QuickView for Trimipramine (compound)

Summary
General Info

PubChem

PubChem Compound 101726

Name:	Trimipramine
PubChem Compound ID:	101726
Description:	Tricyclic antidepressant similar to IMIPRAMINE, but with more antihistaminic and sedative properties.
Molecular formula:	C₁₁H₁₇N₃O₃
Molecular weight:	239.271 g/mol
Synonyms:	2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-ethyl-5-(1-piperidinyl)- (9CI); 5-Ethyl-5-piperidinobarbituric acid; Acide 5-ethyle 5'-piperidino barbiturique [French]; Eldoral heyden; Ethylpentamethyleneuramil; 509-87-5; Eldoral; BRN 0252400; 4-25-00-04239 (Beilstein Handbook Reference); Barbituric acid, 5-ethyl-5-piperidino-

DrugBank

Identification

Name:	Trimipramine
Name (isomeric):	DB00726
Drug Type:	small molecule
Description:	Tricyclic antidepressant similar to IMIPRAMINE, but with more antihistaminic and sedative properties.
Synonyms:	Trimipramina [INN-Spanish]; Trimeprimina [Italian]; Trimipraminum [INN-Latin]; beta-Methylimipramine; Trimeprimine
Brand:	Temaril, Surmontil, Surmontyl, Sapilent
Category:	Norepinephrine-Reuptake Inhibitors, Antidepressants, Adrenergic Uptake Inhibitors, Antidepressive Agents, Tricyclic
CAS number:	739-71-9

Pharmacology

Indication:	For the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance
Pharmacology:	Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the c... show more » Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic. show less «
Mechanism of Action:	Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).
Absorption:	Rapid absorption
Protein binding:	93%-96% (to plasma proteins)
Biotransformation:	Hepatic
Half Life:	11-18 hrs
Toxicity:	Side effects include agitation, coma, confusion, convulsions, dilated pupils, disturbed concentration, drowsiness, hallucinations, high fever, irregular heart rate, low body temperature, muscle rigidity, overactive reflexes, severely low blood pressure, stupor, vomiting
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Sertraline	The SSRI, Sertraline, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Sertraline is initiated, discontinued or dose changed.
Gatifloxacin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Meperidine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Sparfloxacin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Sertraline	The SSRI, Sertraline, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Sertraline is initiated, discontinued or dose changed.
Gatifloxacin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Meperidine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Sparfloxacin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Lithium	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Fluconazole	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Fluconazole, a strong CYP2C19 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Concomitant therapy should be used with caution.
Pergolide	Increased risk of serotonin syndrome. Pergolide, a strong CYP2D6 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Monitor for symptoms of serotonin syndrome and changes in Trimipramine therapeutic and adverse effects if Pergolide is initiated, discontinued or dose changed.
Amoxapine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Amiodarone	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Thiothixene	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Sitaxentan	The strong CYP2C19 inhibitor, Sitaxsentan, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Sitaxsentan is initiated, discontinued or dose changed.
Cocaine	The strong CYP2D6 inhibitor, Cocaine, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate.
Modafinil	The strong CYP2C19 inhibitor, Modafinil, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Modafinil is initiated, discontinued or dose changed.
Ritonavir	The strong CYP3A4/CYP2D6 inhibitor, Ritonavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Ritonavir is initiated, discontinued or dose changed.
Mefloquine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Sibutramine	Increased risk of serotonin syndrome. Concomitant therapy is contraindicated.
Propafenone	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Lapatinib	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Dextromethorphan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ticlopidine	The strong CYP2C19 inhibitor, ticlopidine, may decrease the metabolism and clearance of trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of trimipramine if ticlopidine is initiated, discontinued or dose changed.
Flupenthixol	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Mephentermine	Trimipramine may increase the vasopressor effect of the alpha1-agonist, Mephentermine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
Foscarnet	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Dasatinib	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Darunavir	The strong CYP3A4 inhibitor, Darunavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Darunavir is initiated, discontinued or dose changed.
Pentobarbital	The barbiturate, Pentobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Pentobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Galantamine	Possible antagonism of action
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Halofantrine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Orciprenaline	The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of orciprenaline.
Rizatriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Levofloxacin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, trimipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if rifampin is initiated, discontinued or dose changed.
Isradipine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Promethazine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Procainamide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Ergotamine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Fosamprenavir	The strong CYP3A4 inhibitor, Fosamprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Fosamprenavir is initiated, discontinued or dose changed.
Sotalol	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Fluvoxamine	The strong CYP2C19 inhibitor, fluvoxamine, may decrease the metabolism and clearance of trimipramine, a CYP2C19 substrate. Additive modulation of serotonin activity may also increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome and changes in therapeutic and adverse effects of trimipramine if fluvoxamine is initiated, discontinued or dose changed.
Mirtazapine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Probucol	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Loxapine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Thiopental	The barbiturate, Thiopental, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Thiopental is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Itraconazole	The strong CYP3A4 inhibitor, Itraconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Itraconazole is initiated, discontinued or dose changed.
Lopinavir	The strong CYP3A4/CYP2D6 inhibitor, Lopinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Lopinavir is initiated, discontinued or dose changed.
Sumatriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Guanabenz	Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Guanabenz. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Guanabenz should be withdrawn very gradually to reduce the risk of hypertensive crisis.
Nortriptyline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Chlorpromazine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Chlorpromazine, a strong CYP2D6 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Caution should be used during concomitant therapy.
Methadone	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Phenobarbital	The barbiturate, Phenobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Phenobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Erythromycin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Protriptyline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Doxepin	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Phenylpropanolamine	The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of phenylpropanolamine.
Rasagiline	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Methoxamine	Trimipramine may increase the vasopressor effect of the alpha1-agonist, Methoxamine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
Methylergonovine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Moclobemide	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Naratriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Flecainide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Clomipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Cimetidine	Cimetidine may increase the effect of tricyclic antidepressant, trimipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if cimetidine is initiated, discontinued or dose changed.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and trimipramine, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Cabergoline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Secobarbital	The barbiturate, Secobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Secobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Amobarbital	The barbiturate, Amobarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Amobarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Maprotiline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, trimipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used cautiously.
Nelfinavir	The strong CYP3A4 inhibitor, Nelfinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nelfinavir is initiated, discontinued or dose changed.
Dofetilide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
S-Adenosylmethionine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Cinacalcet	The strong CYP2D6 inhibitor, Cinacalcet, may decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Cinacalcet is initiated, discontinued or dose changed.
Ibutilide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Paroxetine	The SSRI, Paroxetine, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Paroxetine is initiated, discontinued or dose changed.
Cisapride	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Furazolidone	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Clarithromycin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Clarithromycin, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Concomitant therapy should be used with caution.
Escitalopram	The SSRI, Escitalopram, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Escitalopram is initiated, discontinued or dose changed.
Fenoterol	The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of fenoterol.
Dihydroergotamine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Phenelzine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Posaconazole	The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Posaconazole is initiated, discontinued or dose changed.
Nilotinib	May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Ergonovine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Saquinavir	The strong CYP3A4 inhibitor, Saquinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Saquinavir is initiated, discontinued or dose changed.
Haloperidol	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Terbinafine	Terbinafine may decrease the metabolism and clearance of Trimipramine. Consider alternate therapy or monitor for changes in Trimipramine efficacy and toxicity if Terbinafine is initiated, discontinued or dose changed. Alteration in Trimipramine dose may be required.
Norfloxacin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Tizanidine	Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Tizandine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Tizandine should be withdrawn very gradually to reduce the risk of hypertensive crisis.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Telithromycin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Telithromycin, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Concomitant therapy should be used with caution.
Guanethidine	The tricyclic antidepressant, trimipramine, decreases the effect of guanethidine.
Miconazole	The strong CYP3A4/2D6/2C19 inhibitor, Miconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/2D6/2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Miconazole is initiated, discontinued or dose changed.
Thioridazine	May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trimipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Dolasetron	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Droperidol	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Frovatriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ranolazine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of trimipramine by decreasing its metabolism. Additive QTc prolongation may also occur. Monitor for changes in the therapeutic and adverse effects of trimipramine if voriconazole is initiated, discontinued or dose changed.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Ergoloid mesylate	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Isoniazid	The strong CYP3A4/CYP2C19 inhibitor, Isoniazide, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Isoniazid is initiated, discontinued or dose changed.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tramadol	Tramadol may increase the risk of serotonin syndrome and seizures.
Risperidone	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
St. John's Wort	St. John's Wort may decrease serum concentrations of Trimipramine. Possible increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if St. John's Wort is initiated, discontinued or dose changed.
Quetiapine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Delavirdine	The strong CYP3A4/CYP2D6 inhibitor, Delavirdine, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2D6 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Delavirdine is initiated, discontinued or dose changed.
Midodrine	Trimipramine may increase the vasopressor effect of the alpha1-agonist, Midodrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
Dexmedetomidine	Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Dexmedetomidine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Dexmedetomidine should be withdrawn very gradually to reduce the risk of hypertensive crisis.
Isocarboxazid	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Nicardipine	The strong CYP3A4 inhibitor, Nicardipine, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nicardipine is initiated, discontinued or dose changed.
Buspirone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Methohexital	The barbiturate, Methohexital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Methohexital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Linezolid	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Octreotide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Nefazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Nefazodone, a strong CYP3A4 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Nefazodone is initiated, discontinued or dose changed.
Moxifloxacin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Epinephrine	Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Epinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
Guanfacine	Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Guanfacine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Guanfacine should be withdrawn very gradually to reduce the risk of hypertensive crisis.
Almotriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ketoconazole	The strong CYP3A4 inhibitor, Ketoconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Ketoconazole is initiated, discontinued or dose changed.
Butabarbital	The barbiturate, Butabarbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Butabarbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Abarelix	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Trimethobenzamide	Trimethobenzamide and Trimipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Amprenavir	The strong CYP3A4 inhibitor, Amprenavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Amprenavir is initiated, discontinued or dose changed.
Tranylcypromine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Duloxetine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Imipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Quinidine	Additive QTc-prolonging effects may occur, increasing the risk of serious cardiac arrhythmias. Quinidine, a CYP2D6/CYP3A4 inhibitor, may also inhibit the metabolism of Trimipramine, a CYP2D6/CYP3A4 substrate. Monitor for signs of cardiac arrhythmias and for changes in Trimipramine efficacy and toxicity if Quinidine is initiated, discontinued or dose changed.
Eletriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil	Possible antagonism of action
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Butalbital	The barbiturate, Butalbital, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Butalbital is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.
Clonidine	Trimipramine may reduce the antihypertensive effect of the alpha2-agonist, Clonidine. Trimipramine may also increase the rebound hypertensive effect of Clonidine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Clonidine if Trimipramine is initiated, discontinued or dose changed. Clonidine should be withdrawn very gradually to reduce the risk of hypertensive crisis.
Bromocriptine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trospium	Trospium and Trimipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Desipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Indapamide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine	Triprolidine and Trimipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Norepinephrine	Trimipramine may increase the vasopressor effect of the direct-acting alpha-/beta-agonist, Norepinephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
Disopyramide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Indinavir	The strong CYP3A4 inhibitor, Indinavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Indinavir is initiated, discontinued or dose changed.
Arsenic trioxide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Citalopram	The SSRI, Citalopram, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Citalopram is initiated, discontinued or dose changed.
Pimozide	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Gemfibrozil	The strong CYP2C19 inhibitor, Gemfibrozil, may decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Gemfibrozil is initiated, discontinued or dose changed.
Pentamidine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Omeprazole	The strong CYP2C19 inhibitor, Omeprazole, may decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Omeprazole is initiated, discontinued or dose changed.
Terbutaline	The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of terbutaline.
Selegiline	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Domperidone	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Amitriptyline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Tetrabenazine	May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
Pseudoephedrine	The tricyclic antidepressant, trimipramine, increases the sympathomimetic effect of pseudoephedrine.
Procarbazine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
Atazanavir	The strong CYP3A4 inhibitor, Atazanavir, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Atazanavir is initiated, discontinued or dose changed.
Pramlintide	The anticholinergic effects of Trimipramine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, trimipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of trimipramine if rifabutin is initiated, discontinued or dose changed.
Perflutren	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Sunitinib	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Mesoridazine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Phenylephrine	Trimipramine may increase the vasopressor effect of the alpha1-agonist, Phenylephrine. Avoid combination if possible. Monitor sympathetic response to therapy if used concomitantly.
Imatinib	The strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Imatinib is initiated, discontinued or dose changed.