(im IP ra meen)
Childhood enuresis: As temporary adjunctive therapy in reducing enuresis in children ≥6 years of age, after possible organic causes have been excluded by appropriate tests
Depression: Treatment of depression
Hypersensitivity to imipramine (cross-reactivity with other dibenzodiazepines may occur) or any component of the formulation; in a patient during acute recovery phase of MI; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either imipramine or the MAO inhibitor); initiation of imipramine in a patient receiving linezolid or intravenous methylene blue
Antidepressants increased the risk compared with placebo of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of imipramine 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. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the health care provider. Imipramine is not approved for use in pediatric patients except for patients with nocturnal enuresis.
Depression: Oral:
Outpatients: Initial: 75 mg daily; may increase gradually to 150 mg daily. May be given in divided doses or as a single bedtime dose; Maintenance 50-150 mg daily; maximum: 200 mg daily
Inpatients: Initial: 100-150 mg daily; may increase gradually to 200 mg daily; if no response after 2 weeks, may further increase to 250-300 mg daily. May be given in divided doses or as a single bedtime dose; maximum: 300 mg daily.
Bulimia nervosa (off-label use): Oral: Initial: 50 mg at bedtime; increase gradually based on response and tolerability up to 300 mg at bedtime (Agras 1987; Mitchell 1990; Pope 1983).
Neuropathic pain (off-label use): Oral: Note: Not the preferred TCA (Bril 2011; Dworkin 2007). Initial: 50 mg once daily or in divided doses twice daily; increase gradually up to 150 mg daily (Kvinesdal 1984; Sindrup 2003) or to a dosage sufficient to achieve an imipramine plus desipramine plasma concentration of 113-170 ng/mL (SI: 400-600 nmol/L) (Sindrup 1989; Sindrup 1990)
Panic disorder (off-label use): Oral: Initial: 10 mg once daily; increase gradually to a usual dose of 75-300 mg daily (APA 2009; Bandelow 2008)
Post-traumatic stress disorder (PTSD) (off-label use): Oral: Initial: 50 mg once daily; increase gradually to 200-300 mg once daily to achieve blood levels in the therapeutic range (>150 ng/mL) (Frank 1988; Kosten 1991)
Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddod 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).
MAO inhibitor recommendations:
Switching to or from an MAO inhibitor intended to treat psychiatric disorders:
Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of imipramine.
Allow 14 days to elapse between discontinuing imipramine and initiation of an MAO inhibitor intended to treat psychiatric disorders.
Use with other MAO inhibitors (linezolid or IV methylene blue):
Do not initiate imipramine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition (Zyvox prescribing information; methylene blue prescribing information).
If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving imipramine and potential benefits outweigh potential risks, discontinue imipramine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume imipramine 24 hours after the last dose of linezolid or IV methylene blue.
Depression: Initial: 25-50 mg at bedtime; may increase every 3 days for inpatients and weekly for outpatients if tolerated to a recommended maximum of 100 mg daily
Discontinuation of therapy: Refer to adult dosing.
MAO inhibitor recommendations: Refer to adult dosing.
Note: Manufacturer labeling warns against use of doses >2.5 mg/kg/day in pediatric patients; ECG changes (of unknown significance) have been reported in pediatric patients who received twice this amount.
Depression: Adolescents: Oral: Initial: 25 to 50 mg daily; increase gradually; maximum: 100 mg daily in single or divided doses. Note: Controlled clinical trials have not shown tricyclic antidepressants to be superior to placebo for the treatment of depression in children and adolescents; not recommended as first-line medication; may be beneficial for patient with comorbid conditions (ADHD, enuresis) (Birmaher 2007; Dopheide 2006; Wagner 2005).
Enuresis: Imipramine hydrochloride: Children ≥6 years and Adolescents: Oral: Initial: 10 to 25 mg 1 hour before bedtime (Kliegman 2007), if inadequate response still seen after 1 week of therapy, increase by 25 mg daily; dose should not exceed 2.5 mg/kg/day or 50 mg at bedtime if 6 to 12 years or 75 mg at bedtime if ≥12 years.
Attention-deficit/hyperactivity disorder (off-label use): Children ≥6 years and Adolescents: Oral: Initial: 1 mg/kg/day in 1 to 3 divided doses; titrate as needed; maximum daily dose: 4 mg/kg/day or 200 mg daily; for doses >2 mg/kg/day, monitor serum concentrations (target: ≤200 ng/mL) (Himpel 2005; Pliszka 2007).
Discontinuation of therapy: Refer to adult dosing.
MAO inhibitor recommendations: Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer 's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer 's labeling; use with caution.
Capsules, tablets: Store between 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as pamoate:
Tofranil-PM: 75 mg [DSC], 100 mg [DSC], 125 mg [DSC], 150 mg [DSC]
Generic: 75 mg, 100 mg, 125 mg, 150 mg
Tablet, Oral, as hydrochloride:
Tofranil: 10 mg, 25 mg, 50 mg
Generic: 10 mg, 25 mg, 50 mg
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Management: Avoid, if possible, the use of direct-acting 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. Exceptions: Dipivefrin. Consider therapy modification
Alpha1-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the vasopressor effect of Alpha1-Agonists. Monitor therapy
Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine (Ophthalmic). Consider therapy modification
Alpha2-Agonists (Ophthalmic): Tricyclic Antidepressants may diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Monitor therapy
Altretamine: May enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Monitor therapy
Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Aspirin: Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of Aspirin. Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Consider therapy modification
Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
BuPROPion: May decrease the metabolism of Tricyclic Antidepressants. Management: Seek alternatives when possible. Monitor patients receiving these combinations closely for increased serum concentrations (when testing is available) and toxic effects of the tricyclic antidepressant. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cimetidine: May decrease the metabolism of Tricyclic Antidepressants. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Management: Seek alternatives when possible. If these combinations are used, monitor closely for increased effects/toxicity and/or elevated serum concentrations (when testing is available) of the tricyclic antidepressant. Consider therapy modification
Citalopram: Tricyclic Antidepressants may enhance the adverse/toxic effect of Citalopram. Tricyclic Antidepressants may increase the serum concentration of Citalopram. Citalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with citalopram. Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates. Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Desmopressin: Tricyclic Antidepressants may enhance the adverse/toxic effect of Desmopressin. Monitor therapy
Dexmethylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Dexmethylphenidate may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Dronedarone: Tricyclic Antidepressants may enhance the arrhythmogenic effect of Dronedarone. Avoid combination
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
DULoxetine: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. DULoxetine may decrease the metabolism of Tricyclic Antidepressants. Management: Use these drugs in combination with caution. Monitor closely for signs and symptoms of serotonin toxicity/serotonin syndrome. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates. Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification
Escitalopram: Tricyclic Antidepressants may enhance the adverse/toxic effect of Escitalopram. Escitalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with escitalopram. Consider therapy modification
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
FLUoxetine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. FLUoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluoxetine. Consider therapy modification
FluvoxaMINE: May enhance the adverse/toxic effect of Tricyclic Antidepressants. FluvoxaMINE may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluvoxamine. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Iobenguane I 123: Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane I 123. Avoid combination
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Linezolid: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Avoid combination
Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP2C19 Substrates. Monitor therapy
Lumacaftor: May decrease the serum concentration of CYP2C19 Substrates. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
Methylene Blue: Tricyclic Antidepressants may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Methylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy
Metoclopramide: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with tricyclic antidepressants for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
MetyroSINE: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Moxonidine: Tricyclic Antidepressants may diminish the therapeutic effect of Moxonidine. Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: Tricyclic Antidepressants may enhance the hypotensive effect of Nicorandil. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
NSAID (COX-2 Inhibitor): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Monitor therapy
NSAID (Nonselective): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
PARoxetine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with paroxetine. Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Protease Inhibitors: May increase the serum concentration of Tricyclic Antidepressants. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
QuiNIDine: Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy
Sertraline: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Sertraline may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with sertraline. Consider therapy modification
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Sodium Phosphates: Tricyclic Antidepressants may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure and/or loss of consciousness may be increased in patients with significant sodium phosphate induced fluid/electrolyte abnormalities. Monitor therapy
St Johns Wort: May increase the metabolism of Tricyclic Antidepressants. The risk of serotonin syndrome may theoretically be increased. Consider therapy modification
Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect 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. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Terbinafine (Systemic): May increase the serum concentration of Imipramine. Management: Monitor for increased effects/toxicity of imipramine during concomitant administration with terbinafine. Reduced dosages of imipramine may be needed. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Thyroid Products: May enhance the arrhythmogenic effect of Tricyclic Antidepressants. Thyroid Products may enhance the stimulatory effect of Tricyclic Antidepressants. Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Valproate Products: May increase the serum concentration of Tricyclic Antidepressants. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Tricyclic Antidepressants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Yohimbine: Tricyclic Antidepressants may increase the serum concentration of Yohimbine. Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect 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. Consider therapy modification
CBC, ECG (baseline and with dose increases) in older adults, with high doses, and/or in patients with pre-existing cardiovascular disease; monitor blood pressure and pulse rate prior to and during initial therapy; evaluate mental status, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased); anxiety, social functioning, panic attacks; signs/symptoms of serotonin syndrome; blood glucose; weight and BMI; blood levels are useful for therapeutic monitoring (APA 2010; Perrin 2008; Pliszka 2007; Vetter 2008)
Reported for tricyclic antidepressants in general. Frequency not defined.
Cardiovascular: Cardiac arrhythmia, cardiac failure, cerebrovascular accident, ECG changes, heart block, hypertension, myocardial infarction, orthostatic hypotension, palpitations, tachycardia
Central nervous system: Agitation, anxiety, ataxia, confusion, delusions, disorientation, dizziness, drowsiness, EEG pattern changes, extrapyramidal reaction, falling, fatigue, hallucination, headache, hypomania, insomnia, nightmares, numbness, paresthesia, peripheral neuropathy, psychosis, restlessness, seizure, taste disorder, tingling sensation
Dermatologic: Alopecia, diaphoresis, pruritus, skin photosensitivity, skin rash, urticaria
Endocrine & metabolic: Decreased libido, decreased serum glucose, galactorrhea, gynecomastia, increased libido, increased serum glucose, SIADH, weight gain, weight loss
Gastrointestinal: Abdominal cramps, anorexia, constipation, diarrhea, epigastric distress, intestinal obstruction, melanoglossia, nausea, stomatitis, sublingual adenitis, vomiting, xerostomia
Genitourinary: Breast hypertrophy, impotence, testicular swelling, urinary hesitancy, urinary retention, urinary tract dilation
Hematologic & oncologic: Agranulocytosis, eosinophilia, petechia, purpura, thrombocytopenia
Hepatic: Cholestatic jaundice, increased serum transaminases
Hypersensitivity: Hypersensitivity (eg, drug fever, edema)
Neuromuscular & skeletal: Tremor, weakness
Ophthalmic: Accommodation disturbance, angle-closure glaucoma, blurred vision, mydriasis
Otic: Tinnitus
Decreased clearance of imipramine and an increased elimination half-life may occur in elderly patients (Sallee 1990)
Alcohol use disorder: Increased clearance of imipramine and a decreased elimination half-life may occur in patients with alcohol use disorder
Cigarette smoking: Lower steady-state levels of imipramine and increased metabolism may occur in smokers (Sallee 1990)
Major psychiatric warnings:
- Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient 's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Imipramine is FDA approved for the treatment of nocturnal enuresis in children ≥6 years of age.
- 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 patients 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 caution in patients with decreased gastrointestinal motility, increased intraocular pressure, angle-closure glaucoma, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is high relative to other antidepressants.
- 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. Discontinue imipramine if there is evidence of pathological neutrophil depression.
- Orthostatic hypotension: May cause orthostatic hypotension (risk is very high 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).
- Photosensitization: Has been associated with photosensitization; avoid excessive exposure to sunlight.
- Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is high relative to other antidepressants.
- Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John 's wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.
Disease-related concerns:
- Alcohol use disorder: Pharmacokinetics of imipramine may be altered in patients with chronic alcohol use disorder; increased clearance and a decreased elimination half-life have been reported (Sallee 1990).
- Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk of conduction abnormalities with this agent is high relative to other antidepressants.
- Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose regulation.
- Hepatic impairment: Use with caution in patients with hepatic impairment.
- Mania/hypomania: May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Imipramine is not FDA approved for the treatment of bipolar depression.
- 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.
- Renal impairment: Use with caution in patients with renal impairment.
- Seizure disorder: Use with 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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Children: A dose of 2.5 mg/kg/day of imipramine hydrochloride should not be exceeded in childhood. ECG changes of unknown significance have been reported in pediatric patients with doses twice this amount.
- Elderly: Lower doses may be required in geriatric patients due to pharmacokinetic changes.
- Smokers: Imipramine levels may be lower in patients who smoke (Sallee 1990).
Other warnings/precautions:
- Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddod 2001; Shelton 2001; Warner 2006).
- ECG monitoring: Baseline and periodic assessment recommended with use of higher dosages; should also be considered in elderly patients and/or patients with pre-existing cardiovascular disease.
- 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, definitive drug interactions have not been widely reported in the literature and continuation of tricyclic antidepressants is generally recommended as long as precautions are taken to reduce the significance of any adverse events that may occur. Norepinephrine should be considered the vasopressor of choice for TCA-related hypotension (Pass 2004). Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
Animal reproduction studies are inconclusive. Congenital abnormalities have been reported in humans; however, a causal relationship has not been established. Tricyclic antidepressants may be associated with irritability, jitteriness, and convulsions (rare) in the neonate (Yonkers 2009). Due to pregnancy-induced physiologic changes, women who are pregnant may require dose adjustments late in pregnancy to achieve euthymia (Altshuler 1996).
The ACOG recommends that therapy for depression during pregnancy be individualized; treatment should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician (ACOG 2008). According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery (APA 2010). Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers 2009).
Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.
Traditionally believed to increase the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their 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.
Well absorbed; not effected by food (Sallee 1990)
Vd: Children: 14.5 L/kg; Adults: ~10-20 L/kg (Sallee 1990)
Hepatic, primarily via CYP2D6 to desipramine (active) and other metabolites; significant first-pass effect (Sallee 1990)
Urine (as metabolites; <5% unchanged) (Salle 1990)
Depression: Individual responses vary, however 4-8 weeks of treatment is needed before determining if a patient is partially or nonresponsive (APA 2010).
Serum: 2-6 hours (Sallee 1990)
8-21 hours (Salle 1990); Mean: Children: 11 hours; Adults: 16-17 hours; Desipramine (active metabolite): 22-28 hours
60% to 96%; primarily to alpha1 acid glycoprotein and lipoproteins; to a lesser extent albumin (Sallee 1990)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dry mouth, constipation, nausea, vomiting, or fatigue. Have patient report immediately to prescriber vision changes, eye pain, eye irritation, signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), severe dizziness, passing out, urinary retention, loss of strength and energy, insomnia, sexual dysfunction, decreased libido, chills, pharyngitis, jaundice, bruising, bleeding, angina, tachycardia, tinnitus, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, severe diarrhea) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.