The most common signs and symptoms associated with non-fatal Sertralina Aserta 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 Sertralina Aserta overdose (single or multiple drugs) include bradycardia, bundle branch block, coma, convulsions, delirium, hallucinations, hypertension, hypotension, manic reaction, pancreatitis, QTc-interval prolongation, Torsade de Pointes, serotonin syndrome, stupor, and syncope.
Overdose ManagementNo specific antidotes for Sertralina Aserta are known. Contact Poison Control (1-800-222-1222) for latest recommendations.
The following adverse reactions are described in more detail in other sections of the prescribing information:
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 Sertralina Aserta (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 Sertralina Aserta 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 Sertralina Aserta-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 Sertralina Aserta (>5% and twice placebo) by indication that were not mentioned previously.
Table 3: Common Adverse Reactions in Pooled Placebo-Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD*
| Sertralina Aserta (N=3066) | Placebo (N=2293) | |
| Cardiac disorders | ||
| Palpitations | 4% | 2% |
| Eye disorders | ||
| Visual impairment | 4% | 2% |
| Gastrointestinal Disorders | ||
| Nausea | 26% | 12% |
| Diarrhea/Loose Stools | 20% | 10% |
| Dry mouth | 14% | 9% |
| Dyspepsia | 8% | 4% |
| Constipation | 6% | 4% |
| Vomiting | 4% | 1% |
| General disorders and administration site conditions | ||
| Fatigue | 12% | 8% |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 7% | 2% |
| Nervous system disorders | ||
| Dizziness | 12% | 8% |
| Somnolence | 11% | 6% |
| Tremor | 9% | 2% |
| Psychiatric Disorders | ||
| Insomnia | 20% | 13% |
| Agitation | 8% | 5% |
| Libido Decreased | 6% | 2% |
| Reproductive system and breast disorders | ||
| Ejaculation failure (1) | 8% | 1% |
| Erectile dysfunction (1) | 4% | 1% |
| Ejaculation disorder (1) | 3% | 0% |
| Male sexual dysfunction (1) | 2% | 0% |
| Skin and subcutaneous tissue disorders | ||
| Hyperhidrosis | 7% | 3% |
| 1 Denominator used was for male patients only (n=1316 Sertralina Aserta; n=973 placebo). * Adverse reactions that occurred greater than 2% in Sertralina Aserta-treated patients and at least 2% greater in Sertralina Aserta-treated patients than placebo-treated patients. | ||
In all placebo-controlled studies in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 368 (12%) of the 3066 patients who received Sertralina Aserta 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 Sertralina Aserta-treated patients:
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 Sertralina Aserta-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.
Table 4: Most Common Sexual Adverse Reactions (≥2% and twice placebo) in Men or Women from Sertralina Aserta Pooled Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD
| Men only | Sertralina Aserta (N=1316) | Placebo (N=973) |
| Ejaculation failure | 8% | 1% |
| Libido decreased | 7% | 2% |
| Erectile dysfunction | 4% | 1% |
| Ejaculation disorder | 3% | 0% |
| Male sexual dysfunction | 2% | 0% |
| Women only | (N=1750) | (N=1320) |
| Libido decreased | 4% | 2% |
In 281 pediatric patients treated with Sertralina Aserta 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 Sertralina AsertaOther infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of < 2% in patients treated with Sertralina Aserta 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
Post-marketing ExperienceThe following adverse reactions have been identified during postapproval use of Sertralina Aserta. 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)
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
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 (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. The chronic administration of sertraline was found in animals to down regulate brain norepinephrine receptors. Sertraline does not inhibit monoamine oxidase.
AlcoholIn healthy subjects, the acute cognitive and psychomotor effects of alcohol were not potentiated by Sertralina Aserta.
Cardiac ElectrophysiologyThe effect of sertraline on the QTc interval was evaluated in a randomized, double-blind, placebo- and positive-controlled three-period crossover thorough QTc study in 54 healthy adult subjects. At 2-fold the maximum recommended daily dose (~3-fold the steady-state exposure for sertraline and N-desmethylsertraline), the largest mean ΔΔQTc was 10 ms with upper bound of two-sided 90% confidence interval of 12 ms. The length of the QTc interval was also positively correlated with serum concentrations of sertraline and N- desmethylsertraline concentrations. These concentration-based analyses, however, indicated a lesser effect on QTc at maximally observed concentration than in the primary analysis.
Following oral once-daily Sertralina Aserta dosing over the range of 50 to 200 mg for 14 days, mean peak plasma concentrations (Cmax) of sertraline occurred between 4.5 to 8.4 hours post-dosing. The average terminal elimination half-life of plasma sertraline is about 26 hours. Consistent with the terminal elimination half-life, there is an approximately two-fold accumulation up to steady-state concentrations, which are achieved after one week of once-daily dosing. Linear dose-proportional pharmacokinetics were demonstrated in a single dose study in which the Cmax and area under the plasma concentration time curve (AUC) of sertraline were proportional to dose over a range of 50 to 200 mg. The single dose bioavailability of Sertralina Aserta tablets is approximately equal to an equivalent dose of Sertralina Aserta oral solution. Administration with food causes a small increase in Cmax and AUC.
MetabolismSertraline undergoes extensive first pass metabolism. The principal initial pathway of metabolism for sertraline is N-demethylation. N-desmethylsertraline has a plasma terminal elimination half-life of 62 to 104 hours. Both in vitro biochemical and in vivo pharmacological testing have shown N-desmethylsertraline to be substantially less active than sertraline. Both sertraline and N-desmethylsertraline undergo oxidative deamination and subsequent reduction, hydroxylation, and glucuronide conjugation. In a study of radiolabeled sertraline involving two healthy male subjects, sertraline accounted for less than 5% of the plasma radioactivity. About 40-45% of the administered radioactivity was recovered in urine in 9 days. Unchanged sertraline was not detectable in the urine. For the same period, about 40-45% of the administered radioactivity was accounted for in feces, including 12-14% unchanged sertraline.
Desmethylsertraline exhibits time-related, dose dependent increases in AUC (0-24-hour), Cmax and Cmin, with about a 5- to 9-fold increase in these pharmacokinetic parameters between day 1 and day 14.
Protein BindingIn vitro protein binding studies performed with radiolabeled 3H-sertraline showed that sertraline is highly bound to serum proteins (98%) in the range of 20 to 500 ng/mL. However, at up to 300 and 200 ng/mL concentrations, respectively, sertraline and N-desmethylsertraline did not alter the plasma protein binding of two other highly protein bound drugs, warfarin and propranolol.
