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Citalopram

N06A - Antidepressants ATC N06AB04 Small molecule approved 1998 Oral Black-box warning

JFDA label: lecital 40 tab

⚠ Black-Box Warning
  • Suicidality and antidepressants:

Mechanism of Action

A racemic bicyclic phthalane derivative, citalopram selectively inhibits serotonin reuptake in the presynaptic neurons and has minimal effects on norepinephrine or dopamine. Uptake inhibition of serotonin is primarily due to the S-enantiomer of citalopram. Displays little to no affinity for serotonin, dopamine, adrenergic, histamine, GABA, or muscarinic receptor subtypes.

Indications

Approved

  • Depression

Off-label

  • Binge eating disorder
  • Generalized anxiety disorder
  • Hot flashes
  • Obsessive-compulsive disorder (adults)
  • Obsessive-compulsive disorder (children/adolescents)
  • Panic disorder
  • Pathological gambling
  • Premature ejaculation

Contraindications

Source: Lexicomp

  • Additional contraindications (not in US labeling): Known QT interval prolongation or congenital long QT syndrome Absolute
  • Hypersensitivity to citalopram or any component of the formulation Absolute
  • concomitant use with pimozide Absolute
  • initiation of citalopram in a patient receiving linezolid or intravenous methylene blue Absolute
  • use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either citalopram or the MAO inhibitor) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (5)

Common bradycardia · hypotension · orthostatic hypotension · Prolonged Q-T interval on ECG · tachycardia

Nervous system disorders (13)

Very Common Drowsiness · insomnia

Common agitation · amnesia · anxiety · apathy · confusion · depression · Fatigue · lack of concentration · migraine · paresthesia · yawning

Renal and urinary disorders (4)

Common dysmenorrhea · Ejaculatory disorder · impotence · Polyuria

Metabolism and nutrition disorders (4)

Common amenorrhea · Decreased libido · weight gain · weight loss

Gastrointestinal disorders (11)

Very Common Nausea · xerostomia

Common abdominal pain · anorexia · Diarrhea · dysgeusia · dyspepsia · flatulence · increased appetite · sialorrhea · vomiting

Skin and subcutaneous tissue disorders (3)

Very Common Diaphoresis

Common pruritus · Skin rash

Musculoskeletal and connective tissue disorders (3)

Common arthralgia · myalgia · Tremor

Eye disorders (1)

Common Accommodation disturbance

General disorders and administration site conditions (1)

Common Fever

Respiratory, thoracic and mediastinal disorders (4)

Common cough · Rhinitis · sinusitis · upper respiratory tract infection

Dosing

Source: Lexicomp

Note: Doses >40 mg daily are not recommended due to the risk of QT prolongation. Depression: Adults 40 mg daily has not been demonstrated in clinical trials. Poor metabolizers of CYP2C19 or concurrent use of moderate-to-strong CYP2C19 inhibitors (eg, cimetidine, omeprazole): Maximum dose: 20 mg daily Binge eating disorder (off-label use): Oral: Initial: 20 mg once daily; may increase to 40 mg once daily. Doses up to 60 mg daily were evaluated; however, according to the manufacturer, dosing should not exceed 40 mg/day (McElroy 2003). Additional data are necessary to further define the role of citalopram in this condition. Generalized anxiety disorder (off-label use): Oral: Initial: 10 mg once daily; may progressively increase dose to 40 mg daily (Blank 2006; Lenze 2005). Additional data are necessary to further define the role of citalopram in this condition. Hot flashes (off-label use): Oral: Initial: 10 mg once daily; increase dose to 20 mg after 1 to 4 weeks. Doses as high as 40 mg daily have been studied (Kalay 2007; Suvanto-Luukkonen 2005) Obsessive compulsive disorder (off-label use): Oral: Initial: 20 mg once daily; may increase to target dose of 40 mg daily. Doses up to 60 mg daily were evaluated; however, according to the manufacturer, dosing should not exceed 40 mg/day (APA [Koran 2007]; Montgomery 2001). Panic disorder (off-label use): Oral: Initial: 10 mg daily for 7 days, then increase dose to 20 mg daily (Perna 2003; Stahl 2003). Consider further dosage adjustments based on response and tolerability. Mean dose in flexible-dose clinical trials was 20 to 40 mg daily; doses up to 60 mg daily have been evaluated (Leinonen 2000; Perna 2003; Seedat 2003; Stahl 2003; Wade 1997). Pathological gambling (off-label use): Oral: Initial: 10 mg once daily; may progressively increase to 40 mg daily. Doses up to 60 mg daily were evaluated; however, according to the manufacturer, dosing should not exceed 40 mg/day (Zimmerman 2002). Additional data are necessary to further define the role of citalopram in this condition. Premature Ejaculation (off-label use): Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability up to 40 mg/day (Althof 2014; Safarinejad 2006). Additional data may be necessary to further define the role of citalopram in this condition. Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4-6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescrib
(For additional information see "Citalopram: Pediatric drug information") Obsessive-compulsive disorder (off-label use): Children and Adolescents: Oral: 10-40 mg/day (Mukaddes 2003; Thomsen 1997; Thomsen 2001) Discontinuation of therapy: Refer to adult dosing. MAO inhibitor recommendations: Refer to adult dosing.
Depression: Elderly ≥60 years: Oral: Initial: 20 mg once daily; maximum dose in adults ≥60 years: 20 mg daily due to increased exposure and the risk of QT prolongation. Refer to adult dosing. Discontinuation of therapy: Refer to adult dosing. MAO inhibitor recommendations: Refer to adult dosing.
Mild-to-moderate impairment: No dosage adjustment necessary. Severe impairment: CrCl
Initial: 20 mg once daily; maximum recommended dose: 20 mg daily due to decreased clearance and the risk of QT prolongation

Warnings & Precautions

Source: Lexicomp

Suicidal thinking/behavior

Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Citalopram is not FDA approved for use in children. - The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy. - Prescriptions should be written for the smallest quantity consi

Bleeding risk

May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants. Bleeding (including GI bleeding) related to SSRI or SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

CNS depression

Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.

Fractures

Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).

Ocular effects

May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

QT prolongation

Causes dose-dependent QTc prolongation; torsade de pointes, ventricular tachycardia, and sudden death have been reported. Due to this risk, doses >40 mg/day are not recommended. Additionally, the maximum daily dose should not exceed 20 mg/day in certain populations (eg, CYP2C19 poor metabolizers, patients with hepatic impairment, elderly patients). Use is not recommended in patients with congenital long QT syndrome, bradycardia, recent MI, uncompensated heart failure, hypokalemia, and/or hypomagnesemia, or patients receiving concomitant medications which prolong the QT interval; if use is essential and cannot be avoided in these patients, ECG monitoring is recommended. Discontinue therapy in any patient with persistent QTc measurements >500 msec. Serum electrolytes, particularly potassium and magnesium, should be monitored prior to initiation and periodically during therapy in any patient at increased risk for significant electrolyte disturbances; hypokalemia and/or hypomagnesemia should be corrected prior to use.

Serotonin syndrome

Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

Sexual dysfunction

May cause or exacerbate sexual dysfunction.

SIADH and hyponatremia

SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium Disease-related concerns:

Heart failure

In a scientific statement from the American Heart Association, citalopram has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

Hepatic impairment

Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a maximum of 20 mg/day is recommended in any patient with hepatic impairment due to the risk of QT prolongation.

Mania/hypomania

May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Citalopram is not FDA approved for the treatment of bipolar depression.

Renal impairment

Use with caution in patients with severe renal impairment (pharmacokinetic information is not available). Clearance is decreased in patients with mild-to-moderate renal impairment, although no dosage adjustment is necessary.

Seizure disorders

Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

CYP2C19 poor metabolizers

Citalopram exposure and maximum concentrations are increased in CYP2C19 poor metabolizers; a maximum daily dose of 20 mg/day is recommended in these patients.

Elderly

Pharmacokinetics are altered in patients ≥60 years of age; a lower maximum dose of 20 mg/day is recommended in this population because of the risk of QT prolongation.

Pediatric

Citalopram is not FDA-approved for use in children; however, if used, monitor weight and growth regularly during therapy due to the potential for decreased appetite and weight loss with SSRI use.

Pregnancy

Use caution in pregnant patients; high doses of citalopram have been associated with teratogenicity in animals. Other warnings/precautions:

Discontinuation syndrome

Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation.. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2-5 days after treatment discontinuation and last 7-14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).

Electroconvulsive therapy (ECT)

Use with caution; no clinical studies have assessed the combined use of citalopram and ECT; may increase the risks (eg, cognitive adverse effects) associated with ECT; consider discontinuing, when possible, prior to ECT treatment.

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

Caution

Acceptable SSRI option; high doses (>20 mg) may carry more QT risk

Lactation

RID 3.0%

Citalopram and its active metabolites are present in breast milk. The relative infant dose (RID) of citalopram has been evaluated in numerous studies; the reported RID of citalopram ranges from 3% to 10% of the weight-adjusted maternal dose (maternal dose not stated; Berle 2011), and may be higher (Berle 2011; Sriraman 2015). In general, breastfeeding is considered acceptable when the RID is 25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Active metabolites of citalopr

Monitoring

Clinical pearlECG (patients at increased risk for QT-prolonging effects due to certain conditions); electrolytes (potassium and magnesium concentrations [prior to initiation and periodically during therapy in patients at increased risk for electrolyte abnormalities]); signs/symptoms of arrhythmias (eg, dizziness, palpitations, syncope); liver function tests and CBC with continued therapy; monitor patient periodically for symptom resolution; signs/symptoms of serotonin syndrome; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; akathisia

Chemistry & Properties

2D structure
FormulaC20H21FN2O
Molecular weight324.4 g/mol
IUPAC name1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3H-2-benzofuran-5-carbonitrile
CAS59729-33-8
PubChem CID2771
InChIKeyWSEQXVZVJXJVFP-UHFFFAOYSA-N
logP3.81 (XLogP 3.2)
Polar surface area36.26 Ų
H-bond acceptors / donors3 / 0
Drug-likeness (QED)0.84
Lipinski violations0
SMILESCN(C)CCCC1(c2ccc(F)cc2)OCc2cc(C#N)ccc21

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrantYes (logBB 0.99)

Enzyme interactions

EnzymeRoleDetail
CYP2C19Substrate
CYP2D6Substrate
CYP3A4Substrate

Receptor binding (top 12)

TargetActionAffinity
SERT Binding pKi 8.4
5-HT Transporter (SLC6A4) Binding pKi 8.4
SERT (SLC6A4) Inhibitor pKi 8.4
HISTAMINE H1 (HRH1) Binding pKi 6.5
H1 Binding pKi 6.3
5-HT2C (HTR2C) Binding pKi 6.3
adrenergic Alpha1 Binding pKi 5.9
Cholinergic, muscarinic M1 (CHRM1) Binding pKi 5.8
Alpha 1 Adrenergic Receptor Binding pKi 5.7
Muscarinic Acetylcholine Receptor Binding pKi 5.7
Norepinephrine transporter Binding pKi 5.2
5-HT2A (HTR2A) Binding pKi 5.2

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)OCT3 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)MRP1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drugSeverityManagement
Abarelix major
Abiraterone major
Alimemazine major
Anagrelide major
Apalutamide major
Arsenic trioxide major
Astemizole major
Bicalutamide major
Bosutinib major
Bupropion major
Cabozantinib major
Ceritinib major
Chloroquine major
Cimetidine major
Cisapride major
Clarithromycin major
Crizotinib major
Dasatinib major
Daunorubicin major
Daunorubicin (liposomal) major
Degarelix major
Dexfenfluramine major
Dextromethorphan major
Diethylpropion major
Dolasetron major
Doxepin major
Doxepin (topical) major
Doxorubicin major
Doxorubicin (liposomal) major
Encorafenib major
Entrectinib major
Enzalutamide major
Epirubicin major
Eribulin major
Erythromycin major
Esomeprazole major
Fedratinib major
Fenfluramine major
Fingolimod major
Fluconazole major

Showing 40 of 100+.

Registered Products (18)

BrandForm / strengthPackAgentCitizen (JOD)
Lecital 40 Tab Tablet 40 mg 15 tab pack varies Jordan Sweden Medical & Sterilization Co. 7.680
Cipratal F.C. Tab Film-Coated Tablet 20 mg 30 tab UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN 8.920
Citapram Tablet Tablet 20 mg 30 tab Pharma International Company/ Jordan 8.920
Lecital Tablet 20 mg 30 tab pack varies Jordan Sweden Medical & Sterilization Co. 8.920
CIPRAM TAB Tablet as( HBR) 20 mg 28 tab Abu Sharef Medical Stores 9.250
Citalopram Hexal Tablet 40 mg 20 tab The Jordan Drugstore Co 9.490
Citalogen Tablet 20 mg 30 tab Khoury Drug Store 11.800
Depran Tablet 20 mg 28 tab pack varies MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN 14.160
Cipratal F.C.Tab Film-Coated Tablet 40 mg 30 tab UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN 14.630
Citapram Tablet Tablet 40 mg 30 tab pack varies Pharma International Company/ Jordan 14.630
Lecital 40 tab Tablet 40 mg 30 tab pack varies Jordan Sweden Medical & Sterilization Co. 14.630
Talopram Tablet 20 mg 30 tab Dar Al Dawa Development and Investment Co Ltd/Jordan 16.000
Citalogen Tablet 40 mg 30 tab Khoury Drug Store 19.350
Depran Tablets Tablet 40 mg 28 tab MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN 19.600
Lecital Tablet 20 mg 300 tab pack varies Jordan Sweden Medical & Sterilization Co. 80.280
lecital 40 tab Tablet 40 mg 300 tab Jordan Sweden Medical & Sterilization Co. 131.670
Depran Tablet 20 mg 350 tab pack varies MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN 157.530
Citapram Tablet Tablet 40 mg 500 tab pack varies Pharma International Company/ Jordan 212.140