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Desipramine: Drug information

Desipramine: Drug information
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For additional information see "Desipramine: Patient drug information" and "Desipramine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Suicidality and antidepressant drugs:

Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of desipramine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Closely observe and appropriately monitor patients of all ages who are started on antidepressant therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescribing health care provider. Desipramine is not approved for use in pediatric patients.

Brand Names: US
  • Norpramin
Brand Names: Canada
  • DOM-Desipramine;
  • PMS-Desipramine
Pharmacologic Category
  • Antidepressant, Tricyclic (Secondary Amine)
Dosing: Adult
Diabetic neuropathy

Diabetic neuropathy (off-label use): Oral: Initial: 12.5 mg once daily at bedtime, then increase based on response and tolerability in 12.5 to 25 mg increments every 2 to 3 days to a maximum dose of 250 mg/day. Divide into twice daily doses if needed for tolerability (Ref).

Functional dyspepsia

Functional dyspepsia (alternative agent) (off-label use):

Note: May be used to augment or replace proton pump inhibitor therapy in partial and nonresponders who have been tested for H. pylori and treated if positive (Ref).

Oral: Dosing based on expert opinion. Initial: 25 mg once daily at bedtime. May increase dose based on response and tolerability at ≥1-week intervals up to a maximum of 50 mg/day (Ref).

Irritable bowel syndrome–associated pain and global symptoms

Irritable bowel syndrome–associated pain and global symptoms (off-label use):

Note: Due to their effect on intestinal transit, tricyclic antidepressants should be used cautiously in patients with constipation (Ref).

Oral: Initial: 10 to 25 mg daily at bedtime; may gradually increase dose based on response and tolerability, to a recommended dose of 25 to 100 mg/day (Ref). Some experts recommend 3 to 4 weeks of therapy before increasing the dose (Ref).

Major depressive disorder

Major depressive disorder (unipolar): Oral: Initial dose: 25 to 50 mg once daily or in divided doses (Ref); increase based on tolerance and response; usual maintenance dose: 100 to 200 mg once daily or in divided doses; doses up to 300 mg/day may be necessary in severely depressed patients (maximum: 300 mg/day).

Postherpetic neuralgia

Postherpetic neuralgia (off-label use): Oral: Initial: 12.5 to 25 mg once or twice daily; increase dose every 2 to 7 days based on response and tolerability up to 150 mg/day (Ref).

Discontinuation of therapy: For brief treatment (eg, 2 to 3 weeks) may taper over 1 to 2 weeks; <2 weeks treatment generally does not warrant tapering (Ref). When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). Reasons for a slower taper (eg, over 4 weeks) include history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).

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 a monoamine oxidase inhibitor (MAOI). A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between 2 selective serotonin reuptake inhibitors), 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 (Ref).

Switching to or from a monoamine oxidase inhibitor:

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

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

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, hepatically metabolized; use with caution. Some experts recommended reducing initial and maintenance doses by 50% in patients with hepatic impairment, with cautious dose adjustments based on response and tolerability up to 150 mg/day (Ref).

Dosing: Older Adult

Note: Avoid use (Ref).

Major depressive disorder (unipolar): Oral: Initial dose: Start at a lower dosage level (eg, 10 to 25 mg/day) and increase based on tolerance and response to a usual maximum of 100 mg/day; usual maintenance dose: 25 to 100 mg once daily or in divided doses; doses up to 150 mg/day may be necessary in severely depressed patients (maximum: 150 mg/day) (Ref).

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Desipramine: Pediatric drug information")

Attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD): Limited data available, dosing regimens variable: Titrate dose based on tolerance and response.

Note: Desipramine is not suggested as a therapeutic option in routine management (Ref); use should be reserved for patients who have failed or are unable to tolerate first- or second-line treatment options; may be beneficial for patients with comorbid conditions (eg, Tourette syndrome, depression, anxiety) (Ref).

Weight-directed dosing: Children ≥5 years and Adolescents: Oral: Initial: 1 to 1.5 mg/kg/day divided twice daily; titrate weekly up to target dose of 3.5 mg/kg/day in 2 divided doses by week 3 (Ref). A double-blind, placebo-controlled, parallel trial (n=41, treatment group: n=21) reported a significant reduction in core ADHD symptoms at mean desipramine dose of 3.4 mg/kg/day; however, a small but statistically significant increase in blood pressure and heart rate were observed in the treatment group (Ref).

Fixed dose:

Children ≥7 years and Adolescents ≤13 years: Oral: Initial: 25 mg at bedtime; increase at weekly intervals in 25 mg/day increments up to a maximum dose of 25 mg four times daily (100 mg/day) not to exceed 3 mg/kg/day (Ref).

Adolescents >13 years: Oral: Initial: 25 mg at bedtime; increase at weekly intervals in 25 mg/day increments to a maximum daily dose of 100 mg/day; usual dose range is 25 to 100 mg/day; dosing based on experience in younger patients with ADHD (Ref); in more severely ill patients, dose may be further increased to 150 mg/day; doses above 150 mg/day are not recommended (Ref).

Depression

Depression:

Note: Controlled clinical trials have not shown tricyclic antidepressants to be superior to placebo for the treatment of depression in children and adolescents. In the management of depression in children and adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, a selective serotonin reuptake inhibitor (SSRI) is recommended first line; desipramine is not a suggested therapeutic option; may be beneficial for patients with comorbid conditions or those who have failed first- and second-line treatment options (Ref).

Children 6 to 12 years: Limited data available: Oral: 1 to 3 mg/kg/day in divided doses; monitor carefully with doses >3 mg/kg/day; maximum daily dose: 5 mg/kg/day (Ref).

Adolescents: Oral: Initial dose: Start at the lower range and increase based on tolerance and response; usual maintenance dose: 25 to 100 mg/day divided up to 4 times/day; doses up to 150 mg/day may be necessary in severely depressed patients. Maximum daily dose: 150 mg/day.

Discontinuation of therapy: Consider planning antidepressant discontinuation for lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to antidepressant discontinuation (Ref). Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission 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 avoiding abrupt discontinuation of the medication to prevent withdrawal effects. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (Ref).

Switching antidepressants: Evidence for ideal antidepressant switching strategies in pediatric patients is sparse; strategies described in pediatric guidelines include a conservative approach (tapering and discontinuing the first selective serotonin reuptake inhibitor (SSRI) before adding the second) and cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant). While consensus does not exist regarding which approach to utilize, it is important to note that the conservative approach runs the risk for exacerbation of symptoms or discontinuation syndrome; cross-titration may avoid these risks but may increase the risk for the development of adverse effects or serotonin syndrome (Ref). 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 a monoamine oxidase inhibitor. While not as common of a strategy, a direct switch may be considered when switching to another agent in the same or similar class (eg, when switching between 2 SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects such as increased suicidal thoughts and behaviors or worsening depression or mania. 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 (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Adult HD/PD patients do not require supplemental doses.

Dosing: Liver Impairment: Pediatric

Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, hepatically metabolized; use with caution. In adult patients, reduced doses are suggested.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified. Some reactions listed are based on reports for other agents in this same pharmacologic class, and may not be specifically reported for desipramine.

Frequency not defined:

Cardiovascular: Acute myocardial infarction, cardiac arrhythmia, flushing, heart block, hypertension, hypotension, palpitations, tachycardia, ventricular fibrillation, ventricular premature contractions, ventricular tachycardia

Dermatologic: Alopecia, diaphoresis, pruritus, skin photosensitivity, skin rash, urticaria

Endocrine & metabolic: Decreased libido, decreased serum glucose, galactorrhea not associated with childbirth, gynecomastia, increased libido, increased serum glucose, SIADH, weight gain, weight loss

Gastrointestinal: Abdominal cramps, anorexia, constipation, diarrhea, dysgeusia, epigastric distress, increased pancreatic enzymes, melanoglossia, nausea, paralytic ileus, parotid gland enlargement, stomatitis, sublingual adenitis, vomiting, xerostomia

Genitourinary: Breast hypertrophy, impotence, nocturia, painful ejaculation, testicular swelling, urinary frequency, urinary hesitancy, urinary retention, urinary tract dilation

Hematologic & oncologic: Agranulocytosis, petechia, purpuric disease, thrombocytopenia

Hypersensitivity: Allergic angioedema, facial edema, tongue edema

Nervous system: Agitation, anxiety, asthenia, ataxia, cerebrovascular accident, confusion, delusion, disorientation, dizziness, drowsiness, EEG pattern changes, extrapyramidal reaction, falling, fatigue, hallucination, headache, hypomania, insomnia, nightmares, numbness, peripheral neuropathy, peripheral paresthesia, psychosis (exacerbation), restlessness, seizure, serotonin syndrome, suicidal ideation, suicidal tendencies, tingling sensation, tremor, withdrawal syndrome

Ophthalmic: Accommodation disturbance, blurred vision, increased intraocular pressure, mydriasis

Otic: Tinnitus

Miscellaneous: Drug fever, fever

Postmarketing:

Hematologic & oncologic: Eosinophilia (Price 1983)

Hepatic: Abnormal liver function (including hepatitis, increased liver enzymes [increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase]) (Price 1983), hepatic necrosis (Powell 1968), jaundice (including obstructive jaundice) (Powell 1968)

Nervous system: Neuroleptic malignant syndrome (Baca 1990), stuttering (Masand 1992), uncontrolled and repetitive jaw movements (jaw myoclonus) (Masand 1992)

Contraindications

Hypersensitivity to desipramine or any component of the formulation; use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders (concurrently or within 14 days of stopping desipramine or an MAOI); initiation of desipramine in a patient receiving IV methylene blue; use in a patient during the acute recovery phase of myocardial infarction.

Note: Although desipramine is contraindicated per manufacturer labeling when used in combination with linezolid, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore these agents can be administered concomitantly when necessary. Monitor patients on this combination; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in the US labeling): Uncontrolled cardiac decompensation.

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 healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Desipramine is FDA approved for the treatment of depression in adolescents.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. 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:

• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with extreme caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is low relative to other antidepressants (APA, 2010).

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating 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).

• Hematologic effects: TCAs may rarely cause bone marrow suppression; monitor for any signs of infection and obtain CBC if symptoms (eg, fever, sore throat) evident.

• 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.

• Orthostatic hypotension: May cause orthostatic hypotension (risk is moderate relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia) (APA, 2010).

• 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, monoamine oxidase inhibitors [MAOIs] intended to treat psychiatric disorders and other MAOIs, including IV 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.

• SIADH and hyponatremia: Antidepressant agents have been associated with the development of SIADH and hyponatremia, predominately in elderly patients. Other risk factors include volume depletion, concurrent use of diuretics, female gender, low body weight, and severe physical illness. TCAs have a lower risk for hyponatremia in comparison to SSRIs (De Picker 2014).

Disease-related concerns:

• Cardiovascular disease: Due to risk of conduction abnormalities, use with extreme caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities) or in patients with a family history of sudden death, dysrhythmias, or conduction abnormalities.

• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose regulation (APA, 2010).

• Hepatic impairment: Use with caution in patients with hepatic impairment; half-life may be increased. Due to the narrow therapeutic index, use lower initial and maintenance doses of tricyclic antidepressants. Use caution in patients with hepatic encephalopathy due to the risk of neurocognitive effects (Mauri 2014; Mullish 2014).

• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer should also be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Desipramine is not FDA approved for the treatment of bipolar depression.

• Renal impairment: Use with caution in patients with renal impairment.

• Seizure disorder: Use with extreme caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. In some patients, seizures may precede cardiac dysrhythmias and death.

Special populations:

• Older adult: May increase risk of falling or confusional states.

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, lightheadedness, 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: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.

• Surgery: Recommended by the manufacturer to discontinue prior to elective surgery; risks exist for drug interactions with anesthesia and for cardiac arrhythmias. However, some experts recommend continuing tricyclic antidepressants prior to surgery (Pass 2004). Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.

Warnings: Additional Pediatric Considerations

The AAP and AHA recommend clinicians carefully assess all children for cardiac abnormalities, including those whom attention-deficit/hyperactivity disorder (ADHD) treatment is being considered. This includes assessment using history and physical assessments. An ECG should be considered but is not mandatory and treatment should not be withheld if an ECG cannot be obtained. Medications used to treat ADHD may increase or decrease blood pressure and heart rate and should be monitored routinely although these effects are not considered dangerous. These effects should be more closely monitored in children and adolescents with heart conditions as determined by the clinician (AHA [Vetter 2008]).

Asymptomatic ECG changes and minor increases in diastolic blood pressure and heart rate have been noted in children receiving desipramine doses >3.5 mg/kg/day; 4 cases of sudden death have been reported in children and adolescents 5 to 14 years of age; an association between desipramine and sudden death was not observed in one retrospective study. Pretreatment cardiovascular assessment should include a combination of thorough medical history, family history, and physical examination. An ECG is not mandatory but should be considered.

Dosage Forms: US

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

Tablet, Oral, as hydrochloride:

Norpramin: 10 mg [contains corn starch, fd&c blue #1 (brilliant blue), sodium benzoate, soybean oil]

Norpramin: 25 mg [contains corn starch, quinoline yellow (d&c yellow #10), sodium benzoate, soybean oil]

Generic: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Desipramine HCl Oral)

10 mg (per each): $1.18 - $1.67

25 mg (per each): $1.42 - $2.00

50 mg (per each): $2.68 - $3.77

75 mg (per each): $3.10 - $4.80

100 mg (per each): $4.48 - $6.31

150 mg (per each): $6.49 - $9.15

Tablets (Norpramin Oral)

10 mg (per each): $1.86

25 mg (per each): $2.23

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.

Dosage Forms: Canada

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

Tablet, Oral, as hydrochloride:

Generic: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

Administration: Pediatric

Oral: Administer with food to decrease GI upset.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/014399s066s067mg.pdf, must be dispensed with this medication.

Use: Labeled Indications

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

Use: Off-Label: Adult

Diabetic neuropathy; Functional dyspepsia; Irritable bowel syndrome–associated pain and global symptoms; Postherpetic neuralgia

Medication Safety Issues
Sound-alike/look-alike issues:

Desipramine may be confused with clomiPRAMINE, dalfampridine, diphenhydrAMINE, disopyramide, imipramine, nortriptyline

Norpramin may be confused with clomiPRAMINE, imipramine, Normodyne, Norpace, nortriptyline, Tenormin

Older Adult: High-Risk Medication:

Desipramine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its strong anticholinergic properties and potential for sedation and orthostatic hypotension. In addition, use TCAs with caution due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2023]).

Pediatric patients: High-risk medication:

KIDs List: Desipramine, when used in pediatric patients <18 years of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of sudden cardiac death (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).

International issues:

Norpramin: Brand name for desipramine [U.S., Canada], but also the brand name for enalapril/hydrochlorothiazide [Portugal]; omeprazole [Spain]

Metabolism/Transport Effects

Substrate of CYP1A2 (Minor), CYP2D6 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor

Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Agents with Clinically Relevant Anticholinergic Effects: May increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor

Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor

Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Almotriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Alosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Alpha-/Beta-Agonists: Tricyclic Antidepressants may increase vasopressor effects of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Risk D: Consider Therapy Modification

Alpha1-Agonists: Tricyclic Antidepressants may increase therapeutic effects of Alpha1-Agonists. Tricyclic Antidepressants may decrease therapeutic effects of Alpha1-Agonists. Risk C: Monitor

Alpha2-Agonists (Ophthalmic): Tricyclic Antidepressants may decrease therapeutic effects of Alpha2-Agonists (Ophthalmic). Risk C: Monitor

Alpha2-Agonists: Tricyclic Antidepressants may decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Risk D: Consider Therapy Modification

Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor

Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amphetamines: Tricyclic Antidepressants may increase adverse/toxic effects of Amphetamines. Tricyclic Antidepressants may potentiate the cardiovascular effects of Amphetamines. Amphetamines may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased cardiovascular effects when these agents are combined. Risk C: Monitor

Antiemetics (5HT3 Antagonists): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor

ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Baclofen: Tricyclic Antidepressants may increase adverse neuromuscular effects of Baclofen. Baclofen may increase CNS depressant effects of Tricyclic Antidepressants. Risk C: Monitor

Barbiturates: May increase metabolism of Tricyclic Antidepressants. Management: Monitor for decreased efficacy of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. Tricyclic antidepressant dose adjustments are likely required. Risk D: Consider Therapy Modification

Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor

Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor

Beta-Acetyldigoxin: Tricyclic Antidepressants may increase arrhythmogenic effects of Beta-Acetyldigoxin. Risk C: Monitor

Beta2-Agonists: Tricyclic Antidepressants may increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor

Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor

Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor

Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromopride: May increase adverse/toxic effects of Tricyclic Antidepressants. Risk X: Avoid

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification

BuPROPion: Tricyclic Antidepressants may increase neuroexcitatory and/or seizure-potentiating effects of BuPROPion. BuPROPion may increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

BusPIRone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

CarBAMazepine: May decrease serum concentration of Tricyclic Antidepressants. Risk C: Monitor

Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Chlorprothixene: May increase QTc-prolonging effects of Tricyclic Antidepressants. Risk X: Avoid

Cimetidine: May increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor

Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid

Citalopram: Tricyclic Antidepressants may increase serotonergic effects of Citalopram. Tricyclic Antidepressants may increase serum concentration of Citalopram. Citalopram may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA and citalopram concentrations/effects. Risk C: Monitor

Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider Therapy Modification

CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Cocaine (Topical): May increase adverse/toxic effects of Tricyclic Antidepressants. Risk C: Monitor

Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Cyclobenzaprine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

CYP2D6 Inhibitors (Moderate): May increase serum concentration of Desipramine. Risk C: Monitor

CYP2D6 Inhibitors (Strong): May increase serum concentration of Desipramine. Risk C: Monitor

Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dapoxetine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid

Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor

Desmopressin: Tricyclic Antidepressants may increase hyponatremic effects of Desmopressin. Risk C: Monitor

DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification

Dexmethylphenidate-Methylphenidate: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Dextromethorphan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor

DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid

Dronedarone: Tricyclic Antidepressants may increase arrhythmogenic effects of Dronedarone. Risk X: Avoid

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

DULoxetine: May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. DULoxetine may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations and effects if these agents are combined. Risk C: Monitor

Eletriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Epinephrine (Racemic): Tricyclic Antidepressants may increase adverse/toxic effects of Epinephrine (Racemic). Risk X: Avoid

Ergot Derivatives: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Escitalopram: Tricyclic Antidepressants may increase serotonergic effects of Escitalopram. Escitalopram may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor

Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Fenfluramine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor

Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification

FLUoxetine: May increase serotonergic effects of Tricyclic Antidepressants. FLUoxetine may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider Therapy Modification

Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor

FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

FluvoxaMINE: May increase serotonergic effects of Tricyclic Antidepressants. FluvoxaMINE may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor

Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor

Gepirone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor

Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor

Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid

Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor

Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Guanethidine: Tricyclic Antidepressants may decrease therapeutic effects of Guanethidine. Risk C: Monitor

Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor

HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification

Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Iobenguane Radiopharmaceutical Products: Tricyclic Antidepressants may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid

Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor

Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lasmiditan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid

Linezolid: May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofexidine: Tricyclic Antidepressants may decrease therapeutic effects of Lofexidine. Management: Consider avoiding this drug combination when possible. If concurrent administration is required, monitor blood pressure carefully at the beginning of the combined therapy and when either drug is stopped. Adjust the dosage accordingly. Risk D: Consider Therapy Modification

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor

Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid

Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Melperone: Tricyclic Antidepressants may increase adverse/toxic effects of Melperone. Melperone may increase adverse/toxic effects of Tricyclic Antidepressants. Melperone may increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metaxalone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification

Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor

Methylene Blue: Tricyclic Antidepressants may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metoclopramide: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor

Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Monoamine Oxidase Inhibitors (Antidepressant): May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nefazodone: Tricyclic Antidepressants may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Nicorandil: Tricyclic Antidepressants may increase hypotensive effects of Nicorandil. Risk C: Monitor

Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: Tricyclic Antidepressants may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Tricyclic Antidepressants may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Risk C: Monitor

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor

OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Ondansetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opipramol: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification

OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor

OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

PARoxetine: May increase serotonergic effects of Tricyclic Antidepressants. PARoxetine may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider Therapy Modification

Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor

Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor

Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pitolisant: Tricyclic Antidepressants may decrease therapeutic effects of Pitolisant. Risk X: Avoid

Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor

Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid

Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor

Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor

Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest 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

QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor

Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor

Ramosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Rasagiline: May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid

Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid

RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification

ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Safinamide: May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid

Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor

Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider Therapy Modification

Selegiline: May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid

Serotonergic Agents (High Risk, Miscellaneous): Tricyclic Antidepressants may increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Serotonergic Non-Opioid CNS Depressants: Tricyclic Antidepressants may increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Tricyclic Antidepressants may increase CNS depressant effects of Serotonergic Non-Opioid CNS Depressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and CNS depression when these agents are combined. Risk C: Monitor

Serotonergic Opioids (High Risk): May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Tricyclic Antidepressants may increase CNS depressant effects of Serotonergic Opioids (High Risk). Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity and CNS depression. Risk D: Consider Therapy Modification

Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Serotonin/Norepinephrine Reuptake Inhibitor: May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes when these agents are combined. Risk C: Monitor

Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Sertraline: May increase serotonergic effects of Tricyclic Antidepressants. Sertraline may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor

Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid

St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor

Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Syrian Rue: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor

Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor

Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor

Thyroid Products: May increase arrhythmogenic effects of Tricyclic Antidepressants. Thyroid Products may increase stimulatory effects of Tricyclic Antidepressants. Risk C: Monitor

Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor

Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid

Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor

Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor

Tricyclic Antidepressants: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor

Tricyclic Antidepressants: May increase anticholinergic effects of Tricyclic Antidepressants. Tricyclic Antidepressants may increase CNS depressant effects of Tricyclic Antidepressants. Tricyclic Antidepressants may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor closely for increased TCA adverse effects, including serotonin syndrome/serotonin toxicity, CNS depression, and anticholinergic effects. Risk C: Monitor

Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor

Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor

Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Valproic Acid and Derivatives: May increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor

Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor

Vilazodone: Tricyclic Antidepressants may increase serotonergic effects of Vilazodone. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor

Vortioxetine: Tricyclic Antidepressants may increase serotonergic effects of Vortioxetine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor

Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Ziprasidone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor

Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification

Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor

Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification

Reproductive Considerations

Evaluate pregnancy status prior to initiating treatment for depression in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of antidepressant response (ACOG 2023; WFSBP [Dodd 2018]). When treating depression, tricyclic antidepressants are not first-line medications for use prior to conception in patients who are treatment naïve or who do not have a history of effective treatment. Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]).

Pregnancy Considerations

Outcome data following maternal use of tricyclic antidepressants (TCAs), including desipramine, during pregnancy are available (Altshuler 1996; Bérard 2017; Cantarutti 2017; De Vries 2021; Huybrechts 2015; McDonagh 2014; McElhatton 1996). Study outcomes vary due to limited data, differences in study design, and confounders (Gentile 2014; Yonkers 2014).

The pharmacokinetics of desipramine may be influenced by pregnancy. Data are not available to make recommendation, however, therapeutic drug monitoring of TCAs can be considered during pregnancy and postpartum to avoid toxicity and monitor efficacy (Deligiannidis 2014).

Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated or undertreated depression is associated with preterm birth, low birth weight, preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Discontinuing effective medications during pregnancy increases the risk of relapse. Management of mental health conditions should be made as part of a shared decision-making process (ACOG 2023). Patients effectively treated for depression prepregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023). TCAs are not considered first-line medications for pregnant patients who are treatment naïve or who do not have a history of effective treatment with another medication (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]), but may be considered as an alternative (CANMAT [MacQueen 2016]). When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Close monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).

Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Encourage pregnant patients 45 years of age and younger with a history of psychiatric illness to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants).

Breastfeeding Considerations

Desipramine and the metabolite 2-hydroxydesipramine are present in breast milk.

• Data related to the presence of desipramine in breast milk are available from a lactating patient following administration of desipramine 300 mg daily at 11pm. Breast milk was sampled after 1 week of therapy (~10 weeks postpartum). Breast milk concentrations of desipramine and 2-hydroxydesipramine were 316 ng/mL and 381 ng/mL, respectively, at 8 am on day 7 of therapy. On day 14, samples collected at 9:20 am contained desipramine 328 ng/mL and 2-hydroxydesipramine 327 ng/mL. Infant plasma concentrations of desipramine and the metabolite were <1 ng/mL and <5 ng/mL, respectively, on both days. Maternal plasma levels were ~30% less than breast milk concentrations. Toxicity was not observed in the breastfed infant (Stancer 1986).

• Desipramine and 2-hydroxydesipramine were not present in the serum of four breastfed infants following maternal use of desipramine. Among the four mother/infant pairs, the highest dose of desipramine was 200 mg/day taken by one mother during the third trimester and postpartum. The infant was tested twice (at 2.3 and 14.9 weeks of age) and was breastfed 7 to 9 times/day. At both time periods the infant serum concentration of desipramine was <25 ng/mL. The oldest infant was 33.1 weeks at the time of testing. The mother initiated desipramine 37 mg/day postpartum and breastfed 0 to 3 times/day. Infant serum concentrations of desipramine were <10 ng/mL (Birnbaum 1999).

Monitor infants exposed to psychotropic medication via breast milk for adverse effects (eg, over sedation, poor feeding) (BAP [McAllister-Williams 2017]).

Patients effectively treated for depression with a tricyclic antidepressant (TCA) during pregnancy may continue their medication postpartum unless contraindications to breastfeeding exist. The presence and concentration of the drug in breast milk, efficacy of maternal treatment, and infant age should be considered when initiating a medication for the first time postpartum. When first initiating an antidepressant in a patient who is treatment naïve and breastfeeding, agents other than TCAs are preferred (ABM [Sriraman 2015]), but may be considered as an alternative (CANMAT [MacQueen 2016]).

Monitoring Parameters

Serum sodium in at-risk populations (as clinically indicated) (DePicker 2014); CBC; blood glucose; electrolyte panel (to assess risk of conduction abnormalities); blood levels are useful for therapeutic monitoring; vitals (baseline and during initial therapy); mental status; symptoms of depression, clinical worsening, suicidality, psychosis, or unusual changes in behavior (such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, and social functioning), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increased or decreases); weight, BMI; ECG (older adults and those with cardiac disease).

When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, BP, and consider obtaining ECG prior to initiation (Vetter 2008); ensure PR interval ≤200 ms, QRS duration ≤120 ms, and QTc ≤460 ms.

Reference Range

Timing of serum samples: Draw trough just before next dose.

Therapeutic reference range: 100 to 300 ng/mL (SI: 375 to 1,125 nmol/L).

Laboratory alert level: 300 ng/mL (SI: 1,125 nmol/L) (Hiemke 2018).

Mechanism of Action

Traditionally believed to increase the synaptic concentration of norepinephrine (and to a lesser extent, serotonin) in the central nervous system by inhibition of its reuptake by the presynaptic neuronal membrane. However, additional receptor effects have been found including desensitization of adenyl cyclase, down regulation of beta-adrenergic receptors, and down regulation of serotonin receptors.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009).

Absorption: Rapid

Metabolism: Hepatic

Bioavailability: 38% (Hiemke 2018)

Half-life elimination: Adults: 15 to 24 hours (Weiner 1981)

Time to peak, plasma: ~6 hours (Weiner 1981)

Excretion: Urine (~70%)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Older adult: The ratio of 2-hydroxydesipramine to desipramine may be elevated due to decreased renal elimination with aging.

Cigarette smoking: Tricyclic antidepressant plasma levels are reduced due to induced liver enzyme activity.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Norpramin;
  • (AR) Argentina: Nebril;
  • (AT) Austria: Pertofran;
  • (AU) Australia: Pertofran;
  • (BE) Belgium: Pertofran;
  • (CH) Switzerland: Pertofran;
  • (CL) Chile: Distonal;
  • (CZ) Czech Republic: Petylyl;
  • (DE) Germany: Pertofran | Petylyl;
  • (DO) Dominican Republic: Desipramina | Nortimil;
  • (FI) Finland: Pertofran;
  • (FR) France: Pertofran;
  • (GB) United Kingdom: Pertofran;
  • (IL) Israel: Deprexan;
  • (IT) Italy: Nortimil;
  • (KR) Korea, Republic of: Desipramine;
  • (LT) Lithuania: Petylyl;
  • (LU) Luxembourg: Pertofran;
  • (LV) Latvia: Petylyl;
  • (NL) Netherlands: Pertofran;
  • (NZ) New Zealand: Pertofran;
  • (PL) Poland: Nortimil | Pertofran | Petylyl;
  • (PR) Puerto Rico: Desipramine HCL | Norpramin;
  • (SE) Sweden: Pertofrin;
  • (TN) Tunisia: Pertofran;
  • (TW) Taiwan: Desipramine | Norpramin
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