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Belsomra Drug Interactions—Understanding the Risks

Belsomra Drug Interactions—Understanding the Risks

In this day and age, people often have trouble falling asleep right away. Whether it’s due to anxiety over the following work day or bedtime procrastination, not getting enough sleep can affect your daily performance—which can, again, make it harder to fall asleep. After all, healthy sleep habits take time and effort to create and maintain. And the longer you wait, the harder it gets to do something about it on your own.

If you’re one of many who have trouble falling asleep, you may benefit from a sleep medication such as Belsomra. This drug can help with falling asleep and maintaining it throughout the night—as long as you use it responsibly. A significant part of that is knowing what medicines cannot be taken with Belsomra.

This article will cover the most notable Belsomra drug interactions. Since the list isn’t exhaustive, you should always check with your doctor before starting any new medication or modifying your existing treatment.

Belsomra—General Information

Belsomra belongs to a drug class called dual orexin receptor antagonists (DORAs). It prevents orexins, neurotransmitters causing wakefulness, from binding to their respective receptors. It can help you achieve a full night’s sleep, from the onset to waking up in the morning.

Belsomra should be taken 30 minutes before bedtime, but only when you can sleep for at least seven hours, as the drug can make you feel groggy the next day.

Learn more about Belsomra in the table below:



Main substance


Generic versions


FDA approved

Yes, in 2014

Controlled substance

Yes, Schedule IV

Available doses

5 mg, 10 mg, 15 mg, 20 mg

Starting dose

10 mg

Daily limit

20 mg

Usual cost

Around $400 to $500

Belsomra Drug Interactions To Consider

Source: Kinga Howard

Currently, Belsomra is known to interact with 465 drugs. The ones manufacturers caution against most include other central nervous system (CNS) depressants and CYP3A inhibitors and inducers.

The lists of drug interactions in this article are not comprehensive, which is why you should always be transparent about all medications or supplements you’re taking. That way, the doctor can decide whether you can take Belsomra safely and which dosage is right for you.

Belsomra and Other CNS Depressants

Belsomra is a CNS depressant and slows down brain activity. Combining it with other CNS depressants can have additive effects, leading to a state of CNS depression, which is characterized by:

  • Slowed breathing
  • Slurred speech
  • Impaired judgment
  • Confusion
  • Lethargy
  • Lack of coordination

Some of the most popular CNS depressants that can interact with Belsomra include:

  • Other DORAs—Dayvigo (lemborexant), Quviviq (daridorexant)
  • Sedative hypnotics—Ambien (zolpidem), Lunesta (eszopiclone), Sonata (zaleplon)
  • Benzodiazepines—Xanax (alprazolam), Valium (diazepam), Ativan (lorazepam)
  • Barbiturates—Luminal (phenobarbital), butalbital, amobarbital
  • Opioids—Ultram (tramadol), alfentanil, codeine
  • Anti-seizure medications—Klonopin (clonazepam), Neurontin (gabapentin), Dilantin (phenytoin)

If you happen to be taking one of these medications during Belsomra treatment, the doctor will consider a lower dose of either drug.

Belsomra and CYP3A Inhibitors and Inducers

Source: Ketut Subiyanto

Belsomra is metabolized primarily by the CYP3A enzyme. It can thus interact with medications that affect said enzyme.

CYP3A inhibitors reduce the activity of the enzyme. They can increase the levels of Belsomra in your blood, enhancing its effects and adverse reactions. Official prescribing information discourages the use of Belsomra with strong CYP3A inhibitors, including:

  • Antifungals such as ketoconazole, itraconazole, and posaconazole
  • HIV infection medications such as nefazodone, ritonavir, saquinavir, nelfinavir, and indinavir
  • Antiviral medications such as boceprevir and telaprevir
  • Antibiotics such as clarithromycin and telithromycin
  • Vasopressin antagonists such as conivaptan

When it comes to moderate CYP3A inhibitors, the recommended daily dose of Belsomra is 5 mg, and it can be increased to 10 mg for efficacy’s sake. Moderate CYP3A inhibitors include:

  • HIV infection medications such as amprenavir, atazanavir, and fosamprenavir
  • Antibiotics such as ciprofloxacin and erythromycin
  • Antifungals such as fluconazole
  • Antiemetics such as prepitant
  • Chemotherapy medication such as imatinib
  • Heart and blood pressure medication such as diltiazem and verapamil
  • Grapefruit juice

The effects of Belsomra may be reduced when the medication is taken with strong CYP3A inducers, including:

  • Antibiotics such as rifampin
  • Anti-seizure medications such as carbamazepine and phenytoin

Other Belsomra Drug Interactions

Belsomra can interact with many other medications, including the ones listed in the table below:

Type of Drug


What Can Happen

Blood pressure medication 

  • Digoxin

Belsomra can increase the levels of digoxin in the blood and the risk of side effects (nausea, vomiting, visual disturbances). The doctor should monitor digoxin concentrations during the concomitant treatment

Cholesterol-lowering medication

The levels of these medications in blood can be increased when combined with Belsomra, resulting in side effects such as liver damage. Dosage adjustment and close monitoring are recommended


  • Trazodone

  • Cymbalta (duloxetine)

  • Amitriptyline 

Using Belsomra and Cymbalta or another antidepressant may increase Belsomra side effects, such as dizziness and difficulty concentrating. Some individuals, especially the elderly, may experience impairment in judgment and motor coordination

Muscle relaxants

  • Lioresal (baclofen)

  • Amrix (cyclobenzaprine)

  • Zanaflex (tizanidine)

A muscle relaxer like baclofen and Belsomra combined can increase side effects like psychomotor impairment, particularly in the elderly


  • Seroquel (quetiapine)

  • Risperdal (Risperidone)

  • Olanzapine

Combining Belsomra and specific antipsychotics can enhance the side effects of Belsomra, especially in the elderly


Simultaneously using an antihistamine, such as Benadryl, with Belsomra may increase the side effects, particularly in the elderly

Other Substances Belsomra Can Interact With

Belsomra can also interact with specific supplements, foods, and drinks:

  • Alcohol—Like Belsomra, alcohol is a CNS depressant. Combining these two substances can produce additive effects and intensify the psychomotor impairment. If you are attending a social event or a party of some kind, and you’re planning on drinking alcohol, avoid taking Belsomra that evening
  • St. John’s Wort—This herb can decrease the level of suvorexant in blood, reducing the medication’s effectiveness
  • Melatonin—These two sleep aids have similar effects. Taking Belsomra and melatonin together may enhance side effects like drowsiness, especially in older individuals
  • Cannabis—Similarly to melatonin, mixing Belsomra with cannabis or cannabis products like CBD can increase the side effects of Belsomra
  • Caffeine—Caffeine is a stimulant that interferes with sleep. It can be found in coffee, tea, energy drinks, and chocolate. If you like drinking coffee or snacking on some chocolate in the afternoon, know that it can decrease the effects of Belsomra
  • Grapefruit—Grapefruit and grapefruit juice are moderate CYP3A inhibitors. They can increase the levels of Belsomra in blood, raising the risk of side effects

Belsomra—A Brief Guide to Safe Use

Before the doctor prescribes Belsomra, they’ll ask you about your current condition, medical history, and medications or supplements you’re on. If you have or have had any of these conditions, the doctor will likely suggest a lower dose or an alternative:

  1. Narcolepsy or cataplexy
  2. Severe liver problems
  3. Breathing problems
  4. Depression and substance abuse problems
  5. Suvorexant allergy

The doctor will monitor you for a few days to confirm that you’re taking the lowest effective dose. You must take Belsomra precisely as prescribed—30 minutes before bed and with at least seven hours of sleep ahead.

If insomnia persists or becomes more severe after seven to ten days of treatment, you may be suffering from another condition that requires a different approach.

Source: William Fortunato

Prescription medications, such as Belsomra, can be an excellent temporary solution to sleeplessness. Still, sleep issues are complex, and to eliminate them, you should also consider non-pharmaceutical solutions. For instance, cognitive behavioral therapy for insomnia (CBT-I) can help you reframe the thoughts, feelings, and behaviors that cause the condition in the first place. Combined with fast-acting sleep medications, it is an effective treatment for both occasional and chronic insomnia.

The holistic approach to sleeplessness requires specialists who can design personalized treatment plans and not resort to generic drugs. Unfortunately, even though sleep problems are widespread today, sleep medicine specialists are scarce. To help you get the expert assistance you need quickly, Kick has developed a convenient online sleep program.

Kick—Sleep Science at Your Fingertips

Designed by a Stanford sleep doctor, Kick offers you an effective solution tailored to your particular needs and medical history. Kick’s program allows you to get in touch with a sleep medicine specialist remotely within 24 hours and get two different medications delivered to your home or local pharmacy in no time.

Our selection of medications is the largest in the industry, and it consists of:

  1. Trazodone
  2. Atarax and Vistaril (hydroxyzine)
  3. Neurontin (gabapentin)
  4. Flexeril and Amrix (cyclobenzaprine)
  5. Rozerem (ramelteon)

With fast-acting formulations and ongoing support from our sleep doctor, you can achieve your best night’s sleep and keep it. Besides medications, the doctor will provide CBT-I coaching to tackle sleeplessness on all fronts.

Source: Thirdman

Try Kick and Wake Up Energized

To start your Kick sleep improvement journey, follow these steps:

  1. Navigate to the signup page and take a 15-minute online sleep visit
  2. Fill out the form that gathers info about your sleep issues and medical history
  3. Provide the delivery address and payment details

One of our doctors will get back to you via text within a day. In case they determine Kick is not a suitable solution for you, they’ll direct you to your primary care doctor. More importantly, you won’t have to pay for the consultation according to our “Doctor Guarantee” policy.

Kick’s glowing Trustpilot reviews are the best indicator of the effectiveness and commitment to providing exceptional customer care. If you want to make your nights more peaceful and refreshing, sign up for Kick and get a comprehensive custom treatment plan.

Featured image source: Polina Kovaleva