Citalopram

Check Drug InteractionsCheck known drug interactions.

Citalopram Prescribing Information

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and
young adult patients in short- term studies. Closely monitor all antidepressant-treated
patients for clinical worsening, and for emergence of suicidal thoughts and behaviors

[see Warnings and Precautions (

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 RangeCitalopram 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.

)].

Citalopram is not approved for use in pediatric patients

[see Use in Specific Populations (

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 ]

. Decreased appetite and weight loss have been observed in association with the use of SSRIs in pediatric patients.

)].

Citalopram is indicated for the treatment of major depressive disorder (MDD) in adults

[see Clinical Studies (

14 CLINICAL STUDIES

The efficacy of Citalopram as a treatment for major depressive disorder was established in two placebo-controlled studies (of 4 to 6 weeks duration) in adult outpatients (ages 18-66) meeting DSM-III or DSM-III-R criteria for major depressive disorder (MDD) (Studies 1 and 2).

Study 1, a 6-week trial in which patients received fixed Citalopram doses of 10 mg, 20 mg, 40 mg, and 60 mg daily, showed that Citalopram 40 daily and 60 mg daily (1.5 times the maximum recommended daily dosage) was effective as measured by the Hamilton Depression Rating Scale (HAMD) total score, the primary efficacy endpoint. The HAMD-17 is a 17-item, clinician-rated scale used to assess severity of depressive symptoms. Scores on the HAMD-17 range from 0 to 52, with higher scores indicating more severe depression. This study showed no clear effect of the 10 mg and 20 mg daily doses, and the 60 mg daily dose was not more effective than the 40 mg daily dose. Due to the risk of QTc prolongation and ventricular arrhythmias, the maximum recommended dosage of Citalopram is 40 mg once daily.

In study 2, a 4-week, placebo-controlled trial in patients with MDD, the initial dose was 20 mg daily, followed by titration to the maximum tolerated dose or a maximum dose of 80 mg daily (2 times the maximum recommended daily dosage).

Patients treated with Citalopram showed statistically significantly greater improvement than placebo patients on the HAMD total score, the primary efficacy endpoint. In three additional placebo-controlled trials in patients with MDD, the difference in response to treatment between patients receiving Citalopram and patients receiving placebo was not statistically significant.

In two long-term studies, patients with MDD who had responded to Citalopram during an initial 6 or 8 weeks of acute treatment were randomized to continuation of Citalopram or placebo. In one study, patients received fixed doses of Citalopram 20 mg or 40 mg daily and in the second study, patients received flexible doses of Citalopram 20 mg daily to 60 mg daily (1.5 times the maximum recommended daily dosage). In both studies, patients receiving continued Citalopram treatment experienced statistically significantly lower relapse rates over the subsequent 6 months compared to those receiving placebo. In the fixed-dose study, the decreased rate of depression relapse was similar in patients receiving 20 mg or 40 mg daily of Citalopram. Due to the risk of QTc prolongation and ventricular arrhythmias, the maximum recommended dosage of Citalopram is 40 mg once daily.

Analyses of the relationship between treatment outcome and age, gender, and race did not suggest any differential responsiveness on the basis of these patient characteristics.

)]

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.

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 Serotonin Syndrome

SSRIs, including Citalopram, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs

[see Contraindications , Drug Interactions ]

. Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome were noted in 0.1% of MDD patients treated with Citalopram in premarketing clinical trials.

Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

The concomitant use of Citalopram with MAOIs is contraindicated. In addition, do not initiate Citalopram in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Citalopram, discontinue Citalopram before initiating treatment with the MAOI

[see Contraindications , Drug Interactions ].

Monitor all patients taking Citalopram for the emergence of serotonin syndrome. Discontinue treatment with Citalopram and any concomitant serotonergic agents immediately if the above symptoms occur and initiate supportive symptomatic treatment. If concomitant use of Citalopram with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

), Drug Interactions (

7 DRUG INTERACTIONS

Table 5 presents clinically important drug interactions with Citalopram.

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 , Contraindications , Warnings and Precautions ].
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 ].
Intervention:	Citalopram is contraindicated in patients taking pimozide [see Contraindications, Warnings and Precautions ].
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 ].
Intervention:	Avoid concomitant use of Citalopram with drugs that prolong the QT interval (Citalopram is contraindicated in patients taking pimozide) [see Contraindications , Warnings and Precautions ].
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 ].
Intervention:	The maximum recommended dosage of Citalopram is 20 mg daily when used concomitantly with a CYP2C19 inhibitor [see Dosage and Administration , Warnings and Precautions ].
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 ].
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 ].

CYP2C19 Inhibitors

: Citalopram 20 mg daily is the maximum recommended dosage for patients taking concomitant CYP2C19 inhibitors (

5.2, 7.1

)]

taking pimozide because of risk of QT prolongation

[see Drug Interactions (

7 DRUG INTERACTIONS

Table 5 presents clinically important drug interactions with Citalopram.

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 , Contraindications , Warnings and Precautions ].
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 ].
Intervention:	Citalopram is contraindicated in patients taking pimozide [see Contraindications, Warnings and Precautions ].
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 ].
Intervention:	Avoid concomitant use of Citalopram with drugs that prolong the QT interval (Citalopram is contraindicated in patients taking pimozide) [see Contraindications , Warnings and Precautions ].
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 ].
Intervention:	The maximum recommended dosage of Citalopram is 20 mg daily when used concomitantly with a CYP2C19 inhibitor [see Dosage and Administration , Warnings and Precautions ].
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 ].
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 ].

CYP2C19 Inhibitors

: Citalopram 20 mg daily is the maximum recommended dosage for patients taking concomitant CYP2C19 inhibitors (

5.2, 7.1

)]

with known hypersensitivity to citalopram or any of the inactive ingredients in Citalopram. Reactions have included angioedema and anaphylaxis
[see Adverse Reactions (
6.2 Post marketing Experience
The following adverse reactions have been identified during postapproval use of citalopram, the racemate, or escitalopram, the S-enantiomer of citalopram. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders
: hemolytic anemia, thrombocytopenia, prothrombin decreased.
Cardiac Disorders
: torsade de pointes, ventricular arrhythmia, QT prolonged
Endocrine Disorders
: hyperprolactinemia
Eye Disorders
: angle-closure glaucoma
Gastrointestinal Disorders
: gastrointestinal hemorrhage, pancreatitis
General Disorders and Administrative Site Conditions
: withdrawal syndrome
Hepatobiliary Disorders
: hepatic necrosis
Immune System Disorders
: anaphylaxis, allergic reaction
Musculoskeletal and Connective Tissue Disorders
: rhabdomyolysis
Nervous System Disorders
: grand mal convulsion(s), myoclonus, choreoathetosis, dyskinesia, akathisia, nystagmus
Pregnancy, Puerperium and Perinatal Conditions
: spontaneous abortion
Psychiatric Disorders
: delirium
Renal and Urinary Disorders
: acute renal failure
Reproductive System and Breast Disorders
: priapism
Respiratory, Thoracic and Mediastinal Disorders:
anosmia, hyposmia
Skin and Subcutaneous Tissue Disorders:
Stevens Johnson Syndrome, epidermal necrolysis, angioedema, erythema multiforme, ecchymosis
Vascular Disorders:
thrombosis
)]
.

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Hypersensitivity reactions
[see Contraindications (
4 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 , Drug Interactions ]
.
taking pimozide because of risk of QT prolongation
[see Drug Interactions ]
.
with known hypersensitivity to citalopram or any of the inactive ingredients in Citalopram. Reactions have included angioedema and anaphylaxis
[see Adverse Reactions ]
.
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
).
)]

Suicidal thoughts and behaviors in adolescents and young adults

[see Warnings and Precautions (

5.1 Suicidal Thoughts and Behavior in Adolescents and Young Adults

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 RangeCitalopram 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

)]

QT-prolongation and torsade de pointes
[see Warnings and Precautions (
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 , Clinical Pharmacology ]
.
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 ]
. 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 , Drug Interactions , Use in Specific Populations , Clinical Pharmacology ]
.
Electrolyte and/or ECG monitoring is recommended in certain circumstances. Patients being considered for treatment with Citalopram who are at risk for significant electrolyte disturbances should have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia (and/or hypomagnesemia) may increase the risk of QTc prolongation and arrhythmia and should be corrected prior to initiation of treatment and periodically monitored. ECG monitoring is recommended in patients for whom Citalopram use is not recommended unless the benefits clearly outweigh the risks for a particular patient (see above). These include those patients with the cardiac conditions noted above, and those taking other drugs that may prolong the QTc interval.
Discontinue Citalopram in patients who are found to have persistent QTc measurements >500 ms. If patients taking Citalopram experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, orsyncope, the prescriber should initiate further evaluation, including cardiac monitoring.
)]
Serotonin syndrome
[see Warnings and Precautions (
5.3 Serotonin Syndrome
SSRIs, including Citalopram, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs
[see Contraindications , Drug Interactions ]
. Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome were noted in 0.1% of MDD patients treated with Citalopram in premarketing clinical trials.
Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
The concomitant use of Citalopram with MAOIs is contraindicated. In addition, do not initiate Citalopram in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Citalopram, discontinue Citalopram before initiating treatment with the MAOI
[see Contraindications , Drug Interactions ].
Monitor all patients taking Citalopram for the emergence of serotonin syndrome. Discontinue treatment with Citalopram and any concomitant serotonergic agents immediately if the above symptoms occur and initiate supportive symptomatic treatment. If concomitant use of Citalopram with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
)]
Increased risk of bleeding
[see Warnings and Precautions (
5.4 Increased Risk of Bleeding
Drugs that interfere with serotonin reuptake inhibition, including Citalopram, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this 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.
Based on data from the 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 Use in Specific Populations ].
Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.
Inform patients about the increased risk of bleeding associated with the concomitant use of Citalopram and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio
[see Drug Interactions ]
.
)]
Activation of mania or hypomania
[see Warnings and Precautions (
5.5 Activation of Mania or Hypomania
In patients with bipolar disorder, treating a depressive episode with Citalopram or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania or hypomania were reported in 0.1% of undiagnosed patients treated with Citalopram. Prior to initiating treatment with Citalopram, screen patients for any personal or family history of bipolar disorder, mania, or hypomania
[see Dosage and Administration ]
.
)]
Discontinuation syndrome
[see Warnings and Precautions (
5.6 Discontinuation Syndrome
Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible
[see Dosage and Administration ]
.
)]
Seizures
[see Warnings and Precautions (
5.7 Seizures
Citalopram has not been systematically evaluated in patients with seizure disorders. Patients with a history of seizures were excluded from clinical studies. In clinical trials of Citalopram, seizures occurred in 0.3% of patients treated with Citalopram (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). Citalopram should be prescribed with caution in patients with a seizure disorder.
)]
Angle-closure glaucoma
[see Warnings and Precautions (
5.8 Angle-closure Glaucoma
The pupillary dilation that occurs following use of many antidepressant drugs, including Citalopram, may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including Citalopram, in patients with untreated anatomically narrow angles.
)]
Hyponatremia
[see Warnings and Precautions (
5.9 Hyponatremia
Hyponatremia may occur as a result of treatment with SSRIs, including Citalopram. Cases of serum sodium lower than 110 mmol/L have been reported. 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. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
In patients with symptomatic hyponatremia, discontinue Citalopram and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs
[see Use in Specific Populations ]
.
)]
Sexual Dysfunction
[see Warnings and Precautions (
5.10 Sexual Dysfunction
Use of SSRIs, including Citalopram, may cause symptoms of sexual dysfunction [
see Adverse Reactions ]
. In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm.
It is important for prescribers to inquire about sexual function prior to initiation of Citalopram and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.
)]

Table 5 presents clinically important drug interactions with Citalopram.

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 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 and Warnings and Precautions ]. ), Contraindications ( 4 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 , Drug Interactions ] . taking pimozide because of risk of QT prolongation [see Drug Interactions ] . with known hypersensitivity to citalopram or any of the inactive ingredients in Citalopram. Reactions have included angioedema and anaphylaxis [see Adverse Reactions ] . 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 ( 5.3 Serotonin Syndrome SSRIs, including Citalopram, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications , Drug Interactions ] . Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome were noted in 0.1% of MDD patients treated with Citalopram in premarketing clinical trials. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of Citalopram with MAOIs is contraindicated. In addition, do not initiate Citalopram in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Citalopram, discontinue Citalopram before initiating treatment with the MAOI [see Contraindications , Drug Interactions ]. Monitor all patients taking Citalopram for the emergence of serotonin syndrome. Discontinue treatment with Citalopram and any concomitant serotonergic agents immediately if the above symptoms occur and initiate supportive symptomatic treatment. If concomitant use of Citalopram with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. )].
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 Pharmacodynamics In vitro and in vivo studies in animals suggest that citalopram is a selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake. 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. Cardiac Electrophysiology Individually corrected QTc (QTcNi) interval was evaluated in a randomized, placebo and active (moxifloxacin 400 mg) controlled cross-over, escalating multiple-dose study in 119 healthy subjects. The maximum mean (upper bound of the 95% one-sided confidence interval) difference from placebo were 8.5 (10.8) and 18.5 (21.0) msec for 20 mg and 60 mg (1.5 times the maxium recommended dosage) citalopram, respectively. Based on the established exposure-response relationship, the predicted QTcNi change from placebo (upper bound of the 95% one-sided confidence interval) under the C_maxfor the dose of 40 mg is 12.6 (14.3) msec [see Warnings and Precautions ] . )].
Intervention:	Citalopram is contraindicated in patients taking pimozide [see Contraindications( 4 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 , Drug Interactions ] . taking pimozide because of risk of QT prolongation [see Drug Interactions ] . with known hypersensitivity to citalopram or any of the inactive ingredients in Citalopram. Reactions have included angioedema and anaphylaxis [see Adverse Reactions ] . 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 ( 5.2 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 , Clinical Pharmacology ] . 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 ] . 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 , Drug Interactions , Use in Specific Populations , Clinical Pharmacology ] . Electrolyte and/or ECG monitoring is recommended in certain circumstances. Patients being considered for treatment with Citalopram who are at risk for significant electrolyte disturbances should have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia (and/or hypomagnesemia) may increase the risk of QTc prolongation and arrhythmia and should be corrected prior to initiation of treatment and periodically monitored. ECG monitoring is recommended in patients for whom Citalopram use is not recommended unless the benefits clearly outweigh the risks for a particular patient (see above). These include those patients with the cardiac conditions noted above, and those taking other drugs that may prolong the QTc interval. Discontinue Citalopram in patients who are found to have persistent QTc measurements >500 ms. If patients taking Citalopram experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, orsyncope, the prescriber should initiate further evaluation, including cardiac monitoring. )].
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 Pharmacodynamics In vitro and in vivo studies in animals suggest that citalopram is a selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake. 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. Cardiac Electrophysiology Individually corrected QTc (QTcNi) interval was evaluated in a randomized, placebo and active (moxifloxacin 400 mg) controlled cross-over, escalating multiple-dose study in 119 healthy subjects. The maximum mean (upper bound of the 95% one-sided confidence interval) difference from placebo were 8.5 (10.8) and 18.5 (21.0) msec for 20 mg and 60 mg (1.5 times the maxium recommended dosage) citalopram, respectively. Based on the established exposure-response relationship, the predicted QTcNi change from placebo (upper bound of the 95% one-sided confidence interval) under the C_maxfor the dose of 40 mg is 12.6 (14.3) msec [see Warnings and Precautions ] . )].
Intervention:	Avoid concomitant use of Citalopram with drugs that prolong the QT interval (Citalopram is contraindicated in patients taking pimozide) [see Contraindications ( 4 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 , Drug Interactions ] . taking pimozide because of risk of QT prolongation [see Drug Interactions ] . with known hypersensitivity to citalopram or any of the inactive ingredients in Citalopram. Reactions have included angioedema and anaphylaxis [see Adverse Reactions ] . 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 ( 5.2 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 , Clinical Pharmacology ] . 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 ] . 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 , Drug Interactions , Use in Specific Populations , Clinical Pharmacology ] . Electrolyte and/or ECG monitoring is recommended in certain circumstances. Patients being considered for treatment with Citalopram who are at risk for significant electrolyte disturbances should have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia (and/or hypomagnesemia) may increase the risk of QTc prolongation and arrhythmia and should be corrected prior to initiation of treatment and periodically monitored. ECG monitoring is recommended in patients for whom Citalopram use is not recommended unless the benefits clearly outweigh the risks for a particular patient (see above). These include those patients with the cardiac conditions noted above, and those taking other drugs that may prolong the QTc interval. Discontinue Citalopram in patients who are found to have persistent QTc measurements >500 ms. If patients taking Citalopram experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, orsyncope, the prescriber should initiate further evaluation, including cardiac monitoring. )].
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 Pharmacodynamics In vitro and in vivo studies in animals suggest that citalopram is a selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake. 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. Cardiac Electrophysiology Individually corrected QTc (QTcNi) interval was evaluated in a randomized, placebo and active (moxifloxacin 400 mg) controlled cross-over, escalating multiple-dose study in 119 healthy subjects. The maximum mean (upper bound of the 95% one-sided confidence interval) difference from placebo were 8.5 (10.8) and 18.5 (21.0) msec for 20 mg and 60 mg (1.5 times the maxium recommended dosage) citalopram, respectively. Based on the established exposure-response relationship, the predicted QTcNi change from placebo (upper bound of the 95% one-sided confidence interval) under the C_maxfor the dose of 40 mg is 12.6 (14.3) msec [see Warnings and Precautions ] . )].
Intervention:	The maximum recommended dosage of Citalopram is 20 mg daily when used concomitantly with a CYP2C19 inhibitor [see Dosage and Administration ( 2.4 Dosage Modifications with Concomitant Use of CYP2C19 Inhibitors The Maximum recommended dosage of Citalopram when used concomitantly with a CYP2C19 inhibitor is 20 mg once daily [see Warnings and Precautions ( 5.2), Drug Interactions ]. ), Warnings and Precautions ( 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 , Clinical Pharmacology ] . 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 ] . 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 , Drug Interactions , Use in Specific Populations , Clinical Pharmacology ] . Electrolyte and/or ECG monitoring is recommended in certain circumstances. Patients being considered for treatment with Citalopram who are at risk for significant electrolyte disturbances should have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia (and/or hypomagnesemia) may increase the risk of QTc prolongation and arrhythmia and should be corrected prior to initiation of treatment and periodically monitored. ECG monitoring is recommended in patients for whom Citalopram use is not recommended unless the benefits clearly outweigh the risks for a particular patient (see above). These include those patients with the cardiac conditions noted above, and those taking other drugs that may prolong the QTc interval. Discontinue Citalopram in patients who are found to have persistent QTc measurements >500 ms. If patients taking Citalopram experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, orsyncope, the prescriber should initiate further evaluation, including cardiac monitoring. )].
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 Serotonin Syndrome SSRIs, including Citalopram, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications , Drug Interactions ] . Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome were noted in 0.1% of MDD patients treated with Citalopram in premarketing clinical trials. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of Citalopram with MAOIs is contraindicated. In addition, do not initiate Citalopram in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Citalopram, discontinue Citalopram before initiating treatment with the MAOI [see Contraindications , Drug Interactions ]. Monitor all patients taking Citalopram for the emergence of serotonin syndrome. Discontinue treatment with Citalopram and any concomitant serotonergic agents immediately if the above symptoms occur and initiate supportive symptomatic treatment. If concomitant use of Citalopram with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. )].
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 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including Citalopram, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this 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. Based on data from the 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 Use in Specific Populations ]. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the increased risk of bleeding associated with the concomitant use of Citalopram and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Drug Interactions ] . )].

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