Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: disopyramide, certain drugs for high blood pressure (such as clonidine, guanadrel, guanethidine), digoxin, thyroid supplements, valproic acid.

Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.

The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including SSRIs such as fluoxetine/paroxetine, SNRIs such as duloxetine/venlafaxine), among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.

Other medications can affect the removal of desipramine from your body, which may affect how desipramine works. Examples include barbiturates (such as phenobarbital), cimetidine, haloperidol, certain drugs for heart rhythm (such as flecainide, propafenone), halofantrine, HIV protease inhibitors (such as fosamprenavir), phenothiazines (such as thioridazine), pimozide, certain anti-seizure drugs (such as phenytoin), antidepressants (such as trazodone), among others.

Cigarette smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking.

Many drugs besides desipramine may affect the heart rhythm (QT prolongation in the EKG), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, sparfloxacin, macrolide antibiotics (such as erythromycin), among others. Before using desipramine, report all medications you are currently using to your doctor or pharmacist.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), and opioid pain relievers (such as codeine, hydrocodone).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Desipramine is very similar to imipramine. Do not take medications containing imipramine while using desipramine.