Citalopram: uses, appearance and warnings

Citalopram capsules are indicated for the treatment of Major Depressive Disorder (MDD) in adults [see Clinical Studies (14) ] . Citalopram capsules is a selective serotonin reuptake inhibitor (SSRI) indicated for treatment of Major Depressive Disorder (MDD) in adults ( 1 ).

30 mg: White to off-white powder filled in size “3” white opaque cap/white opaque body hard gelatin capsules imprinted with “CL” on cap and “30” on body in black ink. Citalopram capsules dosage strength is based on the active moiety, citalopram. Capsules: 30 mg ( 3 )

Citalopram capsules are supplied as: 30 mg capsules: White to off-white powder filled in size “3” white opaque cap/white opaque body hard gelatin capsules imprinted with “CL” on cap and “30” on body in black ink. NDC 59651-964-30 Bottle of 30 capsules Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Citalopram capsules is contraindicated in patients: taking, or within 14 days of stopping, MAOIs (including MAOIs such as linezolid or intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.3) , Drug Interactions (7) ] . taking pimozide because of risk of QT prolongation [see Drug Interactions (7) ] . with known hypersensitivity to citalopram or any of the inactive ingredients in citalopram capsules. Reactions have included angioedema and anaphylaxis [see Adverse Reactions (6.2) ]. Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing an MAOI ( 4 ). Concomitant use of pimozide ( 4 ). Known hypersensitivity to citalopram or any of the inactive ingredients of citalopram capsules ( 4 ).

QT Prolongation and Torsade de Pointes : Dose-dependent QTc prolongation, Torsade de pointes, ventricular tachycardia, and sudden death have occurred. Avoid use of citalopram capsules in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure and patients taking other drugs that prolong the QTc interval. Monitor electrolytes in patients at high risk for hypokalemia or hypomagnesemia. Discontinue citalopram capsules in patients with persistent QTc measurements > 500 ms ( 5.2 , 7 ). Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue citalopram capsules and serotonergic agents and initiate supportive treatment ( 4 , 5.3 , 7 ). Increased Risk of Bleeding : Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.4 ). Activation of Mania or Hypomania : Screen patients for bipolar disorder ( 5.5 ). Discontinuation Syndrome : When discontinuing citalopram capsules, reduce dosage gradually and monitor for discontinuation symptoms. Gradual reduction will require use of another citalopram product ( 5.6 ). Seizures : Use with caution in patients with seizure disorder ( 5.7 ). Angle Closure Glaucoma : Avoid use of citalopram capsules in patients with untreated anatomically narrow angles treated ( 5.8 ). Hyponatremia : Can occur in association with syndrome of inappropriate antidiuretic hormone secretion ( 5.9 ). Sexual Dysfunction : Citalopram capsules may cause symptoms of sexual dysfunction ( 5.10 ). 5.1 Suicidal Thoughts and Behaviors in Adolescent and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. These drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts or Behavior in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric* and Adult Patients Age Range Drug-Placebo Difference in Number of Patients* with Suicidal Thoughts or Behaviors per 1,000 Patients Treated Increases Compared to Placebo <18 years old 14 additional cases 18 to 24 years old 5 additional cases Decreases Compared to Placebo 25 to 64 years old 1 fewer case ≥65 years old 6 fewer cases *Citalopram capsules is not approved for use in pediatric patients. It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults 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 and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication 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 citalopram capsules, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 QT-Prolongation and Torsade de Pointes Citalopram causes dose-dependent QTc prolongation, an ECG abnormality that has been associated with Torsade de Pointes (TdP), ventricular tachycardia, and sudden death, all of which have been observed in postmarketing reports for citalopram [see Adverse Reactions 6.2) ] . Because of the risk of QTc prolongation at higher citalopram doses, it is recommended that citalopram should not be given at doses above 40 mg/day [see Clinical Pharmacology (12.2) ] . Avoid use of citalopram capsules in CYP2C19 poor metabolizers, patients receiving concomitant cimetidine or another CYP2C19 inhibitor, patients with hepatic impairment, and patients who are greater than 60 years of age, because citalopram capsules are only available in a 30 mg dose strength and dosage adjustments are not possible [see Drug Interactions (7) , Use in Specific Populations (8.5 , 8.6 ), Clinical Pharmacology (12.3) ] . Citalopram should be avoided in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure unless the benefits outweigh the risks for a particular patient. Citalopram should also not be used in patients who are taking other drugs that prolong the QTc interval [see Drug Interactions (7) ] . Such drugs include Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone). Electrolyte and/or ECG monitoring is recommended in certain circumstances. …

The following adverse reactions are discussed in greater detail in other sections of the labeling: Hypersensitivity reactions [see Contraindications (4) ] Suicidal Thoughts and Behaviors in Adolescent and Young Adults [see Warnings and Precautions (5.1) ] QT-Prolongation and Torsade de Pointes [see Warnings and Precautions (5.2) ] Serotonin Syndrome [see Warnings and Precautions (5.3) ] Increased Risk of Bleeding [see Warnings and Precautions (5.4) ] Activation of Mania or Hypomania [see Warnings and Precautions (5.5) ] Discontinuation Syndrome [see Warnings and Precautions (5.6) ] Seizures [see Warnings and Precautions (5.7) ] Angle Closure Glaucoma [see Warnings and Precautions (5.8) ] Hyponatremia [see Warnings and Precautions (5.9) ] Sexual Dysfunction [see Warnings and Precautions (5.10) ] Most commonly observed adverse reactions (incidence at least twice the incidence of placebo) a …

Table 5 presents clinically important drug interactions with citalopram capsules. Table 5: Clinically Important Drug Interactions with Citalopram Capsules Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: Concomitant use of SSRIs, including citalopram capsules, and MAOIs increases the risk of serotonin syndrome. Intervention: Citalopram capsules is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.3) , Contraindications (4) , Warnings and Precautions (5.3) ] . Pimozide Clinical Impact: Concomitant use of citalopram with pimozide increases plasma concentrations of pimozide, a drug with a narrow therapeutic index, and may increase the risk of QT prolongation and/or ventricular arrhythmias compared to use of citalopram alone [see Clinical Pharmacology (12.3) ]. …