Citalopram (Lexi-Drugs)

ALERT: US Boxed Warning
  Suicidality and antidepressants:
Pronunciation

(sye TAL oh pram)

Brand Names: US

CeleXA

Brand Names: Canada

Abbott-Citalopram [DSC]; ACCEL-Citalopram; ACT Citalopram; AG-Citalopram; APO-Citalopram; Auro-Citalopram; BIO-Citalopram; CCP-Citalopram; CeleXA; Citalopram-10; Citalopram-20; Citalopram-40; Citalopram-ODAN [DSC]; CTP 30; DOM-Citalopram; ECL-Citalopram [DSC]; JAMP-Citalopram; Mar-Citalopram; MINT-Citalopram; MYLAN-Citalopram [DSC]; NAT-Citalopram; NRA-Citalopram; NU-Citalopram [DSC]; PHL-Citalopram [DSC]; PMS-Citalopram; Priva-Citalopram; Q-Citalopram [DSC]; RAN-Citalo; RIVA-Citalopram; SANDOZ Citalopram; SEPTA-Citalopram; TEVA-Citalopram; VAN-Citalopram

Dosing: Adult

Note: Maximum daily dose: Due to the risk of QT prolongation, the maximum recommended daily dose for all indications is 40 mg. A lower maximum daily dose of 20 mg is recommended in patients >60 years of age, those with significant hepatic impairment, and patients who are concurrently receiving medications that significantly increase citalopram levels (eg, cimetidine, omeprazole) or known poor metabolizers of CYP2C19 substrates. Initial dose and titration: In patients sensitive to side effects, some experts suggest a lower starting dose of 10 mg daily and gradual titration in increments of no more than 10 mg, particularly in patients with anxiety who are generally more sensitive to overstimulation effects (eg, anxiety, insomnia) with antidepressants (Hirsch 2018c; WFSBP [Bandelow 2012]).

Aggressive or agitated behavior associated with dementia (off-label use): Oral: Initial: 10 mg once daily; increase to 20 mg once daily after ≥3 days. In adults ≤60 years, may further increase dose based on response and tolerability up to 30 mg/day (Pollock 2002; Pollock 2007; Porsteinsson 2014); for adults >60 years, do not exceed the maximum dose of 20 mg/day.

Binge eating disorder (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years, may gradually increase dose based on response and tolerability at intervals ≥1 week to 40 mg once daily. Although doses up to 60 mg/day have been studied, due to safety considerations the recommended maximum dose is 40 mg/day for adults ≤60 years and 20 mg/day for adults >60 years (McElroy 2003).

Generalized anxiety disorder (off-label use): Oral: Initial: 10 mg once daily; may gradually increase dose based on response and tolerability in 10 mg increments at intervals ≥1 week to a maximum dose of 40 mg/day for adults ≤60 years and 20 mg/day for adults >60 years (Blank 2006; Varia 2002).

Major depressive disorder (unipolar): Oral: Initial: 20 mg once daily. In adults ≤60 years, may gradually increase dose based on response and tolerability at intervals ≥1 week to a maximum dose of 40 mg/day; for adults >60 years, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations.

Obsessive-compulsive disorder (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years, may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week to a maximum dose of 40 mg/day; for adults >60 years, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (APA [Koran 2007]; Montgomery 2001). Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered to be ≥6 weeks at maximum tolerated dose (Issari 2016).

Panic disorder (off-label use): Oral: Initial: 10 mg once daily for 3 to 7 days, then 20 mg once daily. In adults ≤60 years, may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week to a maximum of 40 mg/day; for adults >60 years, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (APA 2009b; Leinonen 2000; Perna 2001; Seedat 2003; Stahl 2003; Wade 1997).

Posttraumatic stress disorder (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years, may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week to a maximum dose of 40 mg once daily; for adults >60 years, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (English 2006; Tucker 2003).

Premature ejaculation (off-label use): Oral: Initial: 20 mg once daily. In adults ≤60 years, may gradually increase dose based on response and tolerability at intervals of ≥1 week (some experts suggest 3- to 4-week titration intervals [Khera 2018]) up to a maximum of 40 mg/day (Althof 2014; Atmaca 2002a; Safarinejad 2006); for adults >60 years, do not exceed the maximum dose of 20 mg/day.

Premenstrual dysphoric disorder (PMDD) (off-label use):

Continuous daily dosing regimen: Oral: Initial: 10 mg once daily; over the first month increase to usual effective dose of 20 mg once daily; in subsequent menstrual cycles, further dose increases (eg, in 10 mg increments per menstrual cycle) up to 40 mg/day may be necessary in some patients for optimal response (Casper 2018; Freeman 2002; Wikander 1998).

Intermittent regimens:

Luteal phase dosing regimen: Oral: Initial: 10 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month increase to usual effective dose of 20 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 30 mg/day during the luteal phase may be necessary in some patients for optimal response (Casper 2018; Freeman 2002; Wikander 1998).

Symptom-onset dosing regimen: Oral: Initial: 10 mg once daily from the day of symptom onset until a few days after the start of menses; over the first month increase to usual effective dose of 20 mg once daily; in a subsequent menstrual cycle a further increase to 30 mg/day may be necessary in some patients for optimal response (Casper 2018; Ravindran 2007).

Social anxiety disorder (off-label use): Oral: Initial: 10 to 20 mg once daily. In adults ≤60 years, after ~6 weeks may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week up to maximum of 40 mg/day; for adults >60 years, do not exceed the maximum dose of 20 mg/day. Daily doses that exceeded these limits have been studied but are not recommended due to safety considerations (Atmaca 2002b; Furmark 2005; Stein 2019; WFSBP [Bandelow 2012]).

Vasomotor symptoms associated with menopause (alternative agent) (off-label use): Oral: Initial: 10 mg once daily; may increase dose to 20 mg once daily after 1 week. In adults ≤60 years, doses as high as 40 mg/day have been studied; however, doses >20 mg/day have demonstrated little additional benefit and greater adverse effects (Barton 2010; Kalay 2007; NAMS 2015). For adults >60 years, do not exceed the maximum dose of 20 mg/day.

Dosage adjustments: For concomitant therapy with moderate to strong CYP2C19 inhibitors or other drugs that significantly increase citalopram levels (eg, cimetidine, omeprazole, voriconazole) and in persons who are known to be poor metabolizers of CYP2C19: Maximum dose: 20 mg/day.

Discontinuation of therapy: When discontinuing antidepressants, gradually taper the dose (eg, over 2 to 4 weeks) to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower titration (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, high doses of antidepressants or treatment duration >3 weeks (APA 2010; Hirsch 2018a). If intolerable withdrawal symptoms occur following a dose reduction, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Hirsch 2018b; Ogle 2013; WFSBP [Bauer 2013]).

Switching to or from an MAOI:

Allow 14 days to elapse between discontinuing an MAOI and initiation of citalopram.

Allow 14 days to elapse between discontinuing citalopram and initiation of an MAOI.

Dosing: Geriatric

Note: For patients >60 years of age, the maximum recommended dose is 20 mg/day due to the risk of QT prolongation.

Generalized anxiety disorder (off-label use): Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in 10 mg increments at intervals ≥1 week up to 20 mg/day. Doses up to 40 mg/day have been studied; however, according to the manufacturer, dosing should not exceed 20 mg/day. (Blank 2006; Lenze 2005)

Major depressive disorder (unipolar): Adults >60 years: Oral: Initial: 10 to 20 mg once daily (Marano 2015; VA/DoD 2016); maximum dose: 20 mg/day due to increased exposure and the risk of QT prolongation.

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Renal Impairment: Adult

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: CrCl <20 mL/minute: No dosage adjustment provided in manufacturer’s labeling (has not been studied); use caution.

Dosing: Hepatic Impairment: Adult

Maximum recommended dose: 20 mg daily due to decreased clearance and the risk of QT prolongation

Dosing: Pediatric

Note: Slower titration of dose every 2 to 4 weeks may minimize risk of SSRI associated behavioral activation, which has been shown to increase risk of suicidal behavior. Doses >40 mg are not recommended due to risk of QTc prolongation.

Depression: Limited data available; efficacy results variable: One randomized, placebo controlled trial has shown citalopram to be effective for the treatment of depression in pediatric patients (Wagner 2004); other controlled pediatric trials have not shown benefit (Sharp 2006; von Knorring 2006; Wagner 2005). Some experts recommend the following doses (Dopheide 2006): Oral:

Children 7 to ≤11 years: Initial: 10 mg/day given once daily; increase dose slowly by 5 mg/day every 2 weeks as clinically needed; dosage range: 20 to 40 mg/day

Children and Adolescents ≥12 years: Initial: 20 mg/day given once daily; increase dose slowly by 10 mg/day every 2 weeks as clinically needed; dosage range: 20 to 40 mg/day

Obsessive-compulsive disorder: Limited data available: Several open label trials have been published (Mukaddes 2003; Thomsen 1997; Thomsen 2001). Some experts recommend the following doses: Oral:

Children 7 to ≤11 years: Initial: 5 to 10 mg/day given once daily; increase dose slowly by 5 mg/day every 2 weeks as clinically needed; dosage range: 10 to 40 mg/day

Children and Adolescents ≥12 years: Initial: 10 to 20 mg/day given once daily; increase dose slowly by 10 mg/day every 2 weeks as clinically needed; dosage range: 10 to 40 mg/day

Note: Higher mg/kg doses are needed in children compared to adolescents.

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 reemerging 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 prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of citalopram.

Allow 14 days to elapse between discontinuing citalopram and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Use with other MAO inhibitors (linezolid or IV methylene blue):

Do not initiate citalopram in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.

If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving citalopram and potential benefits outweigh potential risks, discontinue citalopram promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume citalopram 24 hours after the last dose of linezolid or IV methylene blue.

Dosing: Renal Impairment: Pediatric

Specific recommendations in pediatric patients are not available; based on experience in adult patients, in mild to moderate impairment, no adjustment needed, and in severe impairment, use with caution (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Specific recommendations in pediatric patients are not available; based on experience in adult patients, consider reduced daily doses due to increased serum concentrations and the risk of QT prolongation.

Use: Labeled Indications

Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder

Use: Off-Label: Adult

  Aggressive or agitated behavior associated with dementiaLevel of Evidence [A]

Data from a randomized, double-blind, placebo-controlled study support the use of citalopram in the treatment of agitation associated with dementia Ref.

  Binge eating disorderLevel of Evidence [C, G]

Data from a limited number of patients studied suggest that citalopram may be beneficial for the treatment of binge eating disorder by reducing binge episode frequency, weight, and severity of illness; however, average doses used (>40 mg) are no longer recommended due to an increased risk of cardiovascular effects Ref.

Based on the American Psychiatric Association practice guideline for the treatment of patients with eating disorders and World Federation of Societies of Biological Psychiatry guidelines for the treatment of the pharmacologic treatment of eating disorders, citalopram given for binge eating disorder is effective and recommended; however, these guidelines were drafted prior to changes in the citalopram labeling regarding dose-related QT prolongation. Access Full Off-Label Monograph

  Generalized anxiety disorderLevel of Evidence [C]

Data from a limited number of adult and geriatric patients suggest that citalopram may be beneficial for the treatment of generalized anxiety disorder RefAccess Full Off-Label Monograph

  Obsessive-compulsive disorderLevel of Evidence [B, G]

Data from a randomized, double-blind, placebo-controlled study support the use of citalopram in the treatment of OCD Ref.

Based on the American Psychiatric Association practice guideline for the treatment of patients with obsessive-compulsive disorder, the use of an SSRI, such as citalopram, is an effective and recommended treatment option for patients with this condition.

  Panic disorderLevel of Evidence [B, G]

Data from 3 double-blind, randomized, parallel-group, placebo-controlled, multicenter studies and 2 single-blind, flexible-dose studies support the use of citalopram in the treatment of panic disorder Ref.

Based on the American Psychiatric Association guidelines for the treatment of patients with panic disorder and the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, citalopram is effective and recommended in the management of panic disorder.

  Posttraumatic stress disorderLevel of Evidence [C, G]

Data from a double-blind, randomized, placebo- and active-controlled trial and an open-label study suggest that the use of citalopram may be beneficial in the treatment of PTSD Ref.

Based on the American Psychiatric Association guidelines for the treatment of patients with acute stress disorder and PTSD and the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, SSRIs are effective and recommended as first-line treatment for PTSD. The guidelines provide no recommendations specific to citalopram because at the time of publication controlled studies with citalopram were not available; however, clinical consensus suggests SSRIs are equivalent in efficacy. Access Full Off-Label Monograph

  Premature ejaculationLevel of Evidence [C, G]

Data from a limited number of patients in controlled trials suggest that citalopram may be beneficial for the treatment of premature ejaculation Ref.

According to the International Society for Sexual Medicine guidelines, citalopram is effective and recommended in the management of premature ejaculation; however, paroxetine may have a more robust effect. Access Full Off-Label Monograph

  Premenstrual dysphoric disorderLevel of Evidence [C, G]

Data from a limited number of patients studied suggest that citalopram may be beneficial for the treatment of premenstrual dysphoric disorder as a continuous daily dose or during the luteal phase Ref.

Based on the International Society for Premenstrual Disorders auditable standards for diagnosis and management of premenstrual disorder, SSRIs are effective and recommended in the management of premenstrual dysphoric disorder.

  Social anxiety disorderLevel of Evidence [C, G]

Data from a limited number of clinical trials suggest that citalopram may be beneficial for the treatment of social anxiety disorder Ref.

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, SSRIs such as citalopram are effective and recommended for the management of social anxiety disorder.

  Vasomotor symptoms associated with menopauseLevel of Evidence [B, G]

Data from 2 randomized, placebo-controlled trials and a meta-analysis support the use of citalopram in the treatment of vasomotor symptoms (eg, hot flashes) in peri- or postmenopausal women Ref.

Based on the American Association of Clinical Endocrinologists and American College of Endocrinology position statement on menopause, the Endocrine Society guideline on the treatment of symptoms of menopause, and the North American Menopause Society position statement on nonhormonal management of menopause-associated vasomotor symptoms, SSRIs (including citalopram) are an effective and recommended alternative for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy. Based on the American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline, SSRIs may be used to help mitigate vasomotor symptoms of premature menopause in women previously treated for breast cancer. Access Full Off-Label Monograph

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Anxiety Disorders:

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” November 2004

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Panic Disorder,” 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care,” 2012

Bipolar Disorder:

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Clinical Guidelines for the Management of Major Depressive Disorder in Adults,” October 2009

National Collaborating Centre for Mental Health (NCCMH), “Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition).” 2010.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder and Treatment of Chronic Depressive Disorders and Subthreshold Depressions,” 2002.

Obsessive-Compulsive Disorder:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder, 2007

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

Premenstrual Dysphoric Disorder:

International Society for Premenstrual Disorders (ISPD), “ISPD auditable standards for diagnosis and management of premenstrual disorder,” December 2016

Vasomotor Symptoms Associated with Menopause:

Endocrine Society (ES), Treatment of Symptoms of the Menopause, 2015

North American Menopause Society (NAMS), Nonhormonal management of menopause-associated vasomotor symptoms, 2015

Administration: Oral

May be administered without regard to food.

Administration: Pediatric

Oral: May be administered without regard to meals

Dietary Considerations

May be taken without regard to food.

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, fatigue, dry mouth, lack of appetite, loss of strength and energy, insomnia, tremors, constipation, common cold symptoms, diarrhea, sweating a lot, or yawning. Have patient report immediately to prescriber signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), agitation, panic attacks, mood changes, angina, tachycardia, abnormal heartbeat, bradycardia, shortness of breath, dizziness, passing out, seizures, sexual dysfunction, weight gain, weight loss, menstrual changes, vision changes, eye pain, eye irritation, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020822s047lbl.pdf, must be dispensed with this medication.

Contraindications

Hypersensitivity to citalopram or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either citalopram or the MAO inhibitor); initiation of citalopram in a patient receiving linezolid or intravenous methylene blue; concomitant use with pimozide

Canadian labeling: Additional contraindications (not in US labeling): Known QT interval prolongation or congenital long QT syndrome

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: 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 to 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 health care 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 consistent with good patient care. The patient’s family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• 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 <110 mmol/L), predominately in the elderly; reversible with discontinuation of treatment. Volume depletion and/or concurrent use of diuretics likely increases risk.

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 to 5 days after treatment discontinuation and last 7 to 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.

Geriatric Considerations

AUC was increased by 23% to 30% and half-life increased by 30% to 50% in older adults >60 years of age compared to younger adults. Due to the risk of QT prolongation associated with higher doses of citalopram, a lower maximum daily dose of 20 mg/day in recommended in all older adults.

A seven- to eightfold variation in citalopram S(+) (active) and R(-) enantiomer concentrations have been reported in the elderly. The racemic citalopram concentration-to-dose ratio was 1.8 times greater in elderly patients compared to younger patients. The elderly are also more prone to SSRI/SNRI-induced hyponatremia.

In patients with hepatic impairment, clearance was decreased, while half-life was significantly increased. Mild-to-moderate renal impairment may reduce clearance of citalopram (17% reduction noted in trials). No pharmacokinetic information is available concerning patients with severe renal impairment. Pharmacokinetics was also significantly altered in poor CYP2C19 metabolizers.

A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence “suggestive” of efficacy but not of sufficient strength to “confirm” efficacy (Nelson 2011). Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects.

Warnings: Additional Pediatric Considerations

Selective serotonin reuptake inhibitor (SSRI)-associated behavioral activation (ie, restlessness, hyperkinesis, hyperactivity, agitation) is two- to threefold more prevalent in children compared to adolescents; it is more prevalent in adolescents compared to adults. Somnolence (including sedation and drowsiness) is more common in adults compared to children and adolescents (Safer, 2006). SSRI-associated vomiting is two- to threefold more prevalent in children compared to adolescents and is more prevalent in adolescents compared to adults (Safer, 2006).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Citalopram and its metabolites cross the human placenta (Heikkinen, Ekblad, Kero 2002). An increased risk of teratogenic effects, including cardiovascular defects, may be associated with maternal use of citalopram or other SSRIs; however, available information is conflicting. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.

Due to pregnancy-induced physiologic changes, women who are pregnant may require adjusted doses of citalopram to achieve euthymia (Heikkinen, Ekblad, Kero 2002). The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Breast-Feeding Considerations

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 <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015). When an RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Active metabolites of citalopram can also be detected in breast milk. Peak milk concentrations of citalopram and desmethylcitalopram occur 4 and 6 hours, respectively, after the maternal dose in women on chronic therapy (Rampono 2000). However, avoiding breastfeeding during the expected peak concentrations will generally not decrease infant exposure significantly for antidepressants with long half-lives (Berle 2011). Although the absolute infant plasma concentrations are generally negligible, in some cases the infant plasma concentration of citalopram was up to 10% of the maternal concentration (Berle 2011).

Excessive somnolence, decreased feeding, and weight loss have been noted in infants exposed to citalopram from breast milk. Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015). Maternal use of an SSRI during pregnancy may cause delayed lactogenesis (Marshall 2010).

When first initiating an antidepressant in a breastfeeding woman, agents other than citalopram are preferred. Women successfully treated with citalopram during pregnancy may continue use while breastfeeding if there are no other contraindications (Berle 2011; Sriraman 2015). According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Central nervous system: Drowsiness (18%; dose related), insomnia (15%; dose related)

Dermatologic: Diaphoresis (11%; dose related)

Gastrointestinal: Nausea (21%), xerostomia (20%)

1% to 10%:

Cardiovascular: Prolonged Q-T interval on ECG (2%), hypotension (≥1%), orthostatic hypotension (≥1%), tachycardia (≥1%), bradycardia (1%)

Central nervous system: Fatigue (5%; dose related), anxiety (4%), agitation (3%), yawning (2%; dose related), amnesia (≥1%), apathy (≥1%), confusion (≥1%), depression (≥1%), lack of concentration (≥1%), migraine (≥1%), paresthesia (≥1%)

Dermatologic: Skin rash (≥1%), pruritus (≥1%)

Endocrine & metabolic: Decreased libido (1% to 4%), amenorrhea (≥1%), weight gain (≥1%), weight loss (≥1%)

Gastrointestinal: Diarrhea (8%), dyspepsia (5%), anorexia (4%), vomiting (4%), abdominal pain (3%), dysgeusia (≥1%), flatulence (≥1%), increased appetite (≥1%), sialorrhea (≥1%)

Genitourinary: Ejaculatory disorder (6%), dysmenorrhea (3%), impotence (3%; dose related)

Neuromuscular & skeletal: Tremor (8%), arthralgia (2%), myalgia (2%)

Ophthalmic: Accommodation disturbance (≥1%)

Renal: Polyuria (≥1%)

Respiratory: Rhinitis (5%), upper respiratory tract infection (5%), sinusitis (3%), cough (≥1%)

Miscellaneous: Fever (2%)

<1%, postmarketing, and/or case reports: Abnormal gait, abnormal lacrimation, abnormal serum prolactin levels, acne vulgaris, acute renal failure, aggressive behavior, akathisia, alopecia, altered serum glucose, anaphylaxis, anemia, angina pectoris, angioedema, angle-closure glaucoma, arthritis, asthma, ataxia, atrial fibrillation, blepharoptosis, blood coagulation disorder, breast hypertrophy, bronchitis, bronchospasm, bruxism, bundle branch block, bursitis, cardiac arrest, cardiac failure, cataract, catatonia, cellulitis, cerebrovascular accident, cholecystitis, cholelithiasis, choreoathetosis, colitis, conjunctivitis, dehydration, delirium, delusions, depersonalization, dermatitis, diplopia, diverticulitis, drug dependence, dry eye syndrome, duodenal ulcer, dyskinesia, dysphagia, dyspnea, dystonia, dysuria, ecchymoses, eczema, emotional lability, epistaxis, eructation, erythema multiforme, esophagitis, euphoria, extrapyramidal reaction, extrasystoles, eye pain, facial edema, flu-like symptoms, flushing, galactorrhea, gastric ulcer, gastritis, gastroenteritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, gingivitis, glossitis, goiter, granulocytopenia, gynecomastia, hallucination, hematuria, hemolytic anemia, hemorrhoids, hepatic necrosis, hepatitis, hiccups, hot flash, hyperbilirubinemia, hyperesthesia, hyperkinesia, hypersensitivity reaction, hypertension, hypertonia, hypertrichosis, hypochromic anemia, hypoesthesia, hypoglycemia, hypohidrosis, hypokalemia, hypokinesia, hyponatremia, hypoprothrombinemia, hypothyroidism, increased libido, increased liver enzymes, increased serum alkaline phosphatase, increased thirst, involuntary muscle movements, ischemic heart disease, jaundice, keratitis, laryngitis, leg cramps, leukocytosis, leukopenia, lymphadenopathy, lymphocytopenia, lymphocytosis, mastalgia, melanosis, myasthenia, mydriasis, myocardial infarction, myoclonus, nephrolithiasis, neuralgia, neuroleptic malignant syndrome (Stevens 2008), nightmares, nystagmus, obesity, oliguria, osteoporosis, pancreatitis, panic attack, paranoia, peripheral edema, phlebitis, photophobia, pneumonia, pneumonitis, priapism, pruritus ani, psoriasis, psychosis, pulmonary embolism, purpura, pyelonephritis, Raynaud’s phenomenon (Khouri 2016; Peiró 2007), renal pain, rhabdomyolysis, rigors, seasonal allergic rhinitis, seizure, serotonin syndrome, skeletal pain, skin discoloration, skin photosensitivity, stomatitis, stupor, syncope, thrombocytopenia, thrombosis, tinnitus, tonic-clonic seizures, torsades de pointes, toxic epidermal necrolysis, transient ischemic attacks, urinary incontinence, urinary retention, urticaria, vaginal hemorrhage, ventricular arrhythmia, vertigo, withdrawal syndrome, xeroderma

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2C19 (major), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)

Drug Interactions 

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider therapy modification

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Blood Glucose Lowering Agents: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination

BuPROPion: May enhance the adverse/toxic effect of Citalopram. Specifically, the risk for seizures and serotonin syndrome may be increased with this combination. BuPROPion may increase the serum concentration of Citalopram. Management: Initiate citalopram at the lower end of the normal dose range in patients receiving bupropion and consider limiting the maximum citalopram adult dose to 20 mg/day during concomitant bupropion treatment. Risk D: Consider therapy modification

BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Risk D: Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Citalopram. Risk C: Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Citalopram. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

CYP2C19 Inducers (Moderate): May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP2C19 Inhibitors (Moderate): May increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Risk X: Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. Risk D: Consider therapy modification

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Dosulepin: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dosulepin. Risk X: Avoid combination

Doxepin-Containing Products: Citalopram may enhance the QTc-prolonging effect of Doxepin-Containing Products. Citalopram may enhance the serotonergic effect of Doxepin-Containing Products. This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Escitalopram: May enhance the QTc-prolonging effect of Citalopram. Escitalopram may enhance the serotonergic effect of Citalopram. This could result in serotonin syndrome. Risk X: Avoid combination

Esomeprazole: May increase the serum concentration of Citalopram. Risk C: Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Fluconazole: May enhance the QTc-prolonging effect of Citalopram. Fluconazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with fluconazole, which is a strong CYP2C19 inhibitor. Risk D: Consider therapy modification

Gilteritinib: Citalopram may enhance the QTc-prolonging effect of Gilteritinib. Gilteritinib may diminish the therapeutic effect of Citalopram. Management: Avoid use of this combination if possible. If use is necessary, monitor for reduced response to citalopram and for QTc prolongation and arrhythmias. Patients with other risk factors may be at greater risk for these serious toxicities. Risk D: Consider therapy modification

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk D: Consider therapy modification

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible. If clinically acceptable, wait at least 2 weeks (5 weeks for fluoxetine) after SSRI discontinuation to initiate linezolid. Risk D: Consider therapy modification

Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Risk D: Consider therapy modification

Lithium: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Risk D: Consider therapy modification

Lofexidine: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. Lofexidine may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Risk D: Consider therapy modification

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk X: Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Risk C: Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Risk D: Consider therapy modification

MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Mexiletine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Mexiletine. Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Omeprazole: May increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with omeprazole. Risk D: Consider therapy modification

Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Opioid Agonists: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination

QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide. Risk C: Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Gilteritinib. Risk C: Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone; Lofexidine. Risk C: Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): Citalopram may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Citalopram. Exceptions: Fluconazole. Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Citalopram may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Citalopram. Exceptions: Voriconazole. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Citalopram. Risk C: Monitor therapy

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.Risk C: Monitor therapy

Serotonin Reuptake Inhibitor/Antagonists: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin Reuptake Inhibitor/Antagonists. This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity. Risk D: Consider therapy modification

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

St John’s Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Citalopram. Tricyclic Antidepressants may increase the serum concentration of Citalopram. Citalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with citalopram. Exceptions: Doxepin (Systemic); Doxepin (Topical).Risk D: Consider therapy modification

Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Voriconazole: Citalopram may enhance the QTc-prolonging effect of Voriconazole. Voriconazole may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with voriconazole, which is a moderate CYP2C19 inhibitor. Risk D: Consider therapy modification

Monitoring Parameters

ECG (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

Advanced Practitioners Physical Assessment/Monitoring

Assess mental status prior to initiation; close follow-up during first few months of treatment should provide ongoing evaluation of mood, with attention to any signs of clinical worsening, suicide ideation, sedation, anxiety, poor social functioning, mania, or panic attack. Obtain baseline EKG prior to initiation in patients at risk of prolonged QT, and then again at 1 month, and again once at target dose. Monitor for signs of hyponatremia as this has been infrequently reported, increased bleeding times, and sexual dysfunction. GI side effects are usually transient and will stop after 1-2 weeks of usage. Taper dosage slowly when discontinuing.

Nursing Physical Assessment/Monitoring

Assess mental status: Mood (depression or mania), signs of clinical worsening, suicide ideation, anxiety, social functioning, sleep pattern, loss of appetite, or any new physical complaint. Assess gastrointestinal tolerance.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral:

Generic: 10 mg/5 mL (240 mL)

Tablet, Oral:

CeleXA: 10 mg

CeleXA: 20 mg, 40 mg [scored]

Generic: 10 mg, 20 mg, 40 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

CeleXA: 20 mg, 40 mg

CTP 30: 30 mg

Generic: 10 mg, 20 mg, 40 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N06AB04
Generic Available (US)

Yes

Pricing: US

Solution (Citalopram Hydrobromide Oral)

10 mg/5 mL (per mL): $0.49 – $0.98

Tablets (CeleXA Oral)

10 mg (per each): $10.89

20 mg (per each): $11.35

40 mg (per each): $11.85

Tablets (Citalopram Hydrobromide Oral)

10 mg (per each): $2.32 – $2.62

20 mg (per each): $2.42 – $2.73

40 mg (per each): $2.53 – $3.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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.

Pharmacodynamics/Kinetics

Onset of action: Depression: The onset of action is 1 to 4 weeks; however, individual response varies greatly and full response may not be seen until 8 to 12 weeks after initiation of treatment.

Duration: 1 to 2 days

Distribution: Vd: 12 L/kg

Protein binding, plasma: ~80%

Metabolism: Extensively hepatic, via CYP3A4 and 2C19 (major pathways), and 2D6 (minor pathway); metabolized to demethylcitalopram (DCT), didemethylcitalopram (DDCT), citalopram-N-oxide, and a deaminated propionic acid derivative, which are at least eight times less potent than citalopram

Bioavailability: 80%; tablets and oral solution are bioequivalent

Half-life elimination: 24 to 48 hours (average: 35 hours); doubled with hepatic impairment and increased by 30% (following multiple doses) to 50% (following single dose) in elderly patients (≥60 years)

Time to peak, serum: 1 to 6 hours, average within 4 hours

Excretion: Urine (Citalopram 10% and DCT 5%)

Note: Clearance was decreased, while half-life was significantly increased in patients with hepatic impairment. Mild to moderate renal impairment may reduce clearance (17%) and prolong half-life of citalopram. No pharmacokinetic information is available concerning patients with severe renal impairment. AUC and half-life were significantly increased in elderly patients (≥60 years), and in poor CYP2C19 metabolizers, steady state Cmax and AUC was increased by 68% and 107%, respectively.

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Oral clearance decreased 17% in mild to moderate renal impairment.

Hepatic function impairment: Oral clearance decreased 37% and half-life doubled in reduced hepatic function.

Geriatric: 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.

Local Anesthetic/Vasoconstrictor Precautions

Although caution should be used in patients taking tricyclic antidepressants, no interactions have been reported with vasoconstrictors and citalopram, a nontricyclic antidepressant which acts to increase serotonin; no precautions appear to be needed

Citalopram is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.

Dental Health Professional Considerations

Problems with SSRI-induced bruxism have been reported and may preclude their use; clinicians attempting to evaluate any patient with bruxism or involuntary muscle movement, who is simultaneously being treated with an SSRI drug, should be aware of the potential association.

Also see Local Anesthetic/Vasoconstrictor Precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Premarketing trials reported abnormal taste. See Effects on Bleeding and Dental Health Professional Considerations.

Effects on Bleeding

Selective serotonin reuptake inhibitors, such as citalopram, may impair platelet aggregation due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication. The risk of a bleeding complication can be increased by coadministration of other antiplatelet agents, such as NSAIDs and aspirin.

Index Terms

Citalopram Hydrobromide; Nitalapram

FDA Approval Date
July 17, 1998
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Shams T, Firwana B, Habib F, et al. SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials. J Gen Intern Med. 2014;29(1):204-213. doi: 10.1007/s11606-013-2535-9.[PubMed 23888328]

Shelton RC. Steps following attainment of remission: discontinuation of antidepressant therapy. Prim Care Companion J Clin Psychiatry. 2001;3(4):168-174.[PubMed 15014601]

Sriraman NK, Melvin K, Meltzer-Brody S. ABM clinical protocol #18: use of antidepressants in breastfeeding mothers. Breastfeed Med. 2015;10(6):290-299.[PubMed 26204124]

Stahl SM, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2003;64(11):1322-1327.[PubMed 14658946]

Stein MB, Taylor CT. Approach to treating social anxiety disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 10, 2019.

Stevens DL, “Association Between Selective Serotonin-Reuptake Inhibitors, Second-Generation Antipsychotics, and Neuroleptic Malignant Syndrome,” Ann Pharmacother, 2008, 42(9):1290-7.[PubMed 18628446]

Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011. doi: 10.1210/jc.2015-2236.[PubMed 26444994]

Thomsen PH. Child and adolescent obsessive-compulsive disorder treated with citalopram: findings from an open trial of 23 cases. J Child Adolesc Psychopharmacol. 1997;7(3):157-166.[PubMed 9466233]

Thomsen PH, Ebbesen C, Persson C. Long-term experience with citalopram in the treatment of adolescent OCD. J Am Acad Child Adolesc Psychiatry. 2001;40(8):895-902.[PubMed 11501688]

Tucker P, Potter-Kimball R, Wyatt DB, et al. Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo. Psychopharmacol Bull. 2003;37(3):135-149.[PubMed 14608246]

US Department of Veterans Affairs/Department of Defense (VA/DoD). VA/DoD clinical practice guideline for the management of major depressive disorder. https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFINAL82916.pdf. Updated April 2016. Accessed August 2, 2018.

Varia I, Rauscher F. Treatment of generalized anxiety disorder with citalopram. Int Clin Psychopharmacol. 2002;17(3):103-107.[PubMed 11981350]

Wade AG, Lepola U, Koponen HJ, Pedersen V, Pedersen T. The effect of citalopram in panic disorder. Br J Psychiatry. 1997;170:549-553.[PubMed 9330022]

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Wikander I, Sundblad C, Andersch B, et al. Citalopram in premenstrual dysphoria: is intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle? J Clin Psychopharmacol. 1998;18(5):390-398.[PubMed 9790157]

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Brand Names: International

Ansiben (CR, DO, GT, HN, NI, PA, SV); Ansiodex (PY); Arpolax (BD, HK); Celapram (AU, NZ); Celica (AU); Ceropam (EG); Cimal (CL); Ciprager (IE); Cipram (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, GR, HK, ID, IQ, IR, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, PK, QA, SA, SC, SD, SG, SL, SN, SY, TH, TN, TR, TW, TZ, UG, YE, ZM, ZW); Cipramax (EG); Cipramil (AU, BE, BR, CL, CN, DE, DK, EE, FI, GB, IE, IL, LU, NL, NO, NZ, PE, PL, RU, SE, UA, VN, ZA); Ciprotan (IE); Ciram (SG); Citaalogen (JO); Citadep (LK); Cital (MY); Citalo (EG); Citalogen (AE, BH, KW, QA, SA); Citalon (HR); Citalvir (ES); Citao (TW); Citapram (BD); Citazone (CO); Citopam (IN, LK); Citox (MX); Citrol (IE); Denyl (BR); Depaway (EG); Feliz (LK, PH); Humorap (PY); Kitapram (TW); Lecital (BH, EG, LB, QA, SA); Linisan (RO); Lopram (AE, BH, KW, QA); Lowdep (VN); Oropram (MT); Pram (UA); Prepram (MX); Prisdal (ES); Psiconor (UY); Recital (IL); Sepram (FI); Seropram (AT, BG, CH, CZ, ES, FR, GR, HU, IT, MX, VE); Starcitin (HR); Talam (AU, HK); Talosin (MT); Xylorane (MX); Zentius (AR, CL, EC); Zinetron (MX)

Citalopram (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(sye TAL oh pram)

Brand Names: US

CeleXA

Brand Names: Canada

Celexa

Warning
  • For all patients taking this drug:
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • Children:
  • This drug is not approved for use in children. However, the doctor may decide the benefits of taking this drug outweigh the risks. If your child has been given this drug, ask the doctor for information about the benefits and risks. Talk with the doctor if you have questions about giving this drug to your child.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to citalopram or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • If you are taking any of these drugs: Escitalopram or pimozide.
  • If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson’s disease like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If you have any of these health problems: Long QTc on ECG or other heartbeat that is not normal, slow heartbeat, or low potassium or magnesium levels.
  • If you have heart failure (weak heart).
  • If you have had a recent heart attack.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • For all patients taking this drug:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • An unsafe heartbeat that is not normal (long QT on ECG) has happened with this drug. Sudden deaths have rarely happened in people taking this drug. Talk with the doctor.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • In depression, sleep and appetite may get better soon after starting this drug. Other low mood signs may take up to 4 weeks to get better.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • Some people may have a higher chance of eye problems with this drug. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
  • This drug can cause low sodium levels. Very low sodium levels can be life-threatening, leading to seizures, passing out, trouble breathing, or death. Talk with the doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant, plan on getting pregnant, or are breast-feeding. You will need to talk about the benefits and risks to you and the baby.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
  • Children:
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Chest pain or pressure.
  • Fast, slow, or abnormal heartbeat.
  • Shortness of breath.
  • Dizziness or passing out.
  • Seizures.
  • A change in weight without trying.
  • Sex problems like lowered interest in sex or ejaculation problems.
  • Erection that lasts more than 4 hours.
  • Period (menstrual) changes.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if you take this drug with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Upset stomach.
  • Feeling sleepy.
  • Dry mouth.
  • Not hungry.
  • Feeling tired or weak.
  • Diarrhea.
  • Constipation.
  • Trouble sleeping.
  • Shakiness.
  • Sweating a lot.
  • Yawning.
  • Signs of a common cold.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Oral solution:
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Citalopram (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(sye TAL oh pram)

Brand Names: US

CeleXA

Brand Names: Canada

Celexa

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug is not approved for use in children. However, the doctor may decide the benefits of taking this drug outweigh the risks. If your child has been given this drug, ask the doctor for information about the benefits and risks. Talk with the doctor if you have questions about giving this drug to your child.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is taking any of these drugs: Linezolid or methylene blue.
  • If your child is taking any of these drugs: Escitalopram or pimozide.
  • If your child is taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask the doctor or pharmacist if you are not sure.
  • If your child has taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for certain other health problems in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If your child has any of these health problems: Long QTc on ECG or other heartbeat that is not normal, slow heartbeat, or low potassium or magnesium levels.
  • If your child has heart failure (weak heart).
  • If your child has had a recent heart attack.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • An unsafe heartbeat that is not normal (long QT on ECG) has happened with this drug. Sudden deaths have rarely happened in people taking this drug. Talk with the doctor.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • In depression, sleep and appetite may get better soon after starting this drug. Other low mood signs may take up to 4 weeks to get better.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • Some people may have a higher chance of eye problems with this drug. The doctor may want your child to have an eye exam to see if your child has a higher chance of these eye problems. Call the doctor right away if your child has eye pain, change in eyesight, or swelling or redness in or around the eye.
  • This drug can cause low sodium levels. Very low sodium levels can be life-threatening, leading to seizures, passing out, trouble breathing, or death. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Chest pain or pressure.
  • Fast, slow, or abnormal heartbeat.
  • Shortness of breath.
  • Dizziness or passing out.
  • Seizures.
  • A change in weight without trying.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if your child takes this drug with drugs for depression, migraines, or certain other drugs. Call your child’s doctor right away if your child has agitation; change in balance; confusion; hallucinations; fever; a fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • If your child has menstrual periods:
  • Period (menstrual) changes.
  • If your child is or may be sexually active:
  • Sex problems like lowered interest in sex or ejaculation problems.
  • Erection that lasts more than 4 hours.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Feeling sleepy.
  • Not hungry.
  • Feeling tired or weak.
  • Diarrhea.
  • Constipation.
  • Shakiness.
  • Sweating a lot.
  • Yawning.
  • Upset stomach.
  • Trouble sleeping.
  • Dry mouth.
  • Signs of a common cold.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with or without food.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Oral solution:
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.