Written by Emilie White, PharmD | Reviewed by Alyssa Billingsley, PharmD
Updated on February 16, 2024
Key takeaways:
Melatonin is an over-the-counter sleep aid that interacts with several medications. Caffeine, certain antidepressants, and oral birth control pills can raise melatonin levels in the body. This increases your risk of melatonin side effects.
Melatonin may make nifedipine and immunosuppressants less effective. It can also raise your risk of low blood glucose, low blood pressure, and bleeding if you take it with other medications that have these effects.
It’s best to avoid taking melatonin with alcohol, cannabis, and other medications that cause drowsiness. This includes medications like Benadryl, diazepam, and opioids.
Table of contents
Antidepressants
Nifedipine
Blood thinners
Other sedatives
Caffeine
Birth control
Diabetes meds
Blood pressure meds
Immunosuppressants
When to seek care
Bottom line
References
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.
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.
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.
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.
Warfarin and other blood thinnersWarfarin (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.AdvertisementAdvertisementYou’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.
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
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.
Oral contraceptive pillsMelatonin 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.
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.
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.
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.
The bottom line
Melatonin is an OTC supplement that may help you get a good night’s rest. But it can interact with several other medications. Caffeine, some antidepressants, and oral birth control pills can raise melatonin levels in the body.
Melatonin can increase your risk of bleeding if you take it with warfarin or other blood thinners. It can also make nifedipine and immunosuppressant medications less effective. Melatonin may make low blood pressure and low blood glucose more likely if you’re taking other medications that have these effects. It can also raise your risk of sedation and next-day drowsiness if you take it with other medications that make you drowsy.
Before starting melatonin, show your medical care team or pharmacist your updated medication list. This helps them identify any possible drug interactions before they happen.
References
Reference 2
Carvalho, L., et al. (2009). Effect of antidepressants on melatonin metabolite in depressed patients. Journal of Psychopharmacology.
View All References (8)
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