From Birth Control to Blood Thinners: 9 Melatonin Interactions to Be Aware of

Melatonin is an over-the-counter (OTC) supplement widely used as a sleep aid. Taking it may help you fall asleep faster or recover from jet lag. Melatonin comes in various formulations, such as capsules, gummies, and topical patches. But just because it’s available without a prescription doesn’t mean it’s safe to take with your other medications.

Below, we will review nine melatonin interactions you should know about. Remember that this is not a complete list. It’s always best to check with your healthcare team before starting an OTC supplement.

1. Certain antidepressants, such as Prozac

Some antidepressants can raise melatonin levels in your body. So taking extra melatonin with them can make you feel more drowsy or lead to a headache or upset stomach. Nortriptyline (Pamelor) and fluvoxamine (Luvox) are the antidepressants most likely to have this effect.

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Some selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and citalopram (Celexa), may also raise melatonin levels. The interaction is more likely if these SSRIs are combined with proton pump inhibitors such as omeprazole (Prilosec).

Melatonin is actually formed from serotonin. So it’s possible that the reason for this interaction is the higher levels of serotonin these antidepressants cause.

You may need a lower melatonin dose if you’re taking one of these medications. Or you may need to avoid it altogether. Your mental health care team can help guide you on the best course of action.

Good to know: Melatonin supplements aren’t well regulated. And some have been found to contain serotonin in addition to melatonin. If you take a melatonin supplement that has hidden serotonin with an antidepressant, a serious condition called serotonin syndrome can happen. So be sure to only purchase melatonin from reputable sources. And if you develop symptoms such as sweating, confusion, and a high fever while taking a melatonin supplement with your antidepressant medication, seek medical care right away. 

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2. Nifedipine

Nifedipine (Procardia, Procardia XL) belongs to a class of medications called calcium channel blockers. It’s a common medication for high blood pressure. Melatonin can make nifedipine less effective if they’re taken together. This may cause a rise in your blood pressure.

If you take nifedipine, talk to your prescriber before taking melatonin. They may give you tips for improving your sleep hygiene, or suggest you try a different medication to help you sleep. Or they may want you to check your blood pressure more often while taking melatonin. Be sure to report any high blood pressure readings to your medical care team. If your blood pressure is too high, it can raise your risk of heart disease and stroke.

3. Warfarin and other blood thinners

Warfarin (Coumadin) is a medication used to prevent unwanted blood clots. Melatonin can enhance warfarin’s blood thinning effects, putting you at a greater risk of bleeding. Fortunately, there have been no reports of life-threatening bleeding with this interaction. But it’s still good to be aware of.

You’ll likely have regular blood tests while you’re taking warfarin to make sure it’s working properly. But you may need more frequent testing when you start taking melatonin. So be sure to let your prescriber know if you plan to start taking it. And they’ll need to know if you stop taking it, too. They’ll use your blood test results to decide if you need a change in your warfarin dose while you’re taking melatonin, or after you stop it.

While melatonin doesn’t directly interact with other blood thinner medications, it can still raise your risk of bleeding. So keep an eye out for any new bruising or bleeding if you’re taking melatonin with other blood thinners.

Let your prescriber know if any signs of bleeding appear while you’re taking melatonin with warfarin or other blood thinners. And seek medication attention right away if you notice signs of serious bleeding, such as blood in your urine or stool.

Good to know: This interaction doesn’t seem to apply to nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin, Advil) and naproxen (Aleve). Although these medications can raise your risk of bleeding, they can also lower the amount of melatonin your body makes. So there doesn’t seem to be an issue with taking them together once in a while, if needed. But if you’re taking NSAIDs long-term, talk to your prescriber before taking melatonin.  

4. Other medications and substances that make you sleepy, such as Benadryl and alcohol

Melatonin may enhance the sedative effects of other medications if you take them together. This could cause extra drowsiness or impair your ability to think clearly. It can also raise the risk of next-day drowsiness (hangover effect). This could impact your ability to drive or perform other tasks that require your full attention.

Medications that could cause these effects when combined with melatonin include:

• Z-drugs such as zolpidem (Ambien) and zaleplon (Sonata) 

• Benzodiazepines such as alprazolam (Xanax) and diazepam (Valium)

• Some antidepressants, such as trazodone and amitriptyline (Elavil)

• First-generation antihistamines, such as diphenhydramine (Benadryl)

• Opioid pain medications

• Muscle relaxants, such as cyclobenzaprine (Flexeril) and carisoprodol (Soma)

• Alcohol

• Cannabis

• Sleep supplements such as valerian, tryptophan, and kava

5. Caffeine

Caffeine can raise melatonin levels in your body if they’re taken together. Caffeine blocks the liver enzyme (protein) that breaks down melatonin. Some people’s melatonin levels more than doubled in a small study looking at this interaction.

This interaction is significant, but it’s unlikely to be an issue. Why? Because it’s not common to consume caffeine right before you’re trying to sleep — which is when most people take melatonin.

That being said, keep in mind that soda, energy drinks, and tea can contain caffeine you may not be aware of. It’s best to cut off caffeine intake about 6 hours before bedtime to prevent it from affecting your sleep and your melatonin levels.      

6. Oral contraceptive pills

Melatonin won’t interfere with your birth control. But it’s possible that oral contraceptive pills may cause your body to make more melatonin than it normally would. Adding a melatonin supplement may further raise melatonin levels, which could lead to unwanted side effects.

There’s not a lot of evidence about how much of an issue this interaction may be. But if you’re taking oral birth control pills, it’s a good idea to start with a low dose of melatonin to avoid unwanted side effects.

7. Diabetes medications

Melatonin may lower your blood sugar levels. If you’re living with diabetes, you may already take a medication that lowers your blood glucose (sugar). Combining melatonin with these medications may cause your blood glucose to drop too low (hypoglycemia).

Evidence of this interaction is conflicting. And since most people take melatonin at bedtime, it’s not likely to interfere with diabetes medications you take with meals during the day. Still, if you’re taking medication for diabetes, talk with your healthcare team before starting melatonin. They may suggest monitoring your blood glucose more often or starting on a low dose of melatonin to see how it affects you. Having glucose tablets or gel handy is always a good idea in case you have an episode of hypoglycemia.

8. Blood pressure medications

Melatonin, especially slow-release formulations, can lower your blood pressure. Older adults may be more susceptible to this effect. Taking melatonin with other medications that lower blood pressure may cause your blood pressure to drop too low (hypotension). Examples include:

• Beta blockers

• Angiotensin-converting enzyme (ACE) inhibitors

• Calcium-channel blockers

• Diuretics

If you’re taking medication to lower your blood pressure, talk with your prescriber before starting melatonin. They may want you to monitor your blood pressure more often. If your blood pressure drops, or you feel dizzy, weak, or faint, let your medical care team know. You may need a lower dose of melatonin or to stop taking it altogether.

9. Immunosuppressants

Immunosuppressant medications decrease the activity of your immune system. They’re often prescribed for autoimmune conditions or after an organ transplant. Examples include:

• Corticosteroids

• Chemotherapy

• Organ transplant medications, such as cyclosporine (Sandimmune, Neoral, Gengraf)

• Some biologics, such as adalimumab (Humira) and ustekinumab (Stelara)

Melatonin has the opposite effect — it can activate your immune system. This could make your immunosuppressant medication less effective.

If you’re taking an immunosuppressant, a different sleep medication may be a better option for you. Talk to your prescriber about other options that won’t affect your medication.

Can you take melatonin with antibiotics?

Some antibiotics, such as fluoroquinolones and erythromycin, may increase melatonin levels if they’re taken together. But since antibiotics are usually only taken for a short period of time, this interaction isn’t likely to cause a serious issue. But it may be a good idea to lower your melatonin dosage until you’ve finished your course of antibiotics.

Ask your prescriber or pharmacist if it’s OK to take melatonin with your antibiotic. They’ll let you know if there’s an interaction you should know about.  

Can you take melatonin with acetaminophen (Tylenol)?

There doesn’t seem to be any issue with taking melatonin and acetaminophen (Tylenol) together. That being said, it’s best to check with your pharmacist or medical care team to make sure both medications are OK for you based on your other medications and health conditions.

When should you seek medical care for a melatonin interaction?

The best time to talk with your healthcare team about interactions is before you start taking melatonin. They can review your medication list for any possible interactions, and let you know if melatonin is a safe option for you.

If you notice a change in how you’re feeling or new side effects or symptoms while taking melatonin, let your healthcare team know. They can check to see if an interaction could be the cause. But if you feel your symptoms are severe, don’t hesitate to seek emergency care or call 911.

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Written by:

Emilie White, PharmD

Emilie White is a clinical pharmacist with over a decade of hospital pharmacy experience. Her professional areas of interest include critical care as well as infectious and autoimmune diseases.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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