|Dosage & Substance||tablet, film coated sertraline hydrochloride|
|Date First Marketed||February 11, 1992|
ZOLOFT is indicated for the treatment of the following:
- Major depressive disorder (MDD)
- Obsessive-compulsive disorder (OCD)
- Panic disorder (PD)
- Posttraumatic stress disorder (PTSD)
- Social anxiety disorder (SAD)
- Premenstrual dysphoric disorder (PMDD)
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.
- Taking pimozide.
- With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema)
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.
The following adverse reactions are described in more detail in other sections of the prescribing information:
- Hypersensitivity reactions to sertraline
- Disulfiram-alcohol reaction when ZOLOFT oral solution is taken with disulfiram
- QT prolongation and ventricular arrhythmias when taken with pimozide
- Suicidal thoughts and behaviors
- Serotonin syndrome
- Increased risk of bleeding
- Activation of mania/hypomania
- Discontinuation syndrome
- Angle-closure glaucoma
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below are from randomized, double-blind, placebo-controlled trials of ZOLOFT (mostly 50 mg to 200 mg per day) in 3066 adults diagnosed with MDD, OCD, PD, PTSD, SAD, and PMDD. These 3066 patients exposed to ZOLOFT for 8 to12 weeks represent 568 patient-years of exposure. The mean age was 40 years; 57% were females and 43% were males.
The most common adverse reactions (≥5% and twice placebo) in all pooled placebo-controlled clinical trials of all ZOLOFT-treated patients with MDD, OCD, PD, PTSD, SAD and PMDD were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 3). The following are the most common adverse reactions in trials of ZOLOFT (≥5% and twice placebo) by indication that were not mentioned previously.
- MDD: somnolence;
- OCD: insomnia, agitation;
- PD: constipation, agitation;
- PTSD: fatigue;
- PMDD: somnolence, dry mouth, dizziness, fatigue, and abdominal pain;
- SAD: insomnia, dizziness, fatigue, dry mouth, malaise.
|General disorders and administration site conditions|
|Metabolism and nutrition disorders|
|Nervous system disorders|
|Reproductive system and breast disorders|
|Ejaculation failure †||8%||1%|
|Erectile dysfunction †||4%||1%|
|Ejaculation disorder †||3%||0%|
|Male sexual dysfunction †||2%||0%|
|Skin and subcutaneous tissue disorders|
Adverse Reactions Leading to Discontinuation in Placebo-Controlled Clinical Trials
In all placebo-controlled studies in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 368 (12%) of the 3066 patients who received ZOLOFT discontinued treatment due to an adverse reaction, compared with 93 (4%) of the 2293 placebo-treated patients. In placebo-controlled studies, the following were the common adverse reactions leading to discontinuation in ZOLOFT-treated patients:
- MDD, OCD, PD, PTSD, SAD and PMDD: nausea (3%), diarrhea (2%), agitation (2%), and insomnia (2%).
- MDD (>2% and twice placebo): decreased appetite, dizziness, fatigue, headache, somnolence, tremor, and vomiting.
- OCD: somnolence.
- PD: nervousness and somnolence.
Male and Female Sexual Dysfunction
Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence.
Table 4 below displays the incidence of sexual adverse reactions reported by at least 2% of ZOLOFT-treated patients and twice placebo from pooled placebo-controlled trials. For men and all indications, the most common adverse reactions (>2% and twice placebo) included: ejaculation failure, decreased libido, erectile dysfunction, ejaculation disorder, and male sexual dysfunction. For women, the most common adverse reaction (≥2% and twice placebo) was decreased libido.
|Male sexual dysfunction||2%||0%|
Adverse Reactions in Pediatric Patients
In 281 pediatric patients treated with ZOLOFT in placebo-controlled studies, the overall profile of adverse reactions was generally similar to that seen in adult studies. Adverse reactions that do not appear in Table 3 (most common adverse reactions in adults) yet were reported in at least 2% of pediatric patients and at a rate of at least twice the placebo rate include fever, hyperkinesia, urinary incontinence, aggression, epistaxis, purpura, arthralgia, decreased weight, muscle twitching, and anxiety.
Other Adverse Reactions Observed During the Premarketing Evaluation of ZOLOFT
Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of < 2% in patients treated with ZOLOFT were:
- – tachycardia
- – tinnitus
- – hypothyroidism
- – mydriasis, blurred vision
- hematochezia, melena, rectal hemorrhage
- – edema, gait disturbance, irritability, pyrexia
- – elevated liver enzymes
- – anaphylaxis
- – diabetes mellitus, hypercholesterolemia, hypoglycemia, increased appetite
- – arthralgia, muscle spasms, tightness, or twitching
- – ataxia, coma, convulsion, decreased alertness, hypoesthesia, lethargy, psychomotor hyperactivity, syncope
- – aggression, bruxism, confusional state, euphoric mood, hallucination
- – hematuria
- – galactorrhea, priapism, vaginal hemorrhage
- – bronchospasm, epistaxis, yawning
- – alopecia; cold sweat; dermatitis; dermatitis bullous; pruritus; purpura; erythematous, follicular, or maculopapular rash; urticaria
- – hemorrhage, hypertension, vasodilation
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of ZOLOFT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- – increased coagulation times (altered platelet function)
- – AV block, bradycardia, atrial arrhythmias, QT-interval prolongation, ventricular tachycardia (including Torsade de Pointes)
- – gynecomastia, hyperprolactinemia, menstrual irregularities, SIADH
- – blindness, optic neuritis, cataract
- – severe liver events (including hepatitis, jaundice, liver failure with some fatal outcomes), pancreatitis
- – agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness
- – angioedema
- – hyponatremia, hyperglycemia
- – trismus
- – serotonin syndrome, extrapyramidal symptoms (including akathisia and dystonia), oculogyric crisis
- – psychosis, enuresis, paroniria
- – acute renal failure
- – pulmonary hypertension
- – photosensitivity skin reaction and other severe cutaneous reactions, which potentially can be fatal, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN)
- cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome), vasculitis
5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients
In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2.
No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.
|Age Range (years)||Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated|
|Increases Compared to Placebo|
|<18||14 additional patients|
|18–24||5 additional patients|
|Decreases Compared to Placebo|
|25–64||1 fewer patient|
|≥65||6 fewer patients|
It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression.
Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing ZOLOFT, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
5.2 Serotonin Syndrome
Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including ZOLOFT, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs. Serotonin syndrome can also occur when these drugs are used alone.
Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
The concomitant use of ZOLOFT with MAOIs is contraindicated. In addition, do not initiate ZOLOFT in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking ZOLOFT, discontinue ZOLOFT before initiating treatment with the MAOI.
Monitor all patients taking ZOLOFT for the emergence of serotonin syndrome. Discontinue treatment with ZOLOFT and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of ZOLOFT with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
5.3 Increased Risk of Bleeding
Drugs that interfere with serotonin reuptake inhibition, including ZOLOFT, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.
Inform patients of the increased risk of bleeding associated with the concomitant use of ZOLOFT and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.
5.4 Activation of Mania or Hypomania
In patients with bipolar disorder, treating a depressive episode with ZOLOFT or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were generally excluded; however, symptoms of mania or hypomania were reported in 0.4% of patients treated with ZOLOFT. Prior to initiating treatment with ZOLOFT, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.
5.5 Discontinuation Syndrome
Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible
ZOLOFT has not been systematically evaluated in patients with seizure disorders. Patients with a history of seizures were excluded from clinical studies. ZOLOFT should be prescribed with caution in patients with a seizure disorder.
5.7 Angle-Closure Glaucoma
The pupillary dilation that occurs following use of many antidepressant drugs including ZOLOFT may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including ZOLOFT, in patients with untreated anatomically narrow angles.
Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including ZOLOFT. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
In patients with symptomatic hyponatremia, discontinue ZOLOFT and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs and SNRIs.
5.9 False-Positive Effects on Screening Tests for Benzodiazepines
False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking ZOLOFT. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of ZOLOFT. Confirmatory tests, such as gas chromatography/mass spectrometry, will help distinguish ZOLOFT from benzodiazepines.
|This Medication Guide has been approved by the U.S. Food and Drug Administration|
|Medication Guide |
Tablets and Oral Solution
|What is the most important information I should know about ZOLOFT? |
ZOLOFT and other antidepressant medicines may cause serious side effects. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if there is an emergency.
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|Do not stop ZOLOFT without first talking to your healthcare provider. Stopping ZOLOFT too quickly may cause serious symptoms including:|
|What is ZOLOFT? |
ZOLOFT is a prescription medicine used to treat:
| || |
|It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider. |
ZOLOFT is safe and effective in treating children with OCD age 6 to 17 years.
It is not known if ZOLOFT is safe and effective for use in children under 6 years of age with OCD or children with other behavior health conditions.
Talk to your healthcare provider if you do not think that your condition is getting better with ZOLOFT treatment.
|Who should not take ZOLOFT? |
Do not take ZOLOFT if you:
|People who take ZOLOFT close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms:|
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|What should I tell my healthcare provider before taking ZOLOFT? |
Before starting ZOLOFT, tell your healthcare provider:
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|Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. |
ZOLOFT and some medicines may interact with each other, may not work as well, or may cause serious side effects.
Your healthcare provider or pharmacist can tell you if it is safe to take ZOLOFT with your other medicines. Do not start or stop any medicine while taking ZOLOFT without talking to your healthcare provider first.
|How should I take ZOLOFT? |
|If you take too much ZOLOFT, call your healthcare provider or poison control center right away, or go to the nearest hospital emergency room right away.|
|What should I avoid while taking ZOLOFT? |
ZOLOFT can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how ZOLOFT affects you. Do not drink alcohol while you take ZOLOFT.
|What are the possible side effects of ZOLOFT? |
ZOLOFT may cause serious side effects, including:
|The most common side effects in adults who take ZOLOFT include:|
| || |
|The most common side effects in children and adolescents who take include abnormal increase in muscle movement or agitation, nose bleeds, urinary incontinence, aggressive reaction, possible slowed growth rate, and weight change. Your child’s height and weight should be monitored during treatment with ZOLOFT. |
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of ZOLOFT. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
|How should I store ZOLOFT? |
|Keep ZOLOFT and all medicines out of the reach of children.|
|General information about the safe and effective use of ZOLOFT |
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ZOLOFT for a condition for which it was not prescribed. Do not give ZOLOFT to other people, even if they have the same condition. It may harm them.
This Medication Guide summarizes the most important information about ZOLOFT. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about ZOLOFT that is written for healthcare professionals.
For more information about ZOLOFT call 1-800-438-1985 or go to www.pfizer.com
|What are the ingredients in ZOLOFT? |
Active ingredient: sertraline hydrochloride
Tablets: dibasic calcium phosphate dihydrate, D&C Yellow #10 aluminum lake (in 25 mg tablet), FD&C Blue #1 aluminum lake (in 25 mg tablet), FD&C Red #40 aluminum lake (in 25 mg tablet), FD&C Blue #2 aluminum lake (in 50 mg tablet), hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, synthetic yellow iron oxide (in 100 mg tablet), and titanium dioxide.
Oral solution: glycerin, alcohol (12%), menthol, butylated hydroxytoluene (BHT)
The most common signs and symptoms associated with non-fatal ZOLOFT overdosage were somnolence, vomiting, tachycardia, nausea, dizziness, agitation and tremor. No cases of fatal overdosage with only sertraline have been reported.
Other important adverse events reported with ZOLOFT overdose (single or multiple drugs) include bradycardia, bundle branch block, coma, convulsions, delirium, hallucinations, hypertension, hypotension, manic reaction, pancreatitis, QT-interval prolongation, Torsade de Pointes, serotonin syndrome, stupor, and syncope.
No specific antidotes for ZOLOFT are known. Contact Poison Control (1-800-222-1222) for latest recommendations.
ZOLOFT contains sertraline hydrochloride, an SSRI. Sertraline hydrochloride has a molecular weight of 342.7 and has the following chemical name: (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride. The empirical formula C17H17NCl2∙HCl is represented by the following structural formula:
Sertraline hydrochloride is a white crystalline powder that is slightly soluble in water and isopropyl alcohol, and sparingly soluble in ethanol.
ZOLOFT tablets for oral administration contain 28.0 mg, 56.0 mg and 111.9 mg sertraline hydrochloride equivalent to 25, 50 and 100 mg of sertraline and the following inactive ingredients: dibasic calcium phosphate dihydrate, D & C Yellow #10 aluminum lake (in 25 mg tablet), FD & C Blue #1 aluminum lake (in 25 mg tablet), FD & C Red #40 aluminum lake (in 25 mg tablet), FD & C Blue #2 aluminum lake (in 50 mg tablet), hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, synthetic yellow iron oxide (in 100 mg tablet), and titanium dioxide.
ZOLOFT oral solution is available in a multidose 60 mL bottle. Each mL of solution contains 22.4 mg sertraline hydrochloride equivalent to 20 mg of sertraline. The solution contains the following inactive ingredients: glycerin, alcohol (12%), menthol, butylated hydroxytoluene (BHT). The oral solution must be diluted prior to administration. The dispenser contains dry natural rubber.