6 ADVERSE REACTIONS
The following adverse reactions are described in more detail in other sections of the prescribing information:
- Hypersensitivity reactions to sertraline [See Contraindications (4)]
- Disulfiram-alcohol reaction when ZOLOFT oral solution is taken with disulfiram [See Contraindications (4)]
- QTc prolongation and ventricular arrhythmias when taken with pimozide [See Contraindications (4), Clinical Pharmacology (12.2)]
- Suicidal thoughts and behaviors [See Warnings and Precautions (5.1)]
- Serotonin syndrome [See Contraindications (4), Warnings and Precautions (5.2), Drug Interactions (7.1)]
- Increased risk of bleeding [See Warnings and Precautions (5.3)]
- Activation of mania/hypomania [See Warnings and Precautions (5.4)]
- Discontinuation syndrome [See Warnings and Precautions (5.5)]
- Seizures [See Warnings and Precautions (5.6)]
- Angle-closure glaucoma [See Warnings and Precautions (5.7)]
- Hyponatremia [See Warnings and Precautions (5.8)]
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:
- 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
6.2 Post-marketing 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.
- 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) [See Clinical Pharmacology (12.2)]
- 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, paroniria
- Renal and urinary disorders - acute renal failure
- Respiratory, thoracic and mediastinal disorders - pulmonary hypertension
- 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