Escitalopram

WARNINGS: SUICIDAL THOUGHTS AND BEHAVIORS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clnical-and-research- programs/pregnancyregistry/antidepressants/

Risk Summary

Available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage. There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and poor neonatal adaptation (see Clinical Considerations) with exposure to selective serotonin reuptake inhibitors (SSRIs), including escitalopram oxalate, during pregnancy. There are risks associated with untreated depression in pregnancy (see Clinical Considerations).

In animal reproduction studies, both escitalopram and racemic citalopram have been shown to have adverse effects on embryo/fetal and postnatal development, including fetal structural abnormalities, when administered at doses greater than human therapeutic doses (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal risk and/or embryo/fetal risk

Women who discontinue antidepressants are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective longitudinal study of 201 pregnant women with a history of major depression, who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.

Fetal/Neonatal adverse reactions

Neonates exposed to SSRIs or SNRIs, including escitalopram oxalate, late in third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5.2)].

Data

Human Data

Exposure to SSRIs, particularly later in pregnancy, may increase the risk for PPHN. PPHN occurs in 1 to 2 per 1000 live births in the general populations and is associated with substantial neonatal morbidity and mortality.

Animal Data

In a rat embryo/fetal development study, oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses [approximately ≥ 55 times the maximum recommended human dose (MRHD) of 20 mg/day on a mg/m 2 basis]. Maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was present at all dose levels. The developmental no- effect dose of 56 mg/kg/day is approximately 27 times the MRHD of 20 mg on a mg/m 2 basis. No malformations were observed at any of the doses tested (as high as 73 times the MRHD on a mg/m 2 basis).

When female rats were treated with escitalopram (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and growth retardation were noted at 48 mg/kg/day which is approximately 23 times the MRHD of 20 mg on a mg/m 2 basis. Slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) was seen at this dose. Slightly increased offspring mortality was also seen at 24 mg/kg/day. The no-effect dose was 12 mg/kg/day which is approximately 6 times the MRHD of 20 mg on a mg/m 2 basis.

In two rat embryo/fetal development studies, oral administration of racemic citalopram (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose, which is approximately 18 times the MRHD of 60 mg/day on a mg/m 2 basis. This dose was also associated with maternal toxicity (clinical signs, decreased body weight gain). The developmental no- effect dose was 56 mg/kg/day is approximately 9 times the MRHD on a mg/m 2 basis. In a rabbit study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day, or approximately 5 times the MRHD on a mg/m 2 basis. Thus, developmental effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit.

When female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were observed at the highest dose, which is approximately 5 times the MRHD of 60 mg on a mg/m 2 basis. The no-effect dose was 12.8 mg/kg/day is approximately 2 times the MRHD on a mg/m 2 basis. Similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, approximately 4 times the MRHD on a mg/m 2 basis. A no-effect dose was not determined in that study.

8.2 Lactation

Risk Summary

Data from the published literature report the presence of escitalopram and desmethylescitalopram in human milk (see Data). There are reports of excessive sedation, restlessness, agitation, poor feeding and poor weight gain in infants exposed to escitalopram, through breast milk (see Clinical Considerations). There are no data on the effects of escitalopram or its metabolites on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for escitalopram oxalate and any potential adverse effects on the breastfed child from escitalopram oxalate or from the underlying maternal condition.

Clinical Considerations

Infants exposed to escitalopram oxalate should be monitored for excess sedation, restlessness, agitation, poor feeding and poor weight gain.

Data

A study of 8 nursing mothers on escitalopram with daily doses of 10 to 20 mg/day showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram.

8.4 Pediatric Use

The safety and effectiveness of escitalopram oxalate have been established in adolescents (12 to 17 years of age) for the treatment of major depressive disorder [see Clinical Studies ( 14.1)]. Although maintenance efficacy in adolescent patients with major depressive disorder has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.

The safety and effectiveness of escitalopram oxalate have not been established in pediatric (younger than 12 years of age) patients with major depressive disorder. In a 24-week, open-label safety study in 118 children (aged 7 to 11 years) who had major depressive disorder, the safety findings were consistent with the known safety and tolerability profile for escitalopram oxalate.

Safety and effectiveness of escitalopram oxalate has not been established in pediatric patients less than 18 years of age with Generalized Anxiety Disorder.

Decreased appetite and weight loss have been observed in association with the use of SSRIs. Consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an SSRI such as escitalopram oxalate.

8.5 Geriatric Use

Approximately 6% of the 1144 patients receiving escitalopram in controlled trials of escitalopram oxalate in major depressive disorder and GAD were 60 years of age or older; elderly patients in these trials received daily doses of escitalopram oxalate between 10 and 20 mg. The number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. Nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram oxalate cannot be ruled out.

SSRIs and SNRIs, including escitalopram oxalate, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see Hyponatremia ( 5.6) ].

In two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared to young subjects and C max was unchanged [ see Clinical Pharmacology ( 12.3) ]. 10 mg/day is the recommended dose for elderly patients [ see Dosage and Administration ( 2.3) ].

Of 4422 patients in clinical studies of racemic citalopram, 1357 were 60 and over, 1034 were 65 and over, and 457 were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out.

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 50090-4915

NDC: 50090-4915-0 90 TABLET, FILM COATED in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behaviors

Advise patients, their families and caregivers to look for the emergence of suicidal ideation and behavior, especially during treatment and when the dose is adjusted up or down, and instruct them to report such symptoms to their healthcare provider [ see Boxed Warning and Warnings and Precautions ( 5.1) ].

Serotonin Syndrome

Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of escitalopram oxalate with 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 (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid) [ see Warnings and Precautions ( 5.2) ].

Activation of Mania or Hypomania

Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [ see Warnings and Precautions ( 5.5) ].

Abnormal Bleeding

Patients should be cautioned about the concomitant use of escitalopram oxalate and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding [ see Warnings and Precautions ( 5.7) ].

Angle Closure Glaucoma

Patients should be advised that taking escitalopram oxalate can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [ see Warnings and Precautions ( 5.9) ].

Sexual Dysfunction

Advise patients that use of escitalopram oxalate 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 [ see Warnings and Precautions ( 5.11) ].

Concomitant Medications

Since escitalopram is the active isomer of racemic citalopram (Celexa), the two agents should not be coadministered. Patients should be advised to inform their physician if they are taking, or plan to take, any prescription or over- the-counter drugs, as there is a potential for interactions.

Continuing the Therapy Prescribed

While patients may notice improvement with escitalopram oxalate therapy in 1 to 4 weeks, they should be advised to continue therapy as directed.

Interference with Psychomotor Performance

Because psychoactive drugs may impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that escitalopram oxalate therapy does not affect their ability to engage in such activities.

Alcohol

Patients should be told that, although escitalopram oxalate has not been shown in experiments with normal subjects to increase the mental and motor skill impairments caused by alcohol, the concomitant use of escitalopram oxalate and alcohol in depressed patients is not advised.

Pregnancy

Advise pregnant women to notify their healthcare providers if they become pregnant or intend to become pregnant during treatment with escitalopram oxalate.

Advise patients that escitalopram oxalate use later in pregnancy may lead to increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension (PPHN) of the newborn [see Use in Specific Populations ( 8.1)].

Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to escitalopram oxalate during pregnancy [see Use in Specific Populations ( 8.1)].

Lactation

Advise breastfeeding women using escitalopram oxalate to monitor infants for excess sedation, restlessness, agitation, poor feeding and poor weight gain and to seek medical care if they notice these signs [see Use in Specific Populations ( 8.2)].

Need for Comprehensive Treatment Program

Escitalopram oxalate is indicated as an integral part of a total treatment program for MDD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all adolescents with this syndrome. Safety and effectiveness of escitalopram oxalate in MDD has not been established in pediatric patients less than 12 years of age. Antidepressants are not intended for use in the adolescent who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe antidepressant medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured For:
Accord Healthcare, Inc.,
1009 Slater Road,
Suite 210-B,
Durham, NC 27703,
USA.

Manufactured By:
Intas Pharmaceuticals Limited,
Ahmedabad -380054, India.

10 0653 5 6013671

Issued November 2021