Celexa

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

• dizziness
• sweating
• nausea
• vomiting
• uncontrollable shaking of a part of the body
• drowsiness
• fast, irregular, or pounding heartbeat
• memory loss
• confusion
• seizures
• coma (loss of consciousness)
• fast breathing
• bluish color around mouth, fingers, or fingernails
• muscle pain
• dark-colored urine

Yes, a prescription is needed.

GENERIC AVAILABLE: Yes

Celexa

Tablets: 10, 20, and 40 mg. Solution: 10 mg/5 ml

Citalopram should be stored at room temperature, 15 to 30 C (59 to 86 F).

Black Box Warnings

In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses

This increase was not seen in patients >24 years; a slight decrease in suicidal thinking was seen in adults >65 years

In children and young adults, the risks must be weighed against the benefits of taking antidepressants

Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments

The patient’s family should communicate any abrupt changes in behavior to the health-care provider

Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy

Not FDA approved for the treatment of bipolar disorder

This drug is not FDA approved for use in pediatric patients

Contraindications

Hypersensitivity

Coadministration with pimozide

Coadministration with serotonergic drugs

• Concomitant use or within 14 days of MAOIs increases risk of serotonin syndrome
• Symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma
• Starting citalopram in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome
• If linezolid or IV methylene blue must be administered, discontinue SSRI immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring (5 weeks for fluoxetine), whichever comes first

Cautions

Pregnancy: Conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn, or PPHN (see Pregnancy)

Neonates exposed to SNRIs/SSRIs late in third trimester: Risk of complications such as feeding difficulties, irritability, and respiratory problems

Clinical worsening and suicide ideation may occur despite medication in adolescents and young adults (18-24 years)

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

Risk of hyponatremia, abnormal bleeding (increased if concomitant aspirin, NSAIDs, or anticoagulants, or hemorrhagic diathesis), and impairment of cognitive and motor functions

Risk of serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with SSRIs alone or with concomitant use of serotonergic drugs, with drugs that impair metabolism of serotonin, or with antipsychotics or other dopamine antagonists

Activation of mania/hypomania has been reported; use caution when treating patients with history of mania

Increased risk of bone fractures reported with antidepressant use; use caution; consider possibility of fracture it patient presents with bone pain

May cause or exacerbate sexual dysfunction

Use caution when treating patients with history of seizure disorder

Rare cases of hyponatremia and development of SIADH reported with either SSRI or SNRI use

Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort

Not recommended in patients with uncompensated heart failure

QT prolongation

• Dose-dependent QT prolongation reported; do not exceed dose of 40 mg/day
• Correct hypokalemia and hypomagnesemia before initiating and monitor periodically
• ECG monitoring recommended in patients with CHF, bradyarrhythmias, or concomitant medications known to prolong QT interval
• Do not exceed 20 mg/day if administered in CYP2C19 poor metabolizers, or in patients taking concomitant cimetidine or another CYP2C19 inhibitor (eg, fluconazole, omeprazole)
• Do not exceed 20 mg/day in individuals aged 60 yr or older, or those with hepatic impairment

Celexa is a prescription medicine used to treat depression.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Celexa is part of the drug class:

• Selective serotonin reuptake inhibitors

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Celexa there are no specific foods that you must exclude from your diet when receiving Celexa.

• Your doctor will tell you how much of this medicine to take and how often.
• The typical dose for adults is 20-40 mg daily. A lower dose may need to be used if you are elderly or if you have liver problems.
• You may take this medicine with or without food.
• Your dose may need to be changed several times in order to find out what works best for you. Do not take more medicine or take it more often than your doctor tells you to.
• You may need to take this medicine for several weeks before you feel better. Keep taking the medicine as your doctor prescribes.

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. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Celexa is not approved for use in pediatric patients.

Contraindications

• Citalopram is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with an MAO inhibitor intended to treat psychiatric disorders.399 Conversely, MAO inhibitors intended to treat psychiatric disorders are contraindicated within 2 weeks of citalopram discontinuance.399 (See Serotonin Syndrome under Cautions and also see Specific Drugs under Interactions.)

• Initiation of citalopram is contraindicated in patients receiving MAO inhibitors such as linezolid or IV methylene blue.399 (See Specific Drugs under Interactions.)

• Concurrent pimozide therapy.1 (See Interactions.)

• Known hypersensitivity to citalopram, escitalopram, or any ingredient in the formulation.1 348 349 403

Warnings/Precautions

Warnings

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.370 371 376 399 However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.370 371 376

Appropriately monitor and closely observe patients receiving citalopram for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.370 371 376 399 (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.370 376 399 Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.370 371 376 399 If decision is made to discontinue therapy, taper citalopram dosage as rapidly as is feasible but consider risks of abrupt discontinuance.370 399 (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.370 399

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.370 399

Sensitivity Reactions

Possible anaphylaxis, allergic reactions, and angioedema.1

If hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated.1

Other Warnings and Precautions

Causes dose-dependent QTc-interval prolongation; postmarketing cases of torsades de pointes, ventricular tachycardia, and sudden death reported.399 416 417 418 419 420 421 424

Do not use citalopram dosages >40 mg daily.399 416 417 424 Use not recommended in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent AMI, or uncompensated heart failure.399 424 Do not use in patients receiving other drugs known to prolong the QTc interval.399 424 (See Interactions.)

Maximum dosage of 20 mg daily in patients who are poor metabolizers of CYP2C19 and in patients receiving a CYP2C19 inhibitor, patients with hepatic impairment, and in patients >60 years of age since higher citalopram exposures increase risk of QT-interval prolongation and torsades de pointes.399 424

In patients at risk for clinically important electrolyte disturbances, obtain baseline and periodic serum potassium and magnesium measurements.399 424 Correct hypokalemia and/or hypomagnesemia before citalopram administration because of increased risk of QTc-interval prolongation and arrhythmias.399 416 424 ECG monitoring recommended in patients in whom citalopram is not recommended but considered essential (e.g., patients with cardiac conditions mentioned above, those receiving other drugs known to prolong the QTc interval).399 424

Discontinue citalopram in patients with persistent QTc measurements >500 msec.399 424 If patient experiences symptoms indicating cardiac arrhythmias (e.g., dizziness, palpitations, syncope), initiate further evaluation, including cardiac monitoring.399 424

May unmask bipolar disorder.1 370 (See Activation of Mania or Hypomania under Cautions.) Citalopram is not approved for use in treating bipolar depression.1

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.1 370

Potentially life-threatening serotonin syndrome reported with SSRIs and SNRIs alone, but particularly during concurrent therapy with other serotonergic drugs (e.g., 5-HT1 receptor agonists [“triptans”], TCAs, buspirone, fentanyl, lithium, tramadol, tryptophan, St. John's wort [Hypericum perforatum]) and with drugs that impair the metabolism of serotonin (particularly MAO inhibitors, both those used to treat psychiatric disorders and others, such as linezolid and methylene blue).253 316 317 386 399 400 408 (See Interactions.)

Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).316 317 386 399 400 408

Citalopram is contraindicated in patients who are currently receiving or have recently (i.e., within 2 weeks) received therapy with MAO inhibitors intended to treat psychiatric disorders.399 Do not initiate citalopram in patients treated with other MAO inhibitors such as linezolid or IV methylene blue.399 (See Specific Drugs under Interactions.)

If concurrent therapy with other serotonergic drugs is clinically warranted, advise patient of potentially increased risk for serotonin syndrome, particularly during initiation of therapy and dosage increases.399

Monitor patients receiving citalopram for the development of serotonin syndrome.399 If manifestations occur, immediately discontinue citalopram and any concurrently administered serotonergic agents and initiate supportive and symptomatic treatment.399

Pupillary dilation (mydriasis) occurs with many antidepressants, including citalopram, and may trigger an acute attack of angle-closure glaucoma (narrow-angle glaucoma) in patients with anatomically narrow angles who do not have a patent iridectomy.399 (See Advice to Patients.)

Withdrawal effects (e.g., dysphoric mood, irritability, agitation, dizziness, sensory disturbances [e.g., paresthesias, such as electric shock sensations], anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania) reported following discontinuance of serotonergic antidepressants, particularly when discontinuance was abrupt.17 212 218 219 220 221 223 224 225 226 227 228 229 230 231 232 233 234 235 399 Events generally self-limiting, but serious cases reported.17 205 225 229 230 232 399

Possible increased risk of bleeding with SSRIs, including citalopram, and SNRIs; events ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.54 55 205 283 284 285 287 377 378 399 Concomitant use of aspirin, NSAIAs, warfarin, or other anticoagulants may increase risk.54 55 377 399 (See Drugs Affecting Hemostasis under Interactions and also see Advice to Patients.)

Possible hyponatremia during treatment with SSRIs, including citalopram, and SNRIs; in many cases, hyponatremia appears to be due to SIADH.8 9 206 207 208 344 363 399 Increased risk in patients who are volume depleted, elderly, or taking diuretics.201 202 203 204 205 208 209 210 344 363 399 Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.399

Possible activation of mania/hypomania; use with caution in patients with a history of mania.1 236 237 327 (See Bipolar Disorder under Cautions.)

Risk of seizures not systematically evaluated; use with caution in patients with a history of seizure disorder.1

Citalopram did not impair intellectual function or psychomotor performance in healthy individuals.399 However, any psychoactive drug may impair judgment, thinking, or motor skills.399 (See Advice to Patients.)

Limited experience with certain concurrent systemic diseases.399 (See QT-interval Prolongation and Torsades de Pointes under Cautions.)

Ensure accuracy of prescription; similarity in spelling of Celexa (citalopram hydrobromide), Celebrex (celecoxib), and Cerebyx (fosphenytoin sodium) may result in errors.346

Effects of concomitant use with ECT have not been systematically evaluated.1

Specific Populations

Category C.1

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care, reported in neonates exposed to citalopram, other SSRIs, or SNRIs late in the third trimester; may arise immediately upon delivery.212 213 380 381 382 383 399 (See General under Dosage and Administration.)

Conflicting findings from available studies evaluating possible risk of persistent pulmonary hypertension of the newborn (PPHN) following in utero exposure to SSRIs; currently unclear whether SSRI use during pregnancy can cause PPHN.399 600 601 602 603 604 605 606 610

Consult joint APA and ACOG guidelines (at ) for additional information on management of depression in women prior to conception and during pregnancy, including treatment algorithms.600 608

Effect on labor and delivery unknown.399

Distributed into milk;1 5 6 90 91 92 95 96 362 possible serious adverse reactions (e.g., excessive somnolence, decreased feeding, weight loss) in nursing infants.1 Discontinue nursing or the drug.1

Safety and efficacy not established in children <18 years of age.1 Results of 2 placebo-controlled trials in children and adolescents with major depressive disorder did not support a claim of efficacy for use of citalopram in pediatric patients with this condition.1 379

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).370 371 However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.398 No suicides occurred in these pediatric trials.370 398 399

Carefully consider these findings when assessing potential benefits and risks of citalopram in a child or adolescent for any clinical use.1 370 371 376 398 399 (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Decreased appetite and weight loss observed with use of SSRIs; monitor weight and growth regularly in children and adolescents treated with long-term citalopram therapy.399

No substantial differences in safety and efficacy relative to younger adults.399

Higher citalopram exposures may increase risk of QT-interval prolongation and torsades de pointes.83 85 399 424 (See Geriatric Patients under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Clinically important hyponatremia reported in geriatric patients, who may be at increased risk for this adverse effect.201 202 203 204 205 208 209 210 344 363 399 Some clinicians recommend periodic monitoring (especially during the first several months) of serum sodium concentrations in geriatric patients receiving SSRIs.207 208 209 344 348 349 (See Hyponatremia/SIADH under Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.370 371 399 (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Higher citalopram exposures may increase risk of QT-interval prolongation and torsades de pointes.1 4 399 424 Use with caution.399 424 (See Hepatic Impairment under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

Use with caution in patients with severe renal impairment.1 4 (See Renal Impairment under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Nausea, dry mouth, insomnia, sweating, sexual dysfunction (ejaculatory disorder, impotence, decreased libido), tremor, diarrhea, somnolence, dyspepsia, fatigue, upper respiratory tract infection, rhinitis.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• CeleXA

Available Dosage Forms:

• Tablet
• Solution

Therapeutic Class: Antidepressant

Pharmacologic Class: Serotonin Reuptake Inhibitor

General

During marketing of Celexa and other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.

Patients should be monitored for these symptoms when discontinuing treatment with Celexa. 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 (see DOSAGE AND ADMINISTRATION).

Abnormal Bleeding

SSRIs and SNRIs, including Celexa, 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 Celexa and NSAIDs, aspirin, or other drugs that affect coagulation.

Hyponatremia

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Celexa. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was reversible when Celexa was discontinued. Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk (see Geriatric Use). Discontinuation of Celexa should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.

Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.

Activation of Mania/Hypomania

In placebo-controlled trials of Celexa, some of which included patients with bipolar disorder, activation of mania/hypomania was reported in 0.2% of 1063 patients treated with Celexa and in none of the 446 patients treated with placebo. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorders treated with other marketed antidepressants. As with all antidepressants, Celexa should be used cautiously in patients with a history of mania.

Seizures

Although anticonvulsant effects of citalopram have been observed in animal studies, Celexa 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 Celexa, seizures occurred in 0.3% of patients treated with Celexa (a rate of one patient per 98 years of exposure) and 0.5% of patients treated with placebo (a rate of one patient per 50 years of exposure). Like other antidepressants, Celexa should be introduced with care in patients with a history of seizure disorder.

Interference with Cognitive and Motor Performance

In studies in normal volunteers, Celexa in doses of 40 mg/day did not produce impairment of intellectual function or psychomotor performance. Because any psychoactive drug may impair judgment, thinking, or motor skills, however, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Celexa therapy does not affect their ability to engage in such activities.

Use in Patients with Concomitant Illness

Clinical experience with Celexa in patients with certain concomitant systemic illnesses is limited. Due to the risk of QT prolongation, citalopram use should be avoided in patients with certain cardiac conditions, and ECG monitoring is advised if Celexa must be used in such patients. Electrolytes should be monitored in treating patients with diseases or conditions that cause hypokalemia or hypomagnesemia. (see WARNINGS).

In subjects with hepatic impairment, citalopram clearance was decreased and plasma concentrations were increased. The use of Celexa in hepatically impaired patients should be approached with caution and a lower maximum dosage is recommended (see DOSAGE AND ADMINISTRATION).

Because citalopram is extensively metabolized, excretion of unchanged drug in urine is a minor route of elimination. Until adequate numbers of patients with severe renal impairment have been evaluated during chronic treatment with Celexa, however, it should be used with caution in such patients (see DOSAGE AND ADMINISTRATION).

Information for Patients

Physicians are advised to discuss the following issues with patients for whom they prescribe Celexa.

Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of Celexa and triptans, tramadol or other serotonergic agents.

Patients should be advised that taking Celexa 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.

Although in controlled studies Celexa has not been shown to impair psychomotor performance, any psychoactive drug may impair judgment, thinking, or motor skills, so patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Celexa therapy does not affect their ability to engage in such activities.

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

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.

Patients should be cautioned about the concomitant use of Celexa 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.

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy.

Patients should be advised to notify their physician if they are breastfeeding an infant.

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

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Celexa and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for Celexa. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Celexa.

Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

Laboratory Tests

There are no specific laboratory tests recommended.

Drug Interactions

Serotonergic Drugs: See CONTRAINDICATIONS, WARNINGS, and DOSAGE AND ADMINISTRATION.

Triptans: There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of Celexa with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see WARNINGS - Serotonin Syndrome).

CNS Drugs - Given the primary CNS effects of citalopram, caution should be used when it is taken in combination with other centrally acting drugs.

Alcohol - Although citalopram did not potentiate the cognitive and motor effects of alcohol in a clinical trial, as with other psychotropic medications, the use of alcohol by depressed patients taking Celexa is not recommended.

Monoamine Oxidase Inhibitors (MAOIs) - See CONTRAINDICATIONS, WARNINGS and DOSAGE AND ADMINISTRATION.

Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) - 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 Celexa is initiated or discontinued.

Cimetidine - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%, respectively.

Celexa 20 mg/day is the maximum recommended dose for patients taking concomitant cimetidine because of the risk of QT prolongation (see WARNINGS and DOSAGE AND ADMINISTRATION).

Digoxin - In subjects who had received 21 days of 40 mg/day Celexa, combined administration of Celexa and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.

Lithium - Coadministration of Celexa (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 citalopram, caution should be exercised when Celexa and lithium are coadministered.

Pimozide - In a controlled study, a single dose of pimozide 2 mg co-administered with citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known.

Theophylline - Combined administration of Celexa (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated.

Sumatriptan - There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of a SSRI and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram) is clinically warranted, appropriate observation of the patient is advised.

Warfarin - Administration of 40 mg/day Celexa for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown.

Carbamazepine - Combined administration of Celexa (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 citalopram should be considered if the two drugs are coadministered.

Triazolam - Combined administration of Celexa (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.

Ketoconazole - Combined administration of Celexa (40 mg) and ketoconazole (200 mg) decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.

CYP2C19 Inhibitors - Celexa 20 mg/day is the maximum recommended dose for patients taking concomitant CYP2C19 inhibitors because of the risk of QT prolongation (see WARNINGS, DOSAGE AND ADMINISTRATION, AND CLINICAL PHARMACOLOGY).

Metoprolol - Administration of 40 mg/day Celexa for 22 days resulted in a two-fold increase in the plasma levels of the beta-adrenergic blocker metoprolol. Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of Celexa and metoprolol had no clinically significant effects on blood pressure or heart rate.

Imipramine and Other Tricyclic Antidepressants (TCAs) - In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.

Electroconvulsive Therapy (ECT) - There are no clinical studies of the combined use of electroconvulsive therapy (ECT) and Celexa.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Citalopram was administered in the diet to NMRI/BOM strain mice and COBS WI strain rats for 18 and 24 months, respectively. There was no evidence for carcinogenicity of citalopram in mice receiving up to 240 mg/kg/day, which is equivalent to 20 times the maximum recommended human daily dose (MRHD) of 60 mg on a surface area (mg/m2) basis. There was an increased incidence of small intestine carcinoma in rats receiving 8 or 24 mg/kg/day, doses which are approximately 1.3 and 4 times the MRHD, respectively, on a mg/m2 basis. A no-effect dose for this finding was not established. The relevance of these findings to humans is unknown.

Citalopram was mutagenic in the in vitro bacterial reverse mutation assay (Ames test) in 2 of 5 bacterial strains (Salmonella TA98 and TA1537) in the absence of metabolic activation. It was clastogenic in the in vitro Chinese hamster lung cell assay for chromosomal aberrations in the presence and absence of metabolic activation. Citalopram was not mutagenic in the in vitro mammalian forward gene mutation assay (HPRT) in mouse lymphoma cells or in a coupled in vitro/in vivo unscheduled DNA synthesis (UDS) assay in rat liver. It was not clastogenic in the in vitro chromosomal aberration assay in human lymphocytes or in two in vivo mouse micronucleus assays.

When citalopram was administered orally to 16 male and 24 female rats prior to and throughout mating and gestation at doses of 32, 48, and 72 mg/kg/day, mating was decreased at all doses, and fertility was decreased at doses ≥ 32 mg/kg/day, approximately 5 times the MRHD of 60 mg/day on a body surface area (mg/m2) basis. Gestation duration was increased at 48 mg/kg/day, approximately 8 times the MRHD.

Pregnancy

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 MRHD of 60 mg/day on a body surface area (mg/m2) basis. This dose was also associated with maternal toxicity (clinical signs, decreased body weight gain). The developmental, no-effect dose of 56 mg/kg/day is approximately 9 times the MRHD on a mg/m2 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 a mg/m2 basis. Thus, teratogenic effects were observed at a maternally toxic dose in the rat and were not observed in the rabbit.

When female rats were treated with 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 on a mg/m2 basis. The no-effect dose of 12.8 mg/kg/day is approximately 2 times the MRHD on a mg/m2 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/m2 basis. A no-effect dose was not determined in that study.

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 (see WARNINGS: Serotonin Syndrome).

Infants exposed to SSRIs in pregnancy 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. Several recent epidemiologic studies suggest a positive statistical association between SSRI use (including Celexa) in pregnancy and PPHN. Other studies do not show a significant statistical association.

Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission. Women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy.

When treating a pregnant woman with Celexa, the physician should carefully consider both the potential risks of taking an SSRI, along with the established benefits of treating depression with an antidepressant. This decision can only be made on a case by case basis (see DOSAGE AND ADMINISTRATION).

Labor and Delivery

The effect of Celexa on labor and delivery in humans is unknown.

Nursing Mothers

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.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOXED WARNING and WARNINGSClinical Worsening and Suicide Risk). Two placebo-controlled trials in 407 pediatric patients with MDD have been conducted with Celexa, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of Celexa in a child or adolescent must balance the potential risks with the clinical need.

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 Celexa.

Geriatric Use

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 (see DOSAGE AND ADMINISTRATION).

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 (see PRECAUTIONS, Hyponatremia).

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).

20 mg/day is the maximum recommended dose for patients who are greater than 60 years of age (see WARNINGS and DOSAGE AND ADMINISTRATION).

NDC 0456-4010-01

Celexa® citalopram HBr

Tablets-10 mg

Equivalent to 10 mg citalopram

100 Tablets

AllerganTM

NDC 0456-4040-01

Celexa® citalopram HBr

Tablets-40 mg

Equivalent to 40 mg citalopram

100 Tablets

AllerganTM

Get emergency medical help if you have signs of an allergic reaction to Celexa: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

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.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;

• blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;

• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;

• severe nervous system reaction - very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;

• high levels of serotonin in the body - agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting; or

• low levels of sodium in the body - headache, confusion, slurred speech, severe weakness, vomiting, feeling unsteady.

Common Celexa side effects may include:

• problems with memory or concentration;

• headache, drowsiness;

• dry mouth, increased sweating;

• numbness or tingling;

• increased appetite, nausea, diarrhea, gas;

• fast heartbeats, feeling shaky;

• sleep problems (insomnia), feeling tired;

• cold symptoms such as stuffy nose, sneezing, sore throat;

• changes in weight; or

• difficulty having an orgasm.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to citalopram: oral solution, oral tablet

Along with its needed effects, citalopram (the active ingredient contained in Celexa) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking citalopram:

• Agitation
• blurred vision
• confusion
• fever
• increase in the frequency of urination or amount of urine produced
• lack of emotion
• loss of memory
• menstrual changes
• skin rash or itching
• trouble breathing

• Behavior change similar to drunkenness
• bleeding gums
• breast tenderness or enlargement or unusual secretion of milk (in females)
• chills
• convulsions (seizures)
• diarrhea
• difficulty with concentrating
• dizziness or fainting
• drowsiness
• increased hunger
• increased thirst
• irregular heartbeat
• lack of energy
• lethargy
• nosebleed
• overactive reflexes
• painful urination
• poor coordination
• purple or red spots on the skin
• rapid weight gain
• red or irritated eyes
• redness, tenderness, itching, burning, or peeling of the skin
• shivering
• slow or irregular heartbeat (less than 50 beats per minute)
• sore throat
• stupor
• sweating
• swelling of the face, ankles, or hands
• talking or acting with excitement you cannot control
• trembling, shaking, or twitching
• trouble with holding or releasing urine
• unusual or sudden body or facial movements or postures
• unusual tiredness or weakness

• Abdominal or stomach pain
• back or leg pains
• black, tarry stools
• bloating
• bloody stools
• chest pain
• confusion as to time, place, or person
• constipation
• cough
• darkened urine
• difficult or fast breathing
• difficulty with swallowing
• drooling
• fast, slow, or irregular heartbeat
• general body swelling
• hive-like swelling on the face, eyelids, lips, tongue, or throat
• hives
• holding false beliefs that cannot be changed by fact
• impaired consciousness, ranging from confusion to coma
• indigestion
• itching, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• loss of appetite
• loss of bladder control
• loss of consciousness
• muscle cramps or spasms
• muscle tightness
• muscle twitching or jerking
• painful or prolonged erection of the penis
• pale skin
• penile erections, frequent or continuing
• recurrent fainting
• rhythmic movement of the muscles
• seeing, hearing, or feeling things that are not there
• swelling of the breasts or unusual milk production
• tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area
• tightness in the chest
• total body jerking
• twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• uncontrolled jerking or twisting movements
• unusual excitement
• vomiting of blood or material that looks like coffee grounds
• yellowing of the eyes or skin

Some side effects of citalopram may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decrease in sexual desire or ability
• sleepiness or unusual drowsiness

• Body aches or pain
• change in sense of taste
• gas
• headache (severe and throbbing)
• heartburn
• increased sweating
• increased yawning
• loss of voice
• pain in the muscles or joints
• sneezing
• stuffy or runny nose
• tingling, burning, or prickly feelings on the skin
• tooth grinding
• unusual increase or decrease in weight
• watering of the mouth

• Bruising
• inability to sit still
• large, flat, blue or purplish patches in the skin
• need to keep moving
• uncontrolled eye movements

• May be used in the treatment of moderate-to-severe depression (Major Depressive Disorder).
• Less likely to cause drowsiness than some other antidepressants.
• Has also been used off-label for other conditions such as anxiety, alcoholism, eating disorders, fibromyalgia, and obsessive-compulsive disorder.
• SSRIs in general, are better tolerated than many other medicines used in the treatment of depression.
• Celexa is less likely than some other SSRIs to interact with other medications.
• SSRIs in general, are better tolerated than many other medicines used in the treatment of depression.
• Celexa is available as a generic under the name citalopram.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Insomnia, dry mouth, drowsiness, nausea, increased sweating and sexual dysfunction. Side effects may be more likely with Celexa (citalopram) compared to escitalopram, another SSRI.
• May increase the risk of suicidal thoughts or behavior in young adults (similar to other antidepressants).
• Interaction or over-dosage may cause serotonin syndrome (symptoms include agitation, hallucinations, fast heart rate, dizziness, muscle tremor, nausea, vomiting, diarrhea).
• May cause a discontinuation syndrome if abruptly stopped or interrupted (symptoms include nausea, vomiting, diarrhea, headaches, sweating, tremors, vivid dreams, insomnia)
• May affect the heart and heart rhythm (for example, prolong the QT interval); more likely at dosages greater than 40mg/day.
• May not be suitable for people with preexisting cardiac disease or abnormalities or with low potassium or low magnesium levels.
• May also precipitate seizures or glaucoma in susceptible people; decrease sodium levels in the blood and affect a person's ability to concentrate or perform hazardous tasks. Avoid alcohol while taking Celexa.
• May precipitate a manic or mixed episode in people with bipolar disorder.
• May impair your judgment and affect your ability to drive or operate machinery. Alcohol should be avoided.
• May increase the risk of bleeding, especially if used with other drugs that also increase bleeding risk.
• May cause lowering of total body sodium (called hyponatremia); elderly people or people taking diuretics or already dehydrated may be more at risk.
• May interact with a number of other drugs including those metabolized by hepatic enzymes CYP 3A4 and 2C19, other antidepressants and medicines that also cause serotonin release (such as tramadol, St John's wort, and opioids).
• Rarely causes seizures.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

Celexa is an effective antidepressant but it may cause more side effects than escitalopram, a related drug.