Subsys (fentanyl) is a strong opioid medication that's used to relieve breakthrough pain in adults with cancer who already take around-the-clock opioid pain medications. Subsys (fentanyl) is sprayed under the tongue. Side effects include nausea, constipation, and sleepiness. It also has a risk for slowed breathing and misuse.
Please note: Subsys (fentanyl) has been discontinued and is no longer available in the United States. Talk to your provider about alternative options to treat your pain.
Breakthrough cancer pain in adults 18 years and older
Subsys (fentanyl) is an opioid. It attaches to certain mu-opioid receptors in your brain to lower how much pain you feel.
Subsys (fentanyl) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Risk factors: Personal or family history of alcohol or substance use disorder | Personal or family history of mental health problems
Subsys (fentanyl) is a controlled substance that has a risk for addiction and misuse. Take the medication exactly as prescribed. Don't change the dose or how often you take it without talking to your provider first.
Misusing Subsys (fentanyl) might cause it to work less well. It can also raise the risk for serious and possibly life-threatening side effects, such as dangerously slow breathing, inability to stay awake, and opioid overdose. Your healthcare provider will prescribe the lowest amount of Subsys (fentanyl) that's necessary to manage your pain for the shortest period of time possible.
Because of the risk for misuse, addiction, and overdose, Subsys (fentanyl) is included in the Risk Evaluation and Mitigation Strategy (REMS) program called the Transmucosal Immediate Release Fentanyl (TIRF) REMS program. Healthcare providers and pharmacies must register with the program, receive training on proper medication use, and discuss safe medication use with you.
Risk factors: Taking medications that can cause slow breathing | Drinking alcohol | Older age | Being frail | Medical conditions that cause breathing problems (e.g., COPD, asthma, head injury) | Taking too much Subsys (fentanyl)
Opioids like Subsys (fentanyl) can cause dangerously slow breathing, which can be life-threatening. This can happen to anyone at recommended doses. But the risk is greatest when you first start treatment or if your dose goes up.
Don't take an opioid with alcohol or other medications that slow your body down (e.g., benzodiazepines, other opioids, muscle relaxants). Doing so raises your risk of extremely slowed breathing.
Your provider might prescribe naloxone (Narcan), a medication that can reverse slowed breathing from opioids. Carry it with you at all times in case you have breathing problems from the opioid medication. If you or your loved one notices that you have trouble breathing or bluish-colored lips, fingers, or toes, use naloxone if you have it and call 911 to get medical help right away.
Risk factors: History of opioid use disorder | Previous opioid overdose | Taking high doses of Subsys (fentanyl) | Taking more opioids than prescribed | Alcohol use
Take opioid medications exactly as prescribed. Taking too much or taking it more often than prescribed can lead to an overdose. In addition, it can be especially dangerous if a child accidentally ingests opioid medications, such as Subsys (fentanyl). Store your medication out of reach from children, pets, or visitors to prevent accidental exposure or overdose.
Symptoms of an opioid overdose include not responding to sound or touch, extremely slowed breathing, extreme sleepiness, slow heartbeat, and cold or clammy skin. Be sure you and your loved ones know how to recognize an overdose. Your provider will probably prescribe naloxone (Narcan), a medication that can treat an opioid overdose. Carry naloxone with you at all times in case an overdose happens, and call 911 right away if this happens.
Risk factors: Taking high doses of Subsys (fentanyl) | Age 65 years or older | Drinking alcohol | Taking other medications that can cause sleepiness
Opioids can cause extreme sleepiness and lower your ability to think, react, and focus. Don't drink alcohol or take other medications that can cause sleepiness or "brain fog" (e.g., benzodiazepines, muscle relaxants, sleep medications) with Subsys (fentanyl). Doing so can worsen these side effects. Make sure you know how your opioid medication affects you before driving a car or doing activities that require your concentration. Talk to your healthcare provider right away if you feel too sleepy from taking Subsys (fentanyl).
Long-term use of opioids during pregnancy can cause your unborn baby to become dependent on the medication. This is because the opioid (fentanyl) can pass through the placenta to your unborn baby. Once your baby is born, they can experience withdrawal symptoms, such as high-pitched crying, poor feeding and sucking behavior, trembling, abnormal sleep patterns, and seizures. This condition is called neonatal opioid withdrawal syndrome and can be life-threatening if not recognized and treated in time. Let your healthcare provider know if you've used Subsys (fentanyl) or other opioids during pregnancy or if you notice these symptoms in your baby.
Tell your providers about all of the medications you're taking or planning to take with opioids like Subsys (fentanyl). Taking certain medications with opioids or changing your medication routine can raise your risk for dangerous side effects. Benzodiazepines, sedatives, and alcohol can worsen opioid side effects like slow breathing or severe sleepiness and can be life-threatening. In addition, taking opioids like Subsys (fentanyl) with certain antidepressants can also raise your risk of serotonin syndrome, a rare but serious side effect that can lead to fast heart rate, sweating, and muscle problems.
Risk factors: Long-term use of Subsys (fentanyl)
Opioids like Subsys (fentanyl) can cause physical dependence when they're taken for a long time. This means that your body relies on the medication to function. You might experience withdrawal if you stop taking the medication suddenly or lower your dose too fast.
Withdrawal symptoms include anxiety, restlessness, irritability, sweating, and chills. Don't lower your dose or stop taking the medication suddenly without talking to your healthcare provider first. Your provider will slowly lower your dose to prevent withdrawal symptoms. Talk to your provider about alternative pain medications if you have concerns about the risk for dependence and withdrawal from opioid use.
Subsys (fentanyl) and other opioids can cause extremely low blood pressure. Your blood pressure might drop suddenly when you stand from a sitting or lying down position. This can lead to dizziness and fainting. To avoid falling, get up slowly if you've been sitting or lying down. Talk to your healthcare provider if dizziness or lightheadedness doesn't go away.
Risk factors: Taking Subsys (fentanyl) for longer than 1 month
Some people taking opioids like Subsys (fentanyl) had low adrenal hormone levels. This might be more likely to happen after taking opioids for longer than 1 month. Symptoms include tiredness, dizziness, weakness, not feeling hungry, nausea, and vomiting. Let your provider know if you have these symptoms. If your adrenal hormone levels are too low, you might need to stop Subsys (fentanyl) and be treated with corticosteroids.
Risk factors: History of seizure conditions
If you've had a seizure in the past, opioids can raise the risk of having seizures more often. Subsys (fentanyl) can also raise your risk of seizures in certain situations. Get medical help immediately if you have a seizure while you're taking this medication.
Source:Â DailyMed
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
Black, tarry stools
blurred vision
confusion
convulsions
decreased urine
difficult or labored breathing
dizziness
fainting
fever or chills
increased thirst
irregular heartbeat
lightheadedness
loss of appetite
lower back or side pain
mood changes
muscle pain or cramps
nausea or vomiting
nervousness
numbness or tingling in the hands, feet, or lips
painful or difficult urination
pale skin
pounding in the ears
rapid breathing
sunken eyes
swelling of the hands, ankles, feet, or lower legs
tightness in the chest
troubled breathing with exertion
ulcers, sores, or white spots in the mouth
unusual bleeding or bruising
unusual tiredness or weakness
wrinkled skin
Less common
Abdominal or stomach pain
change in walking and balance
clumsiness or unsteadiness
decreased awareness or responsiveness
decreased frequency of urination
headache
muscle twitching or jerking
pounding in the ears
rhythmic movement of the muscles
seeing, hearing, or feeling things that are not there
seizures
severe constipation
severe sleepiness
shakiness in the legs, arms, hands, or feet
slow or fast heartbeat
thinking abnormalities
trembling or shaking of the hands or feet
Get emergency help immediately if any of the following symptoms of overdose occur:
Symptoms of overdose
Extremely shallow or slow breathing
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
Back pain
difficulty having a bowel movement (stool)
difficulty with moving
discouragement
feeling sad or empty
irritability
lack or loss of strength
loss of interest or pleasure
muscle stiffness
pain in the joints
sleepiness or unusual drowsiness
tiredness
trouble concentrating
trouble sleeping
Less common
Changes in vision
excessive muscle tone
feeling of constant movement of self or surroundings
feeling of warmth or heat
flushing or redness of the skin, especially on the face and neck
irritation, pain, or sores at the site of application
itching skin
muscle tension or tightness
rash
sensation of spinning
sweating
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Can work within 5 minutes to relieve breakthrough cancer pain
Comes with a portable pouch and child-resistant lock and latches for safe storage and handling
Only for cancer pain (not for other types of short-term pain)
Can only be used if you already take opioids around-the-clock (opioid-tolerant)
Can have a lot of side effects, such as nausea, vomiting, constipation, and sleepiness
Opioid medications can make you sleepy and affect your ability to think, react, and focus. Don't drive or do activities that you need to be alert for until you know how this medication affects you.
Opioid medications like Subsys (fentanyl) can cause constipation. Ask your provider for recommendations if you become constipated while you're taking this medication. Some over-the-counter medications for constipation include senna (Sennokot) and polyethylene glycol (Miralax). There are also prescription medications for constipation if you need even more relief.
Tell your providers and pharmacists about all the medications you're taking or planning to take with opioids like Subsys (fentanyl). Many medications can interact with Subsys (fentanyl) and cause the pain medication to work less well or raise your risk for harm, such as slow breathing, severe sleepiness, or even overdose.
Your provider or pharmacist will talk to you about naloxone (Narcan), a medication that can be used in emergency situations for accidental opioid overdose. Tell your family and close friends where you'll keep it in case an overdose happens. Signs of an overdose include slowed breathing, sleepiness, muscle weakness, small pupils, cold or clammy skin, or unresponsiveness. If you use naloxone (Narcan) for an overdose, you should still call 911 because its effects are temporary.
Your provider will work with you to prescribe the right dose of Subsys (fentanyl) for your individual needs. It's recommended to use the lowest dose possible for the shortest duration of time to manage your pain.
The typical starting dose is one spray (100 mcg) under your tongue (sublingually) to treat one episode of breakthrough pain. Ask your provider what you should do if your breakthrough pain isn't relieved after you use Subsys (fentanyl).
Wait at least 4 hours before treating another episode of breakthrough pain.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Not taking around-the-clock opioids (opioid non-tolerance)
Short-term pain, such as headache, migraine, dental pain, or pain after surgery
Severe asthma
Stomach or intestinal blockage (paralytic ileus)
Allergy to other fentanyl products
By signing up, I agree to GoodRx's Terms and Privacy Policy, and to receive marketing messages from GoodRx.
American Cancer Society. (2024). Pain in people with cancer.
Centers for Disease Control and Prevention. (2022). About opioid use during pregnancy.
Insys Therapeutics, Inc. (2021). Subsys [package insert]. DailyMed.
Jansson, L. M., et al. (2019). Neonatal abstinence syndrome. Pediatric Clinics of North America.
McNicol, E., et al. (2003). Management of opioid side effects in cancer-related and chronic noncancer pain: A systematic review. The Journal of Pain.
National Institute of Diabetes and Digestive and Kidney Diseases. (2018). Adrenal insufficiency & Addison’s disease.
National Institute of Diabetes and Digestive and Kidney Diseases. (2018). Symptoms & causes of adrenal insufficiency & Addison's disease.
Taylor D. R. (2013). Single-dose fentanyl sublingual spray for breakthrough cancer pain. Clinical Pharmacology: Advances and Applications.
U.S. Food and Drug Administration. (2020). Questions and answers: FDA approves a class Risk Evaluation and Mitigation Strategy (REMS) for transmucosal immediate-release fentanyl (TIRF) medicines.
Research prescriptions and over-the-counter medications from A to Z, compare drug prices, and start saving.