Citalopram Hydrobromide
Tablet · Oral
Uses
Citalopram is indicated for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies ( 14 )] . Citalopram is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD) in adults ( 1 ).
Dosage and administration
Administer once daily with or without food (2). Initial dosage is 20 mg once daily; after one week may increase to maximum dosage of 40 mg once daily (2.1). Patients greater than 60 years of age, patients with hepatic impairment, and CYP2C19 poor metabolizers: maximum recommended dosage is 20 mg once daily (2.2). When discontinuing Citalopram, reduce dosage gradually (2.4, 5.6 ). 2.1 Recommended Dosage Administer Citalopram once daily, with or without food, at an initial dosage of 20 mg once daily, with an increase to a maximum dosage of 40 mg once daily at an interval of no less than one week. Dosages above 40 mg once daily are not recommended due to the risk of QT prolongation [see Warnings and Precautions ( 5.2 )] . 2.2 Screen for Bipolar Disorder Prior to Starting Citalopram Prior to initiating treatment with Citalopram or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [See Warnings and Precautions ( 5.5 )] . 2.3 Recommended Dosage for Specific Populations The maximum recommended dosage of Citalopram for patients who are greater than 60 years of age, patients with hepatic impairment, and for CYP2C19 poor metabolizers is 20 mg once daily [see Warnings and Precautions ( 5.2 ), Clinical Pharmacology ( 12.3 )] . 2.4 Dosage Modifications with Concomitant Use of CYP2C19 Inhibitors The maxium recommended dosage of Citalopram when used concomitantly with a CYP2C19 inhibitor is 20 mg once daily [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7 ) ]. 2.5 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of therapy with Citalopram. Conversely, at least 14 days must elapse after stopping Citalopram before starting an MAOI antidepressant [see Contraindications ( 4 ) and Warnings and Precautions ( 5.3 )]. 2.6 Discontinuing Treatment with Citalopram Adverse reactions may occur upon discontinuation of Citalopram [see Warnings and Precautions ( 5.6 )]. Gradually reduce the dosage rather than stopping Citalopram abruptly whenever possible.
Dosage forms and strengths
Citalopram tablets, USP are available as: 10 mg: Beige film coated, round, biconvex tablets de-bossed with "IG" on one side and "206" on the other. 20 mg: Pink film coated, round, biconvex tablets de-bossed with "I" on the left side of bisect and "G" on the right side of bisect on one side and "207" on the other. 40 mg: White film coated, round, bi-convex tablets de-bossed with "I" on the left side of bisect and "G" on the right side of bisect on one side and "208" on the other. Tablets: 10 mg; 20 mg, scored; and 40 mg, scored ( 3 )
Contraindications
Citalopram 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. 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 a MAOI. ( 4 ). Concomitant use of pimozide. ( 4 ). Known hypersensitivity to citalopram or any of the inactive ingredients of Citalopram ( 4 ).
Warnings and precautions
5 WARNINGS AND PRECAUTIONS QT-Prolongation and Torsade de Pointes: Dose-dependent QTc prolongation, Torsade de pointes, ventricular tachycardia, and sudden death have occurred. Avoid use of Citalopram 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 in patients with persistent QTc measurements > 500 ms (5.2, 7 ). Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone. If occurs, discontinue Citalopram and initiate supportive measures ( 5.3 ). 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/Hypomania: Screen patients for bipolar disorder ( 5.5 ). Seizures: Use with caution in patients with seizure disorder ( 5.7). Angle-Closure Glaucoma: Avoid use of Citalopram in patients with untreated anatomically narrow angles ( 5.8 ). Hyponatremia: Can occur in association with syndrome of inappropriate antidiuretic hormone secretion ( 5.9 ). Sexual Dysfunction: Citalopram may cause symptoms of sexual dysfunction. ( 5.10 ). 5.1 Suicidal Thoughts and Behavior in Adolescents 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 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. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1 . Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Citalopram is not approved for use in pediatric patients. Drug-Placebo Difference in Number of Patients with Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18-24 years old 5 additional patients Decreases Compared to Placebo 25-64 years old 1 fewer patient ≥65 years old 6 fewer 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 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, 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 post marketing reports for citalopram [see Adverse Reactions 6.2 )] . Because of the risk of QTc prolongation at higher Citalopram doses, it is recommended that Citalopram not be given at doses above 40 mg once daily [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.2 )] . 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 be avoided 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). The citalopram dose should be limited in certain populations. The maximum dose should be limited to 20 mg once daily in patients who are CYP2C19 poor metabolizers or those patients receiving concomitant cimetidine or another CYP2C19 inhibitor, since higher citalopram exposures would be expected. The maximum dose should also be limited to 20 mg once daily in patients with hepatic impairment and in patients who are greater than 60 years of age because of expected higher exposures [see Dosage and Administration ( 2.3 , 2.4 ), Drug Interactions ( 7 ), Use in Specific Populations ( 8.5 ), Clinical Pharmacology ( 12.3 )] . Electrolyte and/or ECG monitoring is recommended in certain circumstances.
Side effects
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 adolescents 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 common adverse reaction (incidence ≥ 5% and twice placebo) is ejaculation disorder (primarily ejaculation delay) ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Exelan Pharmaceuticals Inc. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 studies of another drug and may not reflect the rates observed in clinical practice. The safety for Citalopram included citalopram exposures in patients and/or healthy subjects from 3 different groups of studies: 429 healthy subjects in clinical pharmacology/pharmacokinetic studies; 4,422 exposures from patients in controlled and uncontrolled clinical trials, corresponding to approximately 1,370 patient-exposure years. There were, in addition, over 19,000 exposures from mostly open-label, European postmarketing studies. The conditions and duration of treatment with Citalopram varied greatly and included (in overlapping categories) open-label and double-blind studies, inpatient and outpatient studies, fixed-dose and dose-titration studies, and short-term and long-term exposure. Adverse Reactions Associated with Discontinuation of Treatment Among 1,063 patients with MDD who received Citalopram at doses ranging from 10 mg to 80 mg once daily in placebo- controlled trials of up to 6 weeks duration, 16% discontinued treatment due to an adverse reaction, as compared to 8% of 446 patients receiving placebo. The adverse reactions associated with discontinuation (i.e., associated with discontinuation in at least 1% of Citalopram-treated patients at a rate at least twice that of placebo) are shown in Table 2. Table 2: Adverse Reactions Associated with Discontinuation of Citalopram Treatment in Short-Term, Placebo-Controlled MDD Trials * A patient can report more than one reason for discontinuation and be counted more than once in this table. Body System/Adverse Reaction Citalopram Placebo (N=1,063) % (N=446) % General Asthenia 1 <1 Gastrointestinal Disorders Nausea 4 0 Dry Mouth 1 <1 Vomiting 1 0 Central and Peripheral Nervous System Disorders Dizziness 2 <1 Psychiatric Disorders Insomnia 3 1 Somnolence 2 1 Agitation 1 <1 Table 3 enumerates the incidence of adverse reactions that occurred among 1,063 patients with MDD who received Citalopram at doses ranging from 10 mg to 80 mg once daily in placebo-controlled trials of up to 6 weeks duration. The most common adverse reaction that occurred in Citalopram -treated patients with an incidence of 5% or greater and atleast twice the incidence in placebo patients was ejaculation disorder (primarily ejaculatory delay) in male patients (see Table 3). Table 3: Adverse Reactions (≥2% and Greater than Placebo) Among Citalopram -Treated Patients* *Adverse reactions reported by at least 2% of patients treated with Citalopram are reported, except for the following adverse reactions which had an incidence on placebo ≥ Citalopram: headache, asthenia, dizziness, constipation, palpitation,vision abnormal, sleep disorder, nervousness, pharyngitis, micturition disorder, back pain. 1 Denominator used was for females only (N=638 Citalopram; N=252 placebo). 2 Primarily ejaculatory delay. 3 Denominator used was for males only (N=425 Citalopram; N=194 placebo). Body System/Adverse Reaction Citalopram Placebo (N=1,063) % (N=446) % Gastrointestinal Disorders Nausea 21 14 Diarrhea 8 5 Dyspepsia 5 4 Vomiting 4 3 Abdominal Pain 3 2 Autonomic Nervous System Disorders Dry Mouth 20 14 Sweating Increased 11 9 Psychiatric Disorders Somnolence 18 10 Insomnia 15 14 Anxiety 4 3 Anorexia 4 2 Agitation 3 1 Dysmenorrhea1 3 2 Libido Decreased 2 <1 Yawning 2 <1 Central & Peripheral Nervous System Disorders Tremor 8 6 Urogenital Ejaculation Disorder 2,3 6 1 Impotence 3 3 <1 Respiratory System Disorders Upper Respiratory Tract Infection 5 4 Rhinitis 5 3 Sinusitis 3 <1 General Fatigue 5 3 Fever 2 <1 Musculoskeletal System Disorders Arthralgia 2 1 Myalgia 2 1 Dose Dependent Adverse Reactions The potential relationship between the dosage of Citalopram and the incidence of adverse reactions was examined in a fixed-dose study in patients with MDD receiving placebo or Citalopram 10 mg, 20 mg 40 mg, or 60 mg (1.5 times the maximum recommended dosage). A positive dose response (p<0.05) was revealed for the following adverse reactions: fatigue, impotence, insomnia, increased sweating, somnolence, and yawning. Male and Female Sexual Dysfunction with SSRIs 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.
Drug interactions
Table 5 presents clinically important drug interactions with Citalopram. CYP2C19 Inhibitors : Citalopram 20 mg daily is the maximum recommended dosage for patients taking concomitant CYP2C19 inhibitors ( 5.2 , 7.1 ). Table 5: Clinically Important Drug Interactions with Citalopram Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of SSRIs, including Citalopram, and MAOIs increases the risk of serotonin syndrome. Intervention Citalopram is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.5 ), 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 ( 12.2 )]. Intervention: Citalopram is contraindicated in patients taking pimozide [see Contraindications( 4 ), Warnings and Precautions ( 5.2 )]. Drugs that Prolong the QTc Interval Clinical Impact: Concomitant use of Citalopram with drugs that prolong QT can cause additional QT prolongation compared to the use of Citalopram alone [see Clinical Pharmacology ( 12.2 )]. Intervention: Avoid concomitant use of Citalopram with drugs that prolong the QT interval (Citalopram is contraindicated in patients taking pimozide) [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )]. CYP2C19 Inhibitors Clinical Impact: Concomitant use of Citalopram with CYP2C19 inhibitors increases the risk of QT prolongation and/or ventricular arrhythmias compared to the use of Citalopram alone [see Clinical Pharmacology ( 12.2 )]. Intervention: The maximum recommended dosage of Citalopram is 20 mg daily when used concomitantly with a CYP2C19 inhibitor [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.2 )]. Other Serotonergic Drugs Clinical Impact: Concomitant use of Citalopram and other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) increases the risk of serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during Citalopram initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of Citalopram and/or concomitant serotonergic drugs [see Warning and Precautions ( 5.3 )]. Drugs That Interfere With Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact: Concomitant use of Citalopram and an antiplatelet or anticoagulant may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of Citalopram and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warning and Precautions ( 5.4 )].
Use in specific populations
Pregnancy: SSRI use, particularly late in pregnancy, may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulties, hypotonia, tremor, irritability) in the neonate. ( 8.1 ). 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healhcare providers are encouraged to advise patients to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https:// womensmentalhealth.org/research/pregnancyregistry/antidepressants. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.4 ) and Clinical Considerations]. Available data from published epidemiologic studies and postmarketing reports with citalopram use in pregnancy have not established an increased risk of major birth defects or miscarriage. Published studies demonstrated that citalopram levels in both cord blood and amniotic fluid are similar to those observed in maternal serum. There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including Citalopram, during pregnancy . There also are risks associated with untreated depression in pregnancy (see Clinical Considerations) . In animal reproduction studies, citalopram caused adverse embryo/fetal effects at doses that caused maternal toxicity (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 and/or Embryo/Fetal Risk Women who discontinue antidepressants during pregnancy 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 depressive disorder 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. Maternal Adverse Reactions Use of Citalopram in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.4 )]. Fetal/Neonatal Adverse Reactions Neonates exposed to Citalopram and other SSRIs 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 findings are consistent with either a direct toxic effect of SSRIs 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 ( 5.3 )] . Data Human Data Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1- 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Citalopram was administered orally to pregnant rats during the period of organogenesis at doses of 32, 56, and 112 mg/kg/day, which are approximately 8, 14, and 27 times the Maximum Recommended Human Dose (MRHD) of 40 mg, based on mg/m 2 body surface area. Citalopram caused maternal toxicity of CNS clinical signs and decreased weight gain at 112 mg/kg/day, which is 27 times the MRHD. At this maternally toxic dose, citalopram decreased embryo/fetal growth and survival and increased fetal abnormalities (including cardiovascular and skeletal defects). The no observed adverse effect level (NOAEL) for maternal and embryofetal toxicity is 56 mg/kg/day, which is approximately 14 times the MRHD. Citalopram was administered orally to pregnant rabbits during the period of organogenesis at doses up to 16 mg/kg/day, which is approximately 8 times the MRHD of 40 mg, based on mg/m 2 body surface area. No maternal or embryofetal toxicity was observed. The NOAEL for maternal and embryofetal toxicity is 16 mg/kg/day, which is approximately 8 times the MRHD. Citalopram was administered orally to pregnant rats during late gestation and lactation periods at doses of 4.8, 12.8, and 32 mg/kg/day, which are approximately 1, 3, and 8 times the MRHD of 40 mg, based on mg/m 2 body surface area. Citalopram increased offspring mortality during the first 4 days of birth and decreased offspring growth at 32 mg/kg/day, which is approximately 8 times the MRHD. The NOAEL for developmental toxicity is 12.8 mg/kg/day, which is approximately 3 times the MRHD. In a separate study, similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, which is approximately 6 times the MRHD. A NOAEL was not determined in that study.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healhcare providers are encouraged to advise patients to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https:// womensmentalhealth.org/research/pregnancyregistry/antidepressants. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.4 ) and Clinical Considerations]. Available data from published epidemiologic studies and postmarketing reports with citalopram use in pregnancy have not established an increased risk of major birth defects or miscarriage. Published studies demonstrated that citalopram levels in both cord blood and amniotic fluid are similar to those observed in maternal serum. There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including Citalopram, during pregnancy . There also are risks associated with untreated depression in pregnancy (see Clinical Considerations) . In animal reproduction studies, citalopram caused adverse embryo/fetal effects at doses that caused maternal toxicity (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 and/or Embryo/Fetal Risk Women who discontinue antidepressants during pregnancy 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 depressive disorder 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. Maternal Adverse Reactions Use of Citalopram in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.4 )]. Fetal/Neonatal Adverse Reactions Neonates exposed to Citalopram and other SSRIs 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 findings are consistent with either a direct toxic effect of SSRIs 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 ( 5.3 )] . Data Human Data Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1- 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Citalopram was administered orally to pregnant rats during the period of organogenesis at doses of 32, 56, and 112 mg/kg/day, which are approximately 8, 14, and 27 times the Maximum Recommended Human Dose (MRHD) of 40 mg, based on mg/m 2 body surface area. Citalopram caused maternal toxicity of CNS clinical signs and decreased weight gain at 112 mg/kg/day, which is 27 times the MRHD. At this maternally toxic dose, citalopram decreased embryo/fetal growth and survival and increased fetal abnormalities (including cardiovascular and skeletal defects). The no observed adverse effect level (NOAEL) for maternal and embryofetal toxicity is 56 mg/kg/day, which is approximately 14 times the MRHD. Citalopram was administered orally to pregnant rabbits during the period of organogenesis at doses up to 16 mg/kg/day, which is approximately 8 times the MRHD of 40 mg, based on mg/m 2 body surface area. No maternal or embryofetal toxicity was observed. The NOAEL for maternal and embryofetal toxicity is 16 mg/kg/day, which is approximately 8 times the MRHD. Citalopram was administered orally to pregnant rats during late gestation and lactation periods at doses of 4.8, 12.8, and 32 mg/kg/day, which are approximately 1, 3, and 8 times the MRHD of 40 mg, based on mg/m 2 body surface area. Citalopram increased offspring mortality during the first 4 days of birth and decreased offspring growth at 32 mg/kg/day, which is approximately 8 times the MRHD. The NOAEL for developmental toxicity is 12.8 mg/kg/day, which is approximately 3 times the MRHD. In a separate study, similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, which is approximately 6 times the MRHD. A NOAEL was not determined in that study.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of Citalopram have not been established in pediatric patients. Two placebo-controlled trials in 407 pediatric patients with MDD have been conducted with Citalopram, and the data were not sufficient to support use in pediatric patients. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning , Warnings and Precautions ( 5.1 )] . Decreased appetite and weight loss have been observed in association with the use of SSRIs in pediatric patients.
Geriatric use
8.5 Geriatric Use Of 4422 patients in clinical studies of Citalopram, 1357 were 60 and over, 1034 were 65 and over, and 457 were 75 and over. In two pharmacokinetic studies, citalopram AUC was increased by 23% and 30%, respectively, in subjects ≥ 60 years of age as compared to younger subjects, and its half-life was increased by 30% and 50%, respectively [see Clinical Pharmacology ( 12.3 )]. Therefore, the maximum recommended dosage in patients 60 years of age and older is lower than younger patients [see Dosage and Administration ( 2.3 ),Warnings and Precautions ( 5.2 )] . SSRIs, i ncluding Citalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions ( 5.9 )] .
Overdosage
The following have been reported with Citalopram tablet overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, and torsade de pointes. Hypertension most commonly seen, but rarely can see hypotension alone or with co‐ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Prolonged cardiac monitoring is recommended in Citalopram overdosage ingestions due to the arrhythmia risk. Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a Citalopram overdose. Consider contacting a Poison Center (1‐800‐221‐2222) or a medical toxicologist for additional overdosage management recommendations.
Description
Citalopram tablet contains citalopram hydrobromide, an orally administered selective serotonin reuptake inhibitor (SSRI) with a chemical structure unrelated to that of other SSRIs or of tricyclic, tetracyclic, or other available antidepressant agents. Citalopram hydrobromide is a racemic bicyclic phthalane derivative designated (±)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3- dihydroisobenzofuran-5-carbonitrile, hydrobromide with the following structural formula: The molecular formula is C 20 H 22 BrFN 2 O and its molecular weight is 405.35. Citalopram hydrobromide occurs as a fine, white to off-white powder. Citalopram hydrobromide is sparingly soluble in water and soluble in ethanol. Citalopram is available only in tablet dosage form. Citalopram tablets, USP 10 mg are film-coated, round tablets containing citalopram hydrobromide in strengths equivalent to 10 mg citalopram base. Citalopram hydrobromide, USP 20 mg and 40 mg tablets are film-coated, round, scored tablets containing citalopram hydrobromide in strengths equivalent to 20 mg or 40 mg citalopram base. Their strengths reflect their citalopram base equivalent content. The 10 mg, 20 mg and 40 mg strength tablets contain 12.49 mg, 24.98 mg and 49.96 mg of citalopram hydrobromide, respectively. The tablets also contain the following. Inactive ingredients : copovidone, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, opadry beige (HPMC 2910/hypromellose 6cp, titanium dioxide, macrogol/Peg400, iron oxide yellow and iron oxide red), opadry pink (HPMC 2910/hypromellose 6cP, titanium dioxide, macrogol/Peg400 and iron oxide red) and opadry white (titanium dioxide, HPMC 2910/hypromellose 3cp, HPMC 2910/ hypromellose 6cp, Macrogol/Peg400 and Polysorbate 80) are used as coloring agents in the beige (10 mg) and pink (20 mg) and white (40 mg) tablets. Image
Mechanism of action
12.1 Mechanism of Action The mechanism of action of citalopram is unclear, but is presumed to be related to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).
How supplied
Citalopram Tablets, USP 10 mg: They are supplied in Bottle of 30 NDC # 76282-628-30, Bottle of 90 NDC # 76282-628-90, Bottle of 500 NDC # 76282-628-05 and Bottle of 1,000 NDC # 76282-628-10 Beige, film coated round, bi-convex tablets debossed with IG on one side and “206” on the other. 20 mg: They are supplied in Bottle of 30 NDC # 76282-629-30, Bottle of 90 NDC # 76282-629-90, Bottle of 500 NDC # 76282-629-05 and Bottle of 1,000 NDC # 76282-629-10 Pink, film coated, round, bi-convex tablets debossed with I on the left side of bisect and G on right side of bisect on one side and “207” on the other. 40 mg: They are supplied in Bottle of 30 NDC # 76282-208-30, Bottle of 90 NDC # 76282-208-90, Bottle of 500 NDC # 76282-208-05 and Bottle of 1,000 NDC # 76282-208-10 White, film coated, round, bi-convex tablets debossed with I on the left side of bisect and G on right side of bisect on one side and “208” on the other. Storage and Handling Citalopram tablets should be stored at 20-25°C (68 to 77°F); excursions permitted between 15 and 30°C (59-86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down and instruct them to report such symptoms to the healthcare provider. [see Boxed Warning, Warnings and Precautions ( 5.1 )]. QT Prolongation and Torsade de Pointes Advise patients to consult their health care provider immediately if they feel faint, lose consciousness, or have heart palpitations. Instruct patients to inform their health care provider that they are taking Citalopram before taking any new medications [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7 )]. Serotonin Syndrome Caution patients about the the risk of serotonin syndrome, particularly with the concomitant use of Citalopram with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, 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). Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )]. Increased Risk of Bleeding Inform patients about the concomitant use of Citalopram with aspirin, NSAIDs, other antiplatelet drugs,warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the counter medications that increase the risk of bleeding [see Warnings and Precautions ( 5.4 )]. 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 )]. Discontinuation Syndrome Advise patients not to abruptly discontinue Citalopram and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when Citalopram is discontinued [See Warnings and Precautions( 5.6 )]. Sexual Dysfunction Advise patients that use of Citalopram 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 ( 5.10 )]. Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with Citalopram [see Use in Specific Populations ( 8.1 )]. Advise patients that Citalopram use late in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN) [see Use in Specific Populations ( 8.1 )]. Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to citalopram during pregnancy [see Use in Specific Populations ( 8.1 )]. Lactation Advise breastfeeding women 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 )] . Revised: 08/2024
Label text from the FDA structured product label by Exelan Pharmaceuticals Inc. (revised Aug 1, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Citalopram Hydrobromide in 29 products
Citalopram Hydrobromide NDC products (29)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-3208 | Citalopram Hydrobromide 40 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-6846 | Citalopram Hydrobromide 20 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-6947 | Citalopram Hydrobromide 40 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 80425-0309 | Citalopram Hydrobromide 10 mg/1 Tablet, Film Coated | Advanced Rx Pharmacy of Tennessee, LLC | ANDA |
| 43353-112 | Citalopram Hydrobromide 40 mg/1 Tablet | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-092 | Citalopram Hydrobromide 20 mg/1 Tablet | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 17856-0564 | Citalopram Hydrobromide 10 mg/5mL Solution | ATLANTIC BIOLOGICALS CORP. | ANDA |
| 65862-074 | Citalopram Hydrobromide 10 mg/5mL Solution | Aurobindo Pharma Limited | ANDA |
| 71335-0480 | Citalopram Hydrobromide 40 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-0238 | Citalopram Hydrobromide 20 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 31722-564 | Citalopram Hydrobromide 10 mg/5mL Solution | Camber Pharmaceuticals, Inc. | ANDA |
| 76282-629 | Citalopram Hydrobromide 20 mg/1 Tablet | Exelan Pharmaceuticals Inc. | ANDA |
| 76282-628 | Citalopram Hydrobromide 10 mg/1 Tablet | Exelan Pharmaceuticals Inc. | ANDA |
| 76282-208 | Citalopram Hydrobromide 40 mg/1 Tablet | Exelan Pharmaceuticals Inc. | ANDA |
| 51655-043 | Citalopram Hydrobromide 10 mg/1 Tablet, Film Coated | Northwind Health Company, LLC | ANDA |
| 68071-2198 | Citalopram Hydrobromide 20 mg/1 Tablet | NuCare Pharmaceuticals, Inc. | ANDA |
| 68071-1830 | Citalopram Hydrobromide 20 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-5132 | Citalopram Hydrobromide 20 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-3384 | Citalopram Hydrobromide 40 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-2459 | Citalopram Hydrobromide 10 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-1906 | Citalopram Hydrobromide 20 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA |
| 68788-8962 | Citalopram Hydrobromide 40 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals Inc. | ANDA |
| 68788-0802 | Citalopram Hydrobromide 20 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals, Inc. | ANDA |
| 68788-9692 | Citalopram Hydrobromide 10 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals, Inc. | ANDA |
| 71205-764 | Citalopram Hydrobromide 40 mg/1 Tablet | Proficient Rx LP | ANDA |
| 63187-203 | Citalopram Hydrobromide 20 mg/1 Tablet | Proficient Rx LP | ANDA |
| 63187-220 | Citalopram Hydrobromide 10 mg/1 Tablet | Proficient Rx LP | ANDA |
| 55700-851 | Citalopram Hydrobromide 20 mg/1 Tablet | Quality Care Products, LLC | ANDA |
| 55700-787 | Citalopram Hydrobromide 10 mg/1 Tablet | Quality Care Products, LLC | ANDA |
Frequently asked questions
What is Citalopram Hydrobromide used for?
Citalopram is indicated for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies ( 14 )] . Citalopram is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD) in adults ( 1 ).
What are the side effects of Citalopram Hydrobromide?
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 adolescents 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 )]… See the full label for the complete list.
Who makes Citalopram Hydrobromide?
Citalopram Hydrobromide is listed by 15 labelers in the FDA NDC directory, including A-S Medication Solutions, Advanced Rx Pharmacy of Tennessee, LLC, Aphena Pharma Solutions - Tennessee, LLC, ATLANTIC BIOLOGICALS CORP..