline oral- 50 mg tabletsertraline oral- 100 mg tabletsertraline oral- 25 mg tabletsertraline oral- 25 mg tabletsertraline oral- 100 mg tabletsertraline oral- 50 mg tabletsertraline oral- 20 mg/mL liquidsertraline oral- 25 mg tabletsertraline oral- 25 mg tabletsertraline oral- 20 mg/mL liquidCopyright © 2010 First DataBank, Inc.Print Patient Educationsertraline oral SERTRALINE - ORAL (SER-truh-leen) COMMON BRAND NAME(S): Zoloft WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed. USES: Sertraline is used to treat depression, panic attacks, obsessive compulsive disorder, post-traumatic stress disorder, social anxiety disorder (social phobia), and a severe form of premenstrual syndrome (premenstrual dysphoric disorder).This medication may improve your mood, sleep, appetite, and energy level and may help restore your interest in daily living. It may decrease fear, anxiety, unwanted thoughts, and the number of panic attacks. It may also reduce the urge to perform repeated tasks (compulsions such as hand-washing, counting, and checking) that interfere with daily living. Sertraline is known as a selective serotonin reuptake inhibitor (SSRI). It works by helping to restore the balance of a certain natural substance (serotonin) in the brain. HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start using sertraline and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually once daily either in the morning or evening. The tablet or liquid form of this medication may be taken with or