Learn about major and moderate Imipramine drug interactions, supplements to avoid, food interactions, and what to tell your doctor before starting.
Imipramine (brand name Tofranil) is a tricyclic antidepressant that interacts with a significant number of other medications, supplements, and even certain foods. Some of these interactions can be dangerous — even life-threatening.
Before starting Imipramine, your doctor needs to know everything you're taking. This guide covers the most important interactions to be aware of.
Drug interactions happen in a few ways:
These combinations should be avoided or require very careful medical supervision.
This is the most dangerous interaction. Taking Imipramine with an MAO inhibitor — including Phenelzine (Nardil), Tranylcypromine (Parnate), Isocarboxazid (Marplan), and Selegiline (Emsam) — can cause hypertensive crisis (dangerously high blood pressure) and serotonin syndrome.
You must wait at least 14 days after stopping an MAO inhibitor before starting Imipramine, and vice versa. This also applies to Linezolid (an antibiotic) and intravenous Methylene Blue, which have MAO-inhibiting properties.
SSRIs like Fluoxetine (Prozac) and Paroxetine (Paxil) are strong inhibitors of the CYP2D6 enzyme. Taking them with Imipramine can dramatically increase Imipramine blood levels, raising the risk of side effects including cardiac arrhythmias and seizures. If a switch between these medications is needed, a washout period may be required.
This heartburn medication inhibits several liver enzymes and can significantly increase Imipramine levels. If you need an acid reducer, your doctor may recommend alternatives like Famotidine (Pepcid) instead.
Imipramine can block the blood pressure-lowering effects of Clonidine, potentially causing dangerous blood pressure spikes. This combination should be avoided.
Imipramine already has strong anticholinergic effects. Adding other anticholinergic medications — such as Oxybutynin (Ditropan), Diphenhydramine (Benadryl), or Benztropine (Cogentin) — can lead to severe dry mouth, urinary retention, constipation, confusion, and even delirium, especially in elderly patients.
Combining Imipramine with other drugs that depress the central nervous system increases the risk of extreme drowsiness, impaired coordination, and respiratory depression. These include:
These combinations may require dose adjustments or extra monitoring.
These anticonvulsants speed up Imipramine metabolism, lowering its levels and potentially reducing its effectiveness. Your doctor may need to increase your Imipramine dose.
Thyroid hormones like Levothyroxine can increase the effects of Imipramine, including both therapeutic effects and side effects. Close monitoring is important if you're on both.
Drugs like Epinephrine and Pseudoephedrine (found in many cold medications) can have potentiated cardiovascular effects when taken with Imipramine, including increased heart rate and blood pressure.
Imipramine can block the antihypertensive effect of Guanethidine, making it harder to control blood pressure.
This ADHD medication can increase Imipramine levels in the blood. If both are prescribed together, your doctor should monitor for increased side effects.
This herbal supplement has serotonergic properties and should not be taken with Imipramine. The combination increases the risk of serotonin syndrome — a potentially life-threatening condition with symptoms like agitation, rapid heart rate, high fever, and muscle rigidity.
As mentioned above, this common OTC antihistamine has anticholinergic properties that add to Imipramine's. Avoid using them together regularly.
Found in many cold and sinus medications (Sudafed, DayQuil), these decongestants can cause blood pressure spikes when combined with Imipramine. Check labels carefully.
Generally considered safe with Imipramine, but the combination may increase drowsiness. Use with caution.
Alcohol is a CNS depressant and should be avoided or minimized while taking Imipramine. The combination increases drowsiness, impairs judgment, and can worsen depression.
Grapefruit juice can inhibit liver enzymes that process Imipramine, potentially increasing drug levels in your blood. While the interaction is generally mild, it's worth mentioning to your doctor if you drink grapefruit juice regularly.
Before starting Imipramine, make sure your doctor and pharmacist know about:
This information helps your doctor avoid dangerous combinations and adjust doses if needed.
For a complete overview of Imipramine, read our guide on what Imipramine is and how it's used. If you're looking for Imipramine at a pharmacy near you, Medfinder can help you find it in stock.
Imipramine is an effective medication, but its interaction profile is broader than newer antidepressants. The most critical interactions to avoid are MAO inhibitors, certain SSRIs, and heavy alcohol use. Always keep your healthcare providers informed about everything you're taking — including supplements and over-the-counter products — so they can keep you safe while you get the treatment you need.
You focus on staying healthy. We'll handle the rest.
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