See also Precautions section.

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 are: certain antihypertensive medications (such as clonidine, guanabenz, methyldopa), other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen/naproxen, "blood thinners" such as dabigatran/warfarin), disulfiram, lithium, thyroid supplements.

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.

Other medications can affect the removal of perphenazine/amitriptyline from your body, which may affect how this medication works. Examples include cimetidine, azole antifungals (such as ketoconazole, itraconazole), drugs to treat irregular heartbeat (such as amiodarone, flecainide, propafenone, quinidine), macrolide antibiotics (such as erythromycin), rifamycins (such as rifabutin), anti-HIV drugs (such as fosamprenavir), ritonavir, SSRI antidepressants (such as fluoxetine, paroxetine), St. John's wort, among others.

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

Many drugs besides perphenazine/amitriptyline may affect the heart rhythm (QT prolongation). Examples include amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others.

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.

Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has told you to take low-dose aspirin to prevent heart attack or stroke (usually 81-162 milligrams a day), you should keep taking the aspirin unless your doctor tells you not to. Ask your doctor or pharmacist for more details.

Amitriptyline is very similar to nortriptyline. Do not use medications containing nortriptyline while using amitriptyline.