Generic Name: Citalopram
Brand Names: • Celexa • Cipramil
Class: Antidepressant, Serotonin Reuptake Inhibitor
Updated: July 2014
What Is It?
CELEXA® (citalopram HBr) is an orally administered selective serotonin reuptake inhibitor (SSRI). CELEXA is distributed by Forest Pharmaceuticals, Inc., and licensed from H. Lundbeck A/S.
CELEXA is indicated and approved by the FDA for the treatment of:
• major depressive disorder
Off-label uses include the treatment of:
• generalized anxiety disorder (GAD)
• panic disorder
• obsessive-compulsive disorder (OCD)
• premenstrual dysphoric disorder.
Celexa may have other uses not mentioned in this abridged medication guide. The efficacy of Celexa in maintaining an antidepressant response for up to 24 weeks following 6 to 8 weeks of acute treatment was demonstrated in two placebo-controlled trials.
Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using Celexa. Your family or other caregivers should also be alert to changes in your mood or symptoms.
This medication guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about.
Do not start or stop any medicine while taking CELEXA without talking to your healthcare provider first.
Who Should Not Take Celexa?
Do not take Celexa if you: 1) are allergic to citalopram hydrobromide or escitalopram oxalate. See the end of this section for a complete list of ingredients in CELEXA; or 2) take a monoamine oxidase inhibitor (MAOI) or have taken an MAOI in the past 14 days. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 2 weeks of stopping Celexa unless directed to do so by your physician. Do not start Celexa if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician. MAOIs include Parnate (Tranylcypromine), Nardil (Phenelzine), Emsam (Selegiline transdermal), and Marplan (Isocarboxazid).
Do not give Celexa to anyone younger than 18 years old without the advice of a doctor.
Before Starting Celexa
Tell your healthcare provider about: 1) any medical or psychiatric conditions you have, including cardiac, liver, kidney, or blood disease, seizures, or bipolar disorder; 2) current pregnancy or plans to become pregnant; 3) current breastfeeding or plans to breastfeed; 4) any and all medications and supplements you are taking; 5) any thoughts or feelings of suicide. Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.
Patients should be told that the concomitant use of CELEXA and alcohol is not advised. Patients should 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. Patients should notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should notify their physician if they are breast feeding an infant. While patients may notice improvement with CELEXA therapy, they should be advised to continue therapy as directed.
Ingredients of CELEXA:
Active ingredient: citalopram hydrobromide. Inactive ingredients: Tablets: copolyvidone, corn starch, crosscarmellose sodium, glycerin, lactose monohydrate, magnesium stearate, hypromellose, microcrystalline cellulose, polyethylene glycol, titanium dioxide and iron dioxide for coloring.
Indications and Usage
Celexa is indicated for the treatment of major depressive disorder (MDD). Off-label uses of Celexa include fibromyalgia, generalized anxiety disorder (GAD), panic disorder, obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder. Celexa may have other uses not mentioned in this abridged medication guide.
A major depressive episode (DSM-V) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. The antidepressant action of Celexa in hospitalized depressed patients has not been adequately studied. The efficacy of Celexa in maintaining an antidepressant response for up to 24 weeks following 6 to 8 weeks of acute treatment was demonstrated in two placebo-controlled trials. Nevertheless, the physician who elects to use Celexa for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
The physician who elects to use Celexa for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
The use of MAOIs intended to treat psychiatric disorders with Celexa or within 14 days of stopping treatment with Celexa is contraindicated because of an increased risk of serotonin syndrome. The use of Celexa within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated.
Starting Celexa in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome.
Concomitant use in patients taking pimozide is contraindicated.
Celexa is contraindicated in patients with a hypersensitivity to citalopram or any of the inactive ingredients in Celexa.
Common Side Effects with percent reported
Dermatologic: Diaphoresis (5% to 18% )
Gastrointestinal: Constipation (13% ), Diarrhea (8% ), Nausea (20% to 21% ), Vomiting (4% to 20% ), Xerostomia (17% to 20% )
Neurologic: Dizziness (up to 14%), Headache (up to 18% ), Insomnia (15%), Sedated (15% ), Somnolence (18% ), Tremor (8% to 16% )
Psychiatric: Agitation (3% to 10% )
Reproductive: Disorder of ejaculation (6.1% )
Other: Fatigue (5% )
Serious Side Effects with percent reported
Cardiovascular: Myocardial infarction (0.1% to 1%), Prolonged QT interval (0.5% to 1.9% ), Torsades de pointes
Neurologic: Cerebrovascular accident (0.1% to 1%)
Psychiatric: Depression, worsening (rare), Suicidal thoughts, Suicide
Other: Serotonin syndrome
Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Suicidality and Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Celexa or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Celexa is not approved for use in pediatric patients. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.
Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Families and caregivers of patients being treated with antidepressants for Major Depressive Disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.
In clinical trials of citalopram, there were reports of citalopram overdose, including overdoses of up to 2000mg, with no associated fatalities. During the postmarketing evaluation of citalopram, Celexa overdoses, including overdoses of up to 6000 mg, have been reported. As with other SSRIs, a fatal outcome in a patient who has taken an overdose of citalopram has been rarely reported. Symptoms most often accompanying citalopram overdose, alone or in combination with other drugs and/or alcohol, included dizziness, sweating, nausea, vomiting, tremor, somnolence, and sinus tachycardia. In more rare cases, observed symptoms included amnesia, confusion, coma, convulsions, hyperventilation, cyanosis, rhabdomyolysis, and ECG changes (including QTc prolongation, nodal rhythm, ventricular arrhythmia, and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose.
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women; therefore, citalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Neonates exposed to Celexa and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the 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.
In animal reproduction studies, citalopram has been shown to have adverse effects on embryo/fetal and postnatal development, including teratogenic effects, when administered at doses greater than human therapeutic doses. In two rat embryo/fetal development studies, oral administration of 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 maximum recommended human dose (MRHD) of 60 mg/day on a body surface area (mg/m ) basis. This dose was also associated with maternal toxicity (clinical signs, decreased BW gain). The developmental no effect dose of 56 mg/kg/day is approximately 9 times the MRHD on a mg/m basis. In a rabbit study, no adverse effects on embryo/fetal development were observed at doses of up to 16 mg/kg/day, or approximately 5 times the MRHD on mg/m2 basis. Thus, teratogenic effects were observed at a maternally toxic dose in the rat and were not observed in the rabbit.
Labor and Delivery
The effect of Celexa on labor and delivery in humans is unknown.
As has been found to occur with many other drugs, citalopram is excreted in human breast milk. There have been two reports of infants experiencing excessive somnolence, decreased feeding, and weight loss in association with breastfeeding from a citalopram-treated mother; in one case, the infant was reported to recover completely upon discontinuation of citalopram by its mother and in the second case, no follow-up information was available. The decision whether to continue or discontinue either nursing or Celexa therapy should take into account the risks of citalopram exposure for the infant and the benefits of Celexa treatment for the mother.
Of 4422 patients in clinical studies of Celexa, 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 greater sensitivity of some older individuals cannot be ruled out. Most elderly patients treated with Celexa in clinical trials received daily doses between 20 and 40 mg. SSRIs and SNRIs, including Celexa, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event. 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. 20 mg/day is the maximum recommended dose for patients who are greater than 60 years of age.
Celexa® (citalopram HBr) is 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 HBr is a racemic bicyclic phthalane derivative designated (±)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5 carbonitrile, HBr. The molecular formula is C20H22BrFN2O and its molecular weight is 405.35. Citalopram HBr occurs as a fine, white to off-white powder. Citalopram HBr is sparingly soluble in water and soluble in ethanol. Celexa (citalopram hydrobromide) is available only in tablet dosage form. Celexa 10 mg are film-coated, oval tablets containing citalopram HBr in strengths equivalent to 10 mg citalopram base. Celexa 20 mg and 40 mg are film-coated, oval, scored tablets containing citalopram HBr in strengths equivalent to 20 mg or 40 mg citalopram base. The tablets also contain the following inactive ingredients: copolyvidone, corn starch, crosscarmellose sodium, glycerin, lactose monohydrate, magnesium stearate, hypromellose, microcrystalline cellulose, polyethylene glycol, and titanium dioxide. Iron oxides are used as coloring agents in the beige (10 mg) and pink (20 mg) tablets.
The mechanism of action of citalopram HBr as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). In vitro and in vivo studies in animals suggest that citalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake. Tolerance to the inhibition of 5-HT uptake is not induced by long-term (14-day) treatment of rats with citalopram. Citalopram is a racemic mixture (50/50), and the inhibition of 5-HT reuptake by citalopram is primarily due to the (S)-enantiomer. Citalopram has no or very low affinity for 5-HT1A, 5-HT2A, dopamine D1 and D2, α1-, α2-, and β adrenergic, histamine H1, gamma aminobutyric acid (GABA), muscarinic cholinergic, and benzodiazepine receptors. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects of other psychotropic drugs.
The single- and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in a dose range of 10-60 mg/day. Biotransformation of citalopram is mainly hepatic, with a mean terminal half-life of about 35 hours. With once daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of citalopram in plasma, based on the half-life, is expected to be 2.5 times the plasma concentrations observed after a single dose. Absorption and Distribution Following a single oral dose (40 mg tablet) of citalopram, peak blood levels occur at about 4 hours. The absolute bioavailability of citalopram was about 80% relative to an intravenous dose, and absorption is not affected by food. The volume of distribution of citalopram is about 12 L/kg and the binding of citalopram (CT), demethylcitalopram (DCT) and didemethylcitalopram (DDCT) to human plasma proteins is about 80%.
Absorption and Distribution
Following a single oral dose (40 mg tablet) of citalopram, peak blood levels occur at about Celexa (citalopram HBr) hours. The absolute bioavailability of citalopram was about 80% relative to an intravenous dose, and absorption is not affected by food. The volume of distribution of citalopram is about 12 L/kg and the binding of citalopram (CT), demethylcitalopram (DCT) and didemethylcitalopram (DDCT) to human plasma proteins is about 80%.
Metabolism and Elimination
Following intravenous administrations of citalopram, the fraction of drug recovered in the urine as citalopram and DCT was about 10% and 5%, respectively. The systemic clearance of citalopram was 330 mL/min, with approximately 20% of that due to renal clearance. Citalopram is metabolized to demethylcitalopram (DCT), didemethylcitalopram (DDCT), citalopram-N-oxide, and a deaminated propionic acid derivative. In humans, unchanged citalopram is the predominant compound in plasma. At steady state, the concentrations of citalopram’s metabolites, DCT and DDCT, in plasma are approximately one-half and one-tenth, respectively, that of the parent drug. In vitro studies show that citalopram is at least 8 times more potent than its metabolites in the inhibition of serotonin reuptake, suggesting that the metabolites evaluated do not likely contribute significantly to the antidepressant actions of citalopram. In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of citalopram.
Drug-Drug Interactions Including P450 Interactions
In vitro enzyme inhibition data did not reveal an inhibitory effect of citalopram on CYP3A4, 2C9, or -2E1, but did suggest that it is a weak inhibitor of CYP1A2, -2D6, and -2C19. Citalopram would be expected to have little inhibitory effect on in vivo metabolism mediated by these enzymes. However, in vivo data to address this question are limited. CYP3A4 and CYP 2C19 inhibitors: Since CYP3A4 and CYP 2C19 are the primary enzymes involved in the metabolism of citalopram, it is expected that potent inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, and macrolide antibiotics) and potent inhibitors of CYP2C19 (e.g., omeprazole) might decrease the clearance of citalopram. However, coadministration of citalopram and the potent CYP3A4 inhibitor ketoconazole did not significantly affect the pharmacokinetics of citalopram. Celexa 20 mg/day is the maximum recommended dose in patients taking concomitant cimetidine or another CYP2C19 inhibitor, because of the risk of QT prolongation. CYP2D6 Inhibitors: Coadministration of a drug that inhibits CYP2D6 with Celexa is unlikely to have clinically significant effects on citalopram metabolism, based on the study results in CYP2D6 poor metabolizers.
Dosage and Administration
• 10 mg Bottle of 100 NDC # 0456-4010-01, Beige, oval, film-coated. Imprint on one side with “FP”. Imprint on the other side with “10 mg”.
• 20 mg Bottle of 100 NDC # 0456-4020-01, 10 x 10 Unit Dose NDC # 0456-4020-63, Pink, oval, scored, film-coated. Imprint on scored side with “F” on the left side and “P” on the right side. Imprint on the non-scored side with “20 mg”.
• 40 mg Bottle of 100 NDC # 0456-4040-01, 10 x 10 Unit Dose NDC # 0456-4040-63, White, oval, scored, film-coated. Imprint on scored side with “F” on the left side and “P” on the right side. Imprint on the non-scored side with “40 mg”.
Celexa should be administered once daily, in the morning or evening, with or without food.
Major Depressive Disorder
Initial Treatment: Celexa (citalopram HBr) should be administered at an initial dose of 20 mg once daily, with an increase to a maximum dose of 40 mg/day at an interval of no less than one week. Doses above 40 mg/day are not recommended due to the risk of QT prolongation. Additionally, the only study pertinent to dose response for effectiveness did not demonstrate an advantage for the 60 mg/day dose over the 40 mg/day dose.
20 mg/day is the maximum recommended dose for patients who are greater than 60 years of age, patients with hepatic impairment, and for CYP2C19 poor metabolizers or those patients taking cimetidine or another CYP2C19 inhibitor. No dosage adjustment is necessary for patients with mild or moderate renal impairment. Celexa should be used with caution in patients with severe renal impairment.
Treatment of Pregnant Women During the Third Trimester
Neonates exposed to Celexa and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with Celexa during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.
It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacologic therapy. Systematic evaluation of Celexa in two studies has shown that its antidepressant efficacy is maintained for periods of up to 24 weeks following 6 or 8 weeks of initial treatment (32 weeks total). In one study, patients were assigned randomly to placebo or to the same dose of Celexa (20-60 mg/day) during maintenance treatment as they had received during the acute stabilization phase, while in the other study, patients were assigned randomly to continuation of Celexa 20 or 40 mg/day, or placebo, for maintenance treatment. In the latter study, the rates of relapse to depression were similar for the two dose groups. Based on these limited data, it is not known whether the dose of citalopram needed to maintain euthymia is identical to the dose needed to induce remission. If adverse reactions are bothersome, a decrease in dose to 20 mg/day can be considered.
Discontinuation of Treatment with Celexa
Symptoms associated with discontinuation of Celexa and other SSRIs and SNRIs have been reported. 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.