Fentanyl

Fentanyl is used to manage breakthrough pain in adults and adolescents 16 years of age and older with cancer who are already routinely taking other opioid pain medicines around-the-clock for cancer pain.

• Oral transmucosal fentanyl preparations or fentanyl nasal spray are not for treating pain that is not cancer-related, such as migraine headaches or pain after surgery.

Fentanyl skin patches may be used when other pain treatments, such as non-opioid pain medicines or immediate-release opioid medicines, do not treat your pain well enough or you cannot tolerate them.

Fentanyl injection is used as a short-acting analgesic before, during, and after surgery and for anesthesia support in general or regional anesthesia or high-risk patients.

Fentanyl is a strong prescription opioid pain medicine that is started only after you have been taking other opioid pain medicines and your body has become used to them (you are opioid tolerant). Do not use fentanyl if you are not opioid tolerant.

An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed, you are at risk for opioid addiction, abuse, and misuse that can lead to death.

Fentanyl was first developed in 1959 and received its initial FDA approval on February 19, 1968. It is a prescription medicine classified as a Schedule II controlled substance under the Controlled Substances Act (CSA).

Because of the risks of addiction, abuse, and misuse, overdose, and death with opioids, which can occur at any dosage or duration and persist over the course of therapy, reserve:

• Transdermal fentanyl for use when other pain treatments, such as non-opioid pain medicines or immediate-release opioid medicines, do not treat pain well enough or are not tolerated
• Transmucosal and nasal fentanyl for use in cancer patients for whom alternative treatment options (such as non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Get emergency help or call 911 right away if you take too much fentanyl (overdose). When you first start taking fentanyl, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse an opioid overdose.

Taking fentanyl with other medicines that may make you sleepy, such as other pain medicines, gabapentinoids (gabapentin or pregabalin), antidepressants, sleeping pills, anti-anxiety medicines, antihistamines, or tranquilizers, or with alcohol or street drugs can cause severe drowsiness, confusion, breathing problems, coma, and death.

Never give anyone else your fentanyl. They could die from taking it. Selling or giving away fentanyl is against the law.

Store fentanyl securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home.

If you stop taking your around-the-clock opioid pain medicine for your cancer pain, you must stop using fentanyl. You may no longer be opioid tolerant. Talk to your healthcare provider about how to treat your pain.

Fentanyl is a powerful synthetic opioid, 100 times stronger than morphine, legally used for severe pain but widely misused. If you have been prescribed fentanyl, take your dose exactly as your healthcare provider tells you to take it. Even patients who have been prescribed fentanyl at the correct dose are at risk of overdose, as the margin between a therapeutic and a fatal dose is narrow.

Illegally manufactured fentanyl (IMF) is frequently mixed into street drugs like heroin and cocaine, often without users' knowledge, making it extremely dangerous. IMF comes in powder, liquid, pills, and even candy form, posing risks to children. Just 2-3 mg can cause fatal respiratory depression.

In 2025, over 76,000 Americans died from fentanyl overdoses. Overdose signs include pinpoint pupils, slow breathing, and loss of consciousness, but are treatable with naloxone (Narcan) if given promptly. Withdrawal symptoms include nausea, anxiety, and muscle pain.

Do not take fentanyl if:

• You are not opioid tolerant. Opioid tolerance means that you are already taking other opioid pain medicines around-the-clock for at least one week or longer for your cancer pain, and your body is used to these medicines.
• You have severe asthma, trouble breathing, or other lung problems.
• You have a bowel blockage or a narrowing of the stomach or intestines.
• You are allergic to any of the ingredients in the formulation.
• You have short-term pain that you would expect to go away in a few days, such as: Pain after surgery Headache or migraine Dental pain.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Before taking fentanyl, tell your healthcare provider if you have a history of:

• Troubled breathing or lung problems such as asthma, wheezing, or shortness of breath
• Head injury, seizures
• Slow heart rate or other heart problems
• Low blood pressure
• Mental problems [including major depression, schizophrenia or hallucinations (seeing or hearing things that are not there)]
• Problems urinating
• Liver, kidney, thyroid problems
• Pancreas or gallbladder problems
• Abuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental health problems
• Diabetes and you are taking fentanyl OTFC (each OTFC unit contains about 1/2 teaspoon [2 grams] of sugar).

Tell your healthcare provider if you are:

• Noticing your pain is getting worse. If your pain gets worse after you take OTFC, do not take more OTFC without first talking to your healthcare provider. Talk to your healthcare provider if the pain you have increases, if you feel more sensitive to pain, or if you have new pain after taking OTFC
• Pregnant or planning to become pregnant. Prolonged use of fentanyl during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated
• Breastfeeding. Fentanyl passes into breast milk and may harm your baby. Carefully observe infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Seek immediate medical care if you notice these signs
• Planning to have children. Using fentanyl for an extended period of time may cause reduced fertility in men and women. It is not known if these effects are reversible.
• Living in a household where there are small children or someone who has abused street or prescription drugs
• Taking certain other prescription over-the-counter medicines, vitamins, or herbal supplements. Taking fentanyl with certain other medicines can cause serious side effects that could lead to death.

The possible side effects of Fentanyl are constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain, weakness, anxiety, depression, rash, and trouble sleeping. Call your healthcare provider if you have any of these symptoms and they are severe.

Fentanyl may cause problems with your esophagus, such as difficulty swallowing, regurgitation, or non-cardiac chest pain. The risk may increase with higher doses or longer use. Tell your healthcare provider if you experience these symptoms.

Fentanyl may also decrease your blood pressure. This can make you feel dizzy or lightheaded if you get up too fast from sitting or lying down.

Fentanyl can cause low blood sugar (hypoglycemia), especially if you have diabetes or other risk factors. Tell your healthcare provider if you experience signs of low blood sugar.

Get emergency medical help or call 911 right away if you have:

• Trouble breathing or shortness of breath
• Fast heartbeat or chest pain
• Swelling of your face, tongue, or throat
• Extreme drowsiness
• Light-headedness when changing positions or feeling faint
• Agitation
• High body temperature
• Trouble walking
• Stiff muscles
• Mental changes such as confusion.

These symptoms can be a sign that you have used too much fentanyl or that the dose is too high for you. These symptoms may lead to serious problems or death if not treated right away. If you have any of these symptoms, do not use any more fentanyl until you have talked to your healthcare provider.

These are not all the possible side effects of fentanyl. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Formulation-Specific Side Effects

Injectable Fentanyl (IV/IM), such as Sublimaze

The most common serious adverse reactions are respiratory depression, apnea, rigidity, and bradycardia. Other reported effects include hypertension, hypotension, dizziness, blurred vision, nausea, vomiting, diaphoresis, pruritus, urticaria, laryngospasm, and anaphylaxis

Fentanyl Transdermal Patch

Possible side effects of the fentanyl transdermal patch (eg, Duragesic) include respiratory depression, sedation, constipation, nausea, and skin reactions at the application site.

Do not expose the patch application site to direct external heat sources such as heating pads, electric blankets, heated waterbeds, tanning lamps, saunas, hot tubs, or hot baths, and avoid exercise that increases your body temperature. This can cause a fatal overdose, as heat significantly increases fentanyl absorption.

If a patch accidentally sticks to a family member while in close contact, take the patch off, wash the area with water, and get emergency help right away because accidental exposure can lead to death or other serious medical problems.

Do not cut, break, chew, crush, dissolve, snort, or inject the fentanyl transdermal patch because this may cause you to overdose and die.

Fentanyl Oral Transmucosal Lozenge (OTFC)

Fentanyl OTFC (eg, Actiq) contains sugar. Cavities and tooth decay can happen in people taking OTFC. When taking OTFC, you should talk to your dentist about proper care of your teeth.

Possible side effects are similar to other transmucosal formulations and include respiratory depression, sedation, nausea, dizziness, and oral mucosal irritation.

Fentanyl Buccal Tablet

The possible side effects of fentanyl buccal or sublingual tablets (eg, Fentora) are similar to other transmucosal formulations, such as respiratory depression, nausea, dizziness, and headache.

Fentanyl Nasal Spray

The possible side effects of fentanyl nasal spray include respiratory depression, nasal irritation, nausea, dizziness, and somnolence.

Fentanyl is available as 2 salts: Fentanyl citrate or Fentanyl hydrochloride.

Fentanyl Citrate

Fentanyl citrate is the most widely used salt across the following multiple formulations:

• Intravenous/intramuscular injection (eg, Sublimaze). Uses: Anaesthesia (premedication, induction, maintenance) and acute severe pain; also used in ICU sedation and in patients with renal failure.
• Oral transmucosal lozenge ("lollipop") (eg, Actiq). Uses: Management of breakthrough pain in opioid-tolerant cancer patients already receiving around-the-clock opioid therapy.
• Buccal tablet (eg, Fentora). Uses: Breakthrough cancer pain in opioid-tolerant patients. Offers slightly improved pharmacokinetics compared to the transmucosal lozenge for the same indication.
• Sublingual tablet (Abstral): Breakthrough cancer pain in opioid-tolerant adults.
• Nasal spray (Lazanda). Uses: Breakthrough cancer pain in opioid-tolerant adults.
• Sublingual spray (Subsys): Breakthrough cancer pain in opioid-tolerant adults.

Fentanyl Base/Hydrochloride

Fentanyl base penetrates the skin more effectively. Formulations include:

• Transdermal patch (Duragesic and generics). Fentanyl base penetrates skin more effectively. Used for chronic pain in opioid-tolerant patients, severe enough to require daily, around-the-clock, long-term opioid treatment where alternative options are inadequate.
• Some compounded injectable preparations use fentanyl hydrochloride.

Fentanyl formulations fall under two REMS programmes. The transdermal patch falls under the general Opioid Analgesic REMS, which focuses on healthcare professional education and patient counselling to reduce addiction, overdose, and death.

The oral transmucosal lozenge (Actiq), buccal tablet, and nasal spray all fall under the more restrictive Transmucosal Immediate Release Fentanyl (TIRF) REMS Access Program. This requires mandatory enrolment of prescribers, patients, pharmacies, and distributors. Patients must speak with their healthcare provider, acknowledge the risks, agree to all programme instructions, and sign a Patient Enrollment Form. Prescriptions can only be filled at TIRF-enrolled pharmacies, which your provider can help locate.

The TIRF programme is significantly more stringent than standard opioid REMS due to the heightened risk of fatal misuse associated with rapid-onset fentanyl formulations.

Do not change your dose. Take oral fentanyl exactly as prescribed by your healthcare provider. Your healthcare provider will change the dose until you and your healthcare provider find the right dose for you.

See the detailed Patient Instructions for Use written in the medication guide for your product for information about how to use your fentanyl preparation.

Fentanyl OTFC

Use 1 unit for an episode of breakthrough cancer pain. Finish the unit over a period of 15 minutes for maximum relief. If you finish OTFC too quickly, you will swallow more of the medicine and get less relief.

• Place OTFC in your mouth between your cheeks and gums and actively suck on the medicine.
• Move OTFC around in your mouth, especially along your cheeks.
• Twirl the handle often.
• Do not bite or chew. You will get less relief for your breakthrough cancer pain.
• You may drink some water before using OTFC, but you should not drink or eat anything while using OTFC.
• If your breakthrough cancer pain is not relieved 15 minutes after you finish the OTFC unit, use only 1 more unit of OTFC at this time.
• If your breakthrough pain does not get better after the second unit of OTFC, call your healthcare provider for instructions. Do not use another unit of OTFC at this time.
• You must not use more than 2 units of OTFC during each episode of breakthrough cancer pain:
• Wait at least 4 hours before treating a new episode of breakthrough cancer pain with OTFC.

You need to keep taking your around-the-clock opioid pain medicine.

Talk to your healthcare provider if your dose of OTFC does not relieve your breakthrough cancer pain. Your healthcare provider will decide if your dose of OTFC needs to be changed.

Talk to your healthcare provider if you have more than 4 episodes of breakthrough cancer pain per day. The dose of your around-the-clock opioid pain medicine may need to be adjusted.

If you begin to feel dizzy, sick to your stomach, or very sleepy before OTFC is completely dissolved, remove OTFC from your mouth.

Do not stop taking OTFC without talking to your healthcare provider. You could become sick with uncomfortable withdrawal symptoms because your body has become used to these medicines. Physical dependency is not the same as drug addiction.

After you stop taking or no longer need OTFC, dispose of it safely. See How do I Dispose of Fentanyl below or visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.

Fentanyl Sublingual Tablets

Place the tablet directly under your tongue, as far back as possible, and allow it to dissolve completely, which usually takes 15 to 25 minutes.

• Do not suck, chew, or swallow the tablet.
• For each breakthrough cancer pain episode, take one dose; if pain persists after 30 minutes, a second dose may be taken.
• No more than 2 doses per episode are permitted, and you must wait at least 2 hours before treating a new episode.
• Continue taking your regular around-the-clock opioid.
• If pain is uncontrolled or episodes exceed 4 per day, consult your healthcare provider. In case of overdose, seek emergency medical help immediately.

Fentanyl Buccal Tablets

Place the tablet in your mouth, between your cheek and gum (buccally) or under the tongue.

• Do not suck, chew, or swallow the tablet.
• For each breakthrough cancer pain episode, take one dose; if pain persists after 30 minutes, a second dose may be taken.
• No more than 2 doses per episode are permitted, and you must wait at least 2 hours before treating a new episode.
• Continue taking your regular around-the-clock opioid.
• If pain is uncontrolled or episodes exceed 4 per day, consult your healthcare provider. In case of overdose, seek emergency medical help immediately.

Fentanyl Nasal Spray

If the bottle hasn't been used for more than 5 days, re-prime it with one spray into the pouch. Before use, confirm the bottle is ready by checking for a green bar or number in the counting window, and blow your nose if needed.

• Sit upright, insert the tip about half an inch into one nostril, pointing toward the bridge of your nose, close the other nostril, and press firmly until you hear a click.
• Breathe in gently through your nose and out through your mouth. If a second spray is prescribed, repeat in the other nostril, alternating nostrils for multiple sprays.
• The counting window increases by one after each spray. When it shows a red "8", the bottle is finished and must not be used again.

Fentanyl Sublingual Spray

Use fentanyl sublingual spray exactly as prescribed. Do not use more than 2 doses for each episode of breakthrough cancer pain. You must wait at least 4 hours before treating a new episode of breakthrough pain.

DO NOT drive or operate heavy machinery until you know how fentanyl affects you. Fentanyl can make you sleepy, dizzy, or lightheaded.

DO NOT drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with fentanyl may cause you to overdose and die.

DO NOT switch from one formulation of fentanyl to another without talking to your healthcare provider. The amount of fentanyl in a dose of some formulations is not the same as the amount of fentanyl in other medicines that contain fentanyl. Your healthcare provider will prescribe a starting dose of fentanyl that may be different than other fentanyl containing medicines you may have been taking.

Unused fentanyl is extremely dangerous and can be fatal to children, pets, and anyone who accidentally comes into contact with it, making prompt and proper disposal essential.

Follow the disposal information below, or you can also safely dispose of fentanyl products by taking them to an authorized drug take-back program or location in your community. To find one near you, contact the DEA at 1-800-882-9539 or visit the US FDA website.

Buccal/Sublingual Fentanyl Tablet Disposal

Unused fentanyl sublingual/buccal tablets should be removed from their blister cards and flushed down the toilet.

• Do not flush the blister cards, packaging, or cartons. These go in the bin.

Oral Transmucosal Fentanyl (OTFC) Disposal

Partially used OTFC units may contain enough medicine to be harmful or fatal to a child or other adults who have not been prescribed OTFC. You must properly dispose of the OTFC handle right away after use, even if there is little or no medicine left on it. Please follow these directions to dispose of the handle:

• Once you have finished the OTFC unit and the medicine is totally gone, throw the handle away in a place that is out of the reach of children.
• If any medicine remains on the handle after you have finished, place the handle under hot running water until the medicine is gone, and then throw the handle away out of the reach of children and pets.
• If you did not finish the entire OTFC unit and you cannot dissolve the medicine under hot running water right away, put the OTFC in the temporary storage bottle that you received in the OTFC Child Safety Kit for safekeeping. Push the OTFC unit into the opening on the top until it falls completely into the bottle. Never leave unused or partially used OTFC units where children or pets can get to them.
• Dispose of the handles in the temporary storage bottle as soon as you can by following the directions in steps 1 and 2. You must dispose of all handles in the temporary storage bottle at least once a day.

Do not flush entire unused OTFC units, OTFC handles, or blister packages down the toilet.

Fentanyl Transdermal Patch Disposal

To dispose of a used or leftover fentanyl patch, fold it in half sticky-side together and flush it down the toilet immediately.

• This is essential as used patches remain dangerous and can be fatal to children, pets, and anyone not prescribed fentanyl.
• Only the patch itself should be flushed. The pouch, protective films, and release liner should be placed in regular household trash.

Fentanyl Nasal Spray Disposal

Dispose of the bottle after 8 sprays have been used or 60 days after first use.

• If doses remain, empty them into the provided pouch by inserting the tip and pressing the grips until the counter reaches "8".
• Once empty, replace the cap, seal the pouch, and place both inside the child-resistant container.
• Close the container and throw it in the bin.
• Wash your hands afterwards.

You may have breathing problems or withdrawal symptoms if you start or stop taking certain other medicines. Tell your doctor if you also use an antibiotic, antifungal medication, heart or blood pressure medication, seizure medication, or medicine to treat HIV or hepatitis C.

Fentanyl can interact with many other drugs and cause dangerous side effects or death. Be sure your doctor knows if you also use:

• other narcotic medications - opioid pain medicine or prescription cough medicine;
• a sedative like Valium - diazepam, alprazolam, lorazepam, Ativan, Klonopin, Restoril, Tranxene, Versed, Xanax, and others;
• drugs that make you sleepy or slow your breathing - a sleeping pill, muscle relaxer, tranquilizer, antidepressant, or antipsychotic medicine;
• cold or allergy medicines, bronchodilator asthma/COPD medication, or a diuretic ("water pill");
• medicines for motion sickness, irritable bowel syndrome, or overactive bladder;
• drugs that affect serotonin levels in your body - medicine for depression, Parkinson's disease, migraine headaches, serious infections, or prevention of nausea and vomiting.

This list is not complete. Other drugs may interact with fentanyl, including prescription and over-the-counter medicines, vitamins, and herbal products. Taking fentanyl with medicines that affect serotonin can cause a rare but life-threatening condition called serotonin syndrome. Seek medical help right away if you develop confusion, hallucinations, fast heartbeat, sweating, muscle stiffness, or shivering. Not all possible interactions are listed in this medication guide.

Always keep fentanyl in a safe place away from children and from anyone for whom it has not been prescribed. Protect fentanyl from theft.

• Some preparations, such as OTFC, have a Child Safety Kit available to help you store OTFC and your other medicines out of the reach of children. If you were not offered a Child Safety Kit when you received your medicine, call 888-534-3119.