Citalopram

Pronunciation

Pronunciation: sye-TAL-oh-pram
Class: SSRI

Trade Names

Celexa
- Tablets, oral 10 mg
- Tablets, oral 20 mg
- Tablets, oral 40 mg

Citalopram
- Solution, oral 2 mg/mL

Apo-Citalopram (Canada)
CO Citalopram (Canada)
Gen-Citalopram (Canada)
PMS-Citalopram (Canada)
RAN-Citalopram (Canada)
ratio-Citalopram (Canada)
Sandoz Citalopram (Canada)

Pharmacology

Inhibits the CNS neuronal uptake of serotonin, potentiating serotonergic activity.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

T max is approximately 4 h. Approximately 80% bioavailable; absorption is not affected by food. Steady state is reached in approximately 1 wk.

Distribution

Vd is approximately 12 L/kg. Approximately 80% bound to plasma proteins.

Metabolism

Metabolized in the liver; CYP3A4 and CYP2C19 are the primary isozymes involved in N-demethylation of citalopram. Metabolites are demethylcitalopram, didemethylcitalopram, citalopram-N-oxide, and deaminated propionic acid derivative; metabolites do not appear to contribute to antidepressant actions.

Elimination

Approximately 10% is excreted in urine as citalopram. Systemic Cl is 330 mL/min (approximately 20% is because of renal Cl). The half-life is approximately 35 h.

Special Populations

Renal Function Impairment

Oral Cl decreased 17% in mild to moderate renal impairment.

Hepatic Function Impairment

Oral Cl decreased 37% and half-life doubled in reduced hepatic function.

Elderly
Multiple dose

AUC increased 23% and half-life increased 30%.

Single dose

AUC increased 30% and half-life increased 50%.

Gender

AUC in women was 1.5 to 2 times that in men in 3 studies; no difference was observed in 5 other studies.

Indications and Usage

Treatment of depression.

Unlabeled Uses

Alcoholism; binge-eating disorder; diabetic neuropathy; generalized anxiety disorder; impulsive aggressive behavior; irritable bowel syndrome; obsessive-compulsive disorder; panic disorder; pathological gambling; posttraumatic stress disorder; premenstrual disorders; stuttering.

Contraindications

Concomitant use of MAOIs or pimozide; hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO Initiate with 20 mg once daily and titrate up to a max dosage of 40 mg/day; dose increases should occur at intervals of no less than 1 wk. If bothersome adverse reactions occur, consider a decrease in dosage to 20 mg once daily.

CYP2C19

PO 20 mg once daily is the max recommended dose in patients who are CYP2C19 poor metabolizers or patients taking CYP2C19 inhibitors (eg, cimetidine).

Elderly

PO 20 mg once daily is the maximum recommended dose for patients who are older than 60 y.

Hepatic Function Impairment

PO 20 mg/day (max).

General Advice

  • Administer dose once daily, in the morning or evening, without regard to meals. Administer with food if GI upset occurs.
  • Use dosing syringe, dosing spoon, or dosing cup to measure and administer prescribed dose of oral solution.
  • When discontinuation of therapy is necessary, a gradual reduction in dose rather than abrupt cessation is recommended whenever possible.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Alcohol

May potentiate the effects of alcohol; use of alcohol is not advised.

Antiparkinson agents (ie, rasagiline, selegiline), metoclopramide, nefazodone, opioid analgesics (eg, fentanyl), other SSRIs (eg, fluoxetine), sibutramine, SNRIs (eg, venlafaxine), St. John's wort, tryptophan

The risk of serotonin syndrome may be increased. Closely monitor patients.

Aspirin, NSAIDs (eg, ibuprofen), warfarin

Risk of bleeding (eg, GI bleeding) may be increased. Use with caution and carefully monitor the patient.

Beta-blockers (eg, metoprolol, propranolol)

Inhibition of beta-blocker's metabolism may occur, resulting in excessive beta blockade (eg, bradycardia). Coadministration of metoprolol with citalopram has increased plasma levels of metoprolol 2-fold.

Carbamazepine

The Cl of citalopram may be increased, decreasing serum concentrations.

Charcoal

Charcoal can reduce absorption of citalopram, resulting in decreased efficacy.

Cimetidine

Serum levels of citalopram may be increased. Because of the risk of QT prolongation, the dosage of citalopram should not exceed 20 mg/day in patients receiving cimetidine.

Clozapine

Serum clozapine levels may be elevated, resulting in increased pharmacologic and toxic effects. Monitor closely. Clozapine dosage adjustments may be needed when adding or stopping citalopram.

CNS drugs (eg, amphetamines, methylphenidate)

Use citalopram with caution in patients receiving CNS drugs.

CYP2C19 inhibitors (eg, omeprazole)

Plasma concentrations and toxic effects of citalopram may be increased by coadministration of a CYP2C19 inhibitor. Because of the risk of QT prolongation, the dosage of citalopram should not exceed 20 mg/day in patients receiving CYP2C19 inhibitors.

Cyproheptadine

May decrease the pharmacologic effect of citalopram.

Drugs that may prolong the QT interval (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol], arsenic trioxide, chlorpromazine, cisapride, dolasetron, droperidol, halofantrine, mefloquine, mesoridazine, moxifloxacin, nilotinib, ondansetron, pentamidine, pimozide, tacrolimus, thioridazine, vandetanib, ziprasidone)

Coadministration may increase the risk of prolonged QT interval with possible development of cardiac arrhythmias, including torsades de pointes.

Ketoconazole

Ketoconazole plasma levels may be reduced slightly.

Linezolid

If coadministration cannot be avoided, closely observe the patient for signs and symptoms of serotonin syndrome (eg, cognitive dysfunction, hyperpyrexia, hyperreflexia, incoordination). If signs or symptoms occur, consider discontinuing one or both agents.

Lithium

Lithium may enhance the serotonergic effects of citalopram; use caution if coadministered. Monitor lithium levels following initiation of citalopram and adjust the lithium dose as necessary.

MAOIs (eg, phenelzine)

Coadministration is contraindicated. Allow at least 14 days to elapse between discontinuing an MAOI and starting citalopram. Similarly, allow at least 14 days after stopping citalopram before starting an MAOI.

Methylene blue

Risk of neurologic adverse reactions, including serotonin syndrome, may be increased. Avoid concurrent use.

Pimozide

Coadministration may increase the risk of prolonged QT interval with possible development of cardiac arrhythmias, including torsades de pointes. Concurrent use is contraindicated.

Serotonin 5-HT 1 receptor agonists (eg, almotriptan, sumatriptan)

There have been rare postmarketing reports of serotonin syndrome following coadministration.

Tramadol

Serotonin syndrome, including CNS irritability, shivering, and myoclonus, may occur in some patients. There is also an increased risk of seizures.

Trazodone

Unexpected adverse effects, including the potential for development of serotonin syndrome, may occur when trazodone and citalopram are coadministered. Monitor closely.

Tricyclic antidepressants (eg, desipramine, imipramine)

The concentration of the imipramine metabolite desipramine was increased 50% with concurrent use. Use with caution.

Adverse Reactions

Cardiovascular

Hypotension, postural hypotension, tachycardia (at least 1%); QT prolongation, torsades de pointes, ventricular arrhythmia (postmarketing).

CNS

Somnolence (18%); insomnia (15%); tremor (8%); fatigue (5%); anxiety, decreased libido (4%); agitation (3%); yawning (2%); aggravated depression, amnesia, apathy, confusion, depression, impaired concentration, increased appetite, migraine, paresthesia, suicide attempts (at least 1%); akathisia, choreoathetosis, delirium, dyskinesia, nystagmus, tonic-clonic seizures, withdrawal syndrome (postmarketing).

Dermatologic

Increased sweating (11%); pruritus, rash (at least 1%); epidermal necrolysis, erythema multiforme (postmarketing).

EENT

Abnormal accommodation (at least 1%); glaucoma (postmarketing).

GI

Nausea (21%); dry mouth (20%); diarrhea (8%); dyspepsia (5%); anorexia, vomiting (4%); abdominal pain (3%); flatulence, increased saliva, taste perversion (at least 1%); GI hemorrhage, pancreatitis (postmarketing).

Genitourinary

Ejaculation disorder (6%); dysmenorrhea, impotence (3%); amenorrhea, polyuria (at least 1%); anorgasmia (1%); acute renal failure, priapism, prolactinemia, spontaneous abortion (postmarketing).

Hematologic-Lymphatic

Ecchymosis, hemolytic anemia, thrombocytopenia, thrombosis (postmarketing).

Hepatic

Hepatic necrosis (postmarketing).

Lab Tests

Decreased prothrombin (postmarketing).

Metabolic-Nutritional

Decreased or increased weight (at least 1%).

Musculoskeletal

Arthralgia, myalgia (2%); myoclonus, rhabdomyolysis (postmarketing).

Respiratory

Rhinitis, upper respiratory tract infection (5%); sinusitis (3%); coughing (at least 1%).

Miscellaneous

Fever (2%); allergic reaction, anaphylaxis, angioedema, chest pain (postmarketing).

Precautions

Warnings

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. When considering the use of any antidepressant in a child, adolescent, or young adult, balance this risk with clinical need. Appropriately monitor and closely observe patients of all ages for clinical worsening, suicidality, or unusual changes in behavior during the initial few months of therapy or at times of increases or decreases in dose. Advise families and caregivers of the need for close observation and communication with the health care provider.


Monitor

Monitor patients for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy or at times of increases or decreases in dose. Frequently assess patients for response to treatment. Periodically review therapy to determine if therapy needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated. Monitor potassium and magnesium prior to initiation and periodically during therapy in patients at risk of significant electrolyte disturbances. Monitor ECG in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute MI, or uncompensated heart failure, or those on concomitant therapy that prolongs the QT interval. Monitor patients for the emergence of serotonin syndrome or NMS-like signs and symptoms.


Pregnancy

Category C . Neonates exposed to citalopram late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding, and may have an increased risk of persistent pulmonary hypertension of the newborn. Consider potential risks and benefits of treatment when treating women during the third trimester.

Lactation

Excreted in breast milk; may adversely affect infants.

Children

Safety and efficacy not established.

Elderly

Lower maximum doses are recommended. Elderly patients may be at greater risk of hyponatremia.

Renal Function

Use with caution in patients with severe renal impairment (CrCl less than 20 mL/min).

Hepatic Function

Use with caution; a lower max dose is recommended.

Hazardous Tasks

May impair judgment, thinking, or motor skills.

Abnormal bleeding

Bleeding episodes have occurred in patients treated with psychotropic drugs that interfere with serotonin reuptake.

Activation of mania/hypomania

Has been reported. Use cautiously in patients with history of mania/hypomania.

Discontinuation of treatment

Withdrawal symptoms have been reported following rapid discontinuation of therapy. If treatment is to be discontinued or the dose reduced, gradually taper the dose and monitor the patient for withdrawal symptoms (eg, abnormal skin sensations, agitation, anxiety, confusion, dizziness, dysphoric mood, emotional lability, headaches, hypomania, insomnia, irritability, lethargy). If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after the patient has stabilized.

Hyponatremia

Hyponatremia and/or SIADH may occur. Use with caution in elderly patients, volume-depleted patients, or those taking diuretics.

QT prolongation

Dose-dependent QT prolongation has occurred; dosage should not exceed 40 mg/day (20 mg/day in CYP2C19 poor metabolizers or patients taking concomitant CYP2C19 inhibitors [eg, cimetidine], patients with hepatic impairment, or patients older than 60 y). Avoid use in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute MI, uncompensated heart failure, or in patients taking other drugs known to prolong the QTc interval. Correct hypokalemia and hypomagnesemia prior to initiation of treatment. Discontinue treatment in patients who have persistent QTc measurements more than 500 msec.

Screening for bipolar disorder

Screen patients with depression for risk of bipolar disorder prior to initiating therapy with an antidepressant.

Seizures

May occur; use with caution in patients with a history of seizures.

Serotonin syndrome or NMS-like reactions

Life-threatening serotonin syndrome or NMS-like reactions may occur, particularly with coadministration of serotonergic drugs.

Overdosage

Symptoms

Acute renal failure, amnesia, coma, confusion, cyanosis, dizziness, ECG changes (including QT prolongation, nodal rhythm, ventricular arrhythmia, torsades de pointes), hyperventilation, nausea, rhabdomyolysis, seizures, sinus tachycardia, somnolence, sweating, tremor, vomiting.

Patient Information

  • Advise patients or caregivers to read the Medication Guide before starting therapy and each time the medication is refilled.
  • Advise patients that dose will usually be started low and then increased until max benefit is obtained.
  • Instruct patients to take prescribed dose once daily in the morning or evening without regard to meals, but to take with food if stomach upset occurs.
  • Advise patients or caregivers using oral solution to measure and administer prescribed dose using dosing syringe, dosing spoon, or dosing cup.
  • Advise patients that if a dose is missed, to take it as soon as possible and then return to the normal schedule. However, if it is almost time for the next dose, advise them to skip the missed dose and take the next dose at the regularly scheduled time. Instruct patients that if a dose is skipped to not double the dose to catch up.
  • Instruct patients to not change the dose or stop taking unless advised by their health care provider.
  • Advise patients or caregivers that it may take between 1 and 4 wk of therapy before improvement is noted and to not stop taking the medication when they feel better.
  • Caution patients to not take aspirin or aspirin-containing products, NSAIDs, ginkgo biloba, or any other medication or herbal product that can affect coagulation, unless advised by their health care provider, because of increased risk of serious bleeding.
  • Instruct patients to contact their health care provider if symptoms do not appear to be getting better or they worsen, or if bothersome adverse effects (eg, changes in sexual function, diarrhea, excessive drowsiness, nausea, nervousness, tremors) occur.
  • Advise patients to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Advise patients and families, or caregivers of patients, to be alert for abnormal changes in mood or thinking and to immediately report any of the following to health care provider: agitation, akathisia (psychomotor restlessness), anxiety, change in mood, change in personality, hostility or aggressiveness, impulsivity, insomnia, irritability, panic attacks, or suicidal thoughts or behavior. Advise families and caregivers of patients to observe for emergence on a day-to-day basis because changes may be abrupt.
  • Advise patients that if medication needs to be discontinued, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
  • Instruct patients to avoid alcoholic beverages and sedatives or depressants (eg, diazepam) while taking this medication.
  • Advise patients that this medication may impair judgment, thinking, or motor skills, or cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Caution patients about the risk of serotonin syndrome with the concomitant use of citalopram and triptans, tramadol, or other serotonergic agents.
  • Advise patients to notify their health care provider if they become pregnant or intend to become pregnant during therapy, or if they are breast-feeding.

Copyright © 2009 Wolters Kluwer Health.

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