ESCITALOPRAM OXALATE - escitalopram oxalate tablet, film coated
Macleods Pharmaceuticals Limited
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Escitalopram Tablets, USP safely and effectively. See full prescribing information for Escitalopram Tablets, USP. Escitalopram Tablets, USP Initial U.S. Approval: 2002 WARNING: Suicidality and Antidepressant Drugs See full prescribing information for complete boxed warning. Increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders. Escitalopram is not approved for use in pediatric patients less than 12 years of age (5.1). INDICATIONS AND USAGEDOSAGE AND ADMINISTRATIONEscitalopram tablets should generally be administered once daily, morning or evening with or without food (2.1, 2.2).
• No additional benefits seen at 20 mg/day dose (2.1). • 10 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment (2.3). • No dosage adjustment for patients with mild or moderate renal impairment. Use caution in patients with severe renal impairment (2.3). • Discontinuing escitalopram tablets: A gradual dose reduction is recommended (2.4). DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS• Clinical Worsening/Suicide Risk: Monitor for clinical worsening, suicidality and unusual change in behavior, especially, during the initial few months of therapy or at times of dose changes (5.1). • Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: Manage with immediate discontinuation and continuing monitoring (5.2). • Discontinuation of Treatment with escitalopram tablets: A gradual reduction in dose rather than abrupt cessation is recommended whenever possible (5.3). • Seizures: Prescribe with care in patients with a history of seizure (5.4). • Activation of Mania/Hypomania: Use cautiously in patients with a history of mania (5.5). • Hyponatremia: Can occur in association with SIADH (5.6). • Abnormal Bleeding: Use caution in concomitant use with NSAIDs, aspirin, warfarin or other drugs that affect coagulation (5.7). • Interference with Cognitive and Motor Performance: Use caution when operating machinery (5.8). • Use in Patients with Concomitant Illness: Use caution in patients with diseases or conditions that produce altered metabolism or hemodynamic responses (5.9). ADVERSE REACTIONSMost commonly observed adverse reactions (incidence ≥ 5% and at least twice the incidence of placebo patients) are: insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue and somnolence, decreased libido, and anorgasmia (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONSUSE IN SPECIFIC POPULATIONSPregnancy: Use only if the potential benefit justifies the potential risk to the fetus (8.1). Nursing Mothers: Caution should be exercised when administered to a nursing woman (8.3) Pediatric Use: Safety and effectiveness of escitalopram oxalate has not been established in pediatric MDD patients less than 12 years of age (8.4). See 17 for PATIENT COUNSELING INFORMATION. Revised: 10/2012 |
Symptoms associated with discontinuation of escitalopram and other SSRIs and SNRIs have been reported [see Warnings and Precautions (5.3)]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
Table 1
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Age Range
| Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated
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| Increases Compared to Placebo |
<18 | 14 additional cases |
18-24 | 5 additional cases |
| Decreases Compared to Placebo |
25-64 | 1 fewer case |
≥ 65 | 6 fewer cases |
Although anticonvulsant effects of racemic citalopram have been observed in animal studies, escitalopram has not been systematically evaluated in patients with a seizure disorder. These patients were excluded from clinical studies during the product's premarketing testing. In clinical trials of escitalopram, cases of convulsion have been reported in association with escitalopram treatment. Like other drugs effective in the treatment of major depressive disorder, escitalopram should be introduced with care in patients with a history of seizure disorder.
In placebo-controlled trials of escitalopram in major depressive disorder, activation of mania/hypomania was reported in one (0.1%) of 715 patients treated with escitalopram and in none of the 592 patients treated with placebo. One additional case of hypomania has been reported in association with escitalopram treatment. Activation of mania/ hypomania has also been reported in a small proportion of patients with major affective disorders treated with racemic citalopram and other marketed drugs effective in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, escitalopram should be used cautiously in patients with a history of mania.
SSRIs and SNRIs, including escitalopram, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to the 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 SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
Patients should be cautioned about the risk of bleeding associated with the concomitant use of escitalopram and NSAIDs, aspirin, or other drugs that affect coagulation.
TABLE 2
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Treatment-Emergent Adverse Reactions observed with a frequency of ≥ 2% and greater than placebo for Major Depressive Disorder
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Adverse Reaction
| Escitalopram
| Placebo
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| (N=715) % | (N=592) % |
Autonomic Nervous System Disorders
| | |
Dry Mouth | 6% | 5% |
Sweating Increased | 5% | 2% |
Central & Peripheral Nervous System Disorders
| | |
Dizziness | 5% | 3% |
Gastrointestinal Disorders
| | |
Nausea | 15% | 7% |
Diarrhea | 8% | 5% |
Constipation | 3% | 1% |
Indigestion | 3% | 1% |
Abdominal Pain | 2% | 1% |
General
| | |
Influenza-like Symptoms | 5% | 4% |
Fatigue | 5% | 2% |
Psychiatric Disorders
| | |
Insomnia | 9% | 4% |
Somnolence | 6% | 2% |
Appetite Decreased | 3% | 1% |
Libido Decreased | 3% | 1% |
Respiratory System Disorders
| | |
Rhinitis | 5% | 4% |
Sinusitis | 3% | 2% |
Urogenital
| | |
Ejaculation Disorder*†
| 9% | <1% |
Impotence†
| 3% | <1% |
Anorgasmia‡
| 2% | <1% |
TABLE 3
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Treatment-Emergent Adverse Reactions observed with a frequency of ≥ 2% and greater than placebo for Generalized Anxiety Disorder
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Adverse Reactions
| Escitalopram
| Placebo
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| (N=429) % | (N=427) % |
Autonomic Nervous System Disorders
| | |
Dry Mouth | 9% | 5% |
Sweating Increased | 4% | 1% |
Central & Peripheral Nervous System Disorders
| | |
Headache | 24% | 17% |
Paresthesia | 2% | 1% |
Gastrointestinal Disorders
| | |
Nausea | 18% | 8% |
Diarrhea | 8% | 6% |
Constipation | 5% | 4% |
Indigestion | 3% | 2% |
Vomiting | 3% | 1% |
Abdominal Pain | 2% | 1% |
Flatulence | 2% | 1% |
Toothache | 2% | 0% |
General
| | |
Fatigue | 8% | 2% |
Influenza-like Symptoms | 5% | 4% |
Musculoskeletal System Disorder
| | |
Neck/Shoulder Pain | 3% | 1% |
Psychiatric Disorders
| | |
Somnolence | 13% | 7% |
Insomnia | 12% | 6% |
Libido Decreased | 7% | 2% |
Dreaming Abnormal | 3% | 2% |
Appetite Decreased | 3% | 1% |
Lethargy | 3% | 1% |
Respiratory System Disorders
| | |
Yawning | 2% | 1% |
Urogenital
| | |
Ejaculation Disorder**
| 14% | 2% |
Anorgasmia†
| 6% | <1% |
Menstrual Disorder | 2% | 1% |
TABLE 4
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Incidence of Common Adverse Reactions in Patients with Major Depressive Disorder
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Adverse Reaction
| Placebo
| 10 mg/day
| 20 mg/day
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| (N=311)
| Escitalopram
| Escitalopram
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| | (N=310)
| (N=125)
|
Insomnia
| 4% | 7% | 14% |
Diarrhea
| 5% | 6% | 14% |
Dry Mouth
| 3% | 4% | 9% |
Somnolence
| 1% | 4% | 9% |
Dizziness
| 2% | 4% | 7% |
Sweating Increased
| <1% | 3% | 8% |
Constipation
| 1% | 3% | 6% |
Fatigue
| 2% | 2% | 6% |
Indigestion
| 1% | 2% | 6% |
TABLE 5
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Incidence of Sexual Side Effects in Placebo-Controlled Clinical Trials
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Adverse Event
| Escitalopram
| Placebo
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| In Males Only |
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| (N = 407) | (N = 383) |
Ejaculation Disorder (primarily ejaculatory delay) | 12% | 1% |
Libido Decreased | 6% | 2% |
Impotence | 2% | <1% |
| In Females Only |
|
| (N = 737) | (N = 636) |
Libido Decreased | 3% | 1% |
Anorgasmia | 3% | <1% |
Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate the risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when escitalopram is initiated or discontinued.
Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when escitalopram and lithium are coadministered.
There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of an SSRI and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised.
Combined administration of racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are coadministered.
In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited in vivo data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.
For more information, call 1-888-943-3210.
Manufactured for:
Macleods Pharma USA, INC,.
Plainsboro, NJ 08536
Manufactured by:
Macleods Pharmaceutical Ltd.
Baddi, Himachal Pradesh, India.
Revised OCTOBER 2012
ESCITALOPRAM OXALATE
escitalopram oxalate tablet, film coated |
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ESCITALOPRAM OXALATE
escitalopram oxalate tablet, film coated |
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ESCITALOPRAM OXALATE
escitalopram oxalate tablet, film coated |
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Labeler - Macleods Pharmaceuticals Limited (862128535) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
Macleods Pharmaceuticals Limited | 676369519 | ANALYSIS(33342-036, 33342-037, 33342-038), LABEL(33342-036, 33342-037, 33342-038), MANUFACTURE(33342-036, 33342-037, 33342-038), PACK(33342-036, 33342-037, 33342-038) |