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Boxed warnings

Fentanyl has various boxed warnings to alert users and doctors about its dangerous side effects.¹

Addiction and misuse warning

People taking fentanyl face a risk of misuse, abuse, and addiction, resulting in overdose and death.

Serious respiratory depression

Fentanyl can cause patients to breathe more slowly, leading to breathing failure. The risk is highest among people who are older, have lung disease, or take other medications that may affect breathing. Your doctor will monitor closely for this condition during initiation and after a dose increase.

Heat exposure warning

For people using the fentanyl transdermal system, exposing the application site or the surrounding areas to direct external heat sources can increase the body’s absorption of fentanyl, potentially leading to a fatal overdose.

Neonatal opioid withdrawal syndrome

Long-term use of fentanyl during pregnancy can result in neonatal opioid withdrawal syndrome, a condition in which an infant born to a mother taking opioids experiences withdrawal symptoms. This syndrome can be life-threatening if not treated.

Accidental exposure warning

Accidental exposure to fentanyl, particularly in children, can lead to a fatal overdose.

Warning against the use of fentanyl with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers while taking fentanyl)

Interactions between the drugs can result in a fatal overdose.

Warning against the use of fentanyl with benzodiazepines or other central nervous system depressants, including alcohol

Combining fentanyl with central nervous system depressants may result in severe sedation, respiratory depression, coma, and death.

Conditions fentanyl treats:

Fentanyl is approved for use in the following situations:² ³

  • Pain control before or immediately after surgery

  • As an anesthesia adjunct

  • To induce general anesthesia

  • As an analgesic in opioid-tolerant patients whose pain is severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

What is fentanyl?

Fentanyl is an exceptionally powerful analgesic belonging to a class of pain drugs called synthetic opioids. It is prescribed for the management of severe pain only in specific situations, as it is up to 100 times stronger than morphine and 50 times stronger than heroin. While its value in appropriate medical cases is undeniable, the drug’s powerful opioid properties also mean there’s a significant risk for misuse, abuse, and overdose-related deaths.⁴

What is fentanyl used to treat?

Fentanyl is used for severe pain management in medical situations such as major surgeries. Additionally, it’s prescribed to help with breakthrough pain, particularly in people with cancer who have severe pain demanding around-the-clock treatment and where other pain medications have failed to provide adequate relief or in cases where the patient is allergic or intolerant to other pain medications. It is also valuable in treating severe chronic pain in patients who are physically tolerant to other opioids.

Fentanyl is highly addictive. Of course, the risk of addiction is much higher in people who misuse the drug, but addiction develops even in people taking the drug precisely as prescribed. Hence, it is reserved exclusively for particular pain management cases when no other alternative is sufficient, and after thorough evaluation by the physician for misuse, addiction, or overdose risk, with continuous close monitoring for any mental, physical, or behavioral changes during the course of treatment.⁵

Dosage forms and strengths

Fentanyl comes in different forms and a range of strengths, as detailed below:⁶

  • Sublingual tablets: 100–800 micrograms (mcg)

  • Nasal spray: 100–400mcg

  • Patches for direct-to-skin application: Release rate of 12–100mcg/hr⁷

  • Lozenges: 200–1,600mcg

  • Injections: A single concentration of 50mcg/mL (0.05mg/mL)⁸

It’s essential to note that the different forms of fentanyl are not interchangeable. Do not switch forms without consulting your prescriber. If you decide to change from one type to another, you must do so under close medical supervision.

How do you take fentanyl?

How you take fentanyl will depend on the form.

If you take fentanyl lozenges, place the lozenge in your mouth between your cheek and gum. You can suck on the medication but don’t crush, chew, or bite it. Don’t eat or drink anything until the lozenge disappears.⁹

If you use buccal tablets, place the tablet above a rear molar tooth, between your cheek and gum. This space is called the buccal cavity. You may feel a gentle bubbling sensation as the tablet dissolves. Do not crush or chew the tablet. If any part of the tablet remains after 30 minutes, you can swallow it with a glass of water.¹⁰

If you opt for sublingual tablets, place the tablet under your tongue and wait for it to dissolve. Do not chew the tablet or swallow it whole, and don’t eat or drink anything until the tablet has dissolved completely.¹¹

The fentanyl patch must be applied to dry, flat skin. Doctors usually recommend placing it on the upper arm, chest, or back. Be sure to avoid exposing the application site to external heat, as excessive heat can affect the delivery of the drug and lead to an overdose. Wash your hands immediately after applying the patch.¹²

To use the sublingual spray form, hold the unit upright and point the nozzle under your tongue. Squeeze the unit to spray the medication and keep it under your tongue for 30–60 seconds. This type is not to be confused with the nasal spray, which is administered by inserting the tip a short distance into the nostril and depressing the applicator.¹³ ¹⁴

Fentanyl injections are administered by a qualified healthcare provider in a medical setting.

How often you take fentanyl depends on the type. For instance, tablets, lozenges, and nasal sprays are fast-acting. As such, you should use them as needed but no more than four times daily.¹⁵

In contrast, patches release the medication slowly over time, making them useful for long-lasting pain. You'll need to apply a new patch every three days, and you must remove the previous patch before applying the current one.

Typically, doctors prescribe a low dose of fentanyl and slowly increase the amount as needed. The continuing dose is usually set at the lowest amount that provides adequate pain relief.

Seeing results

Injections are the fastest-acting form of fentanyl and work almost immediately. Other fast-acting forms, including tablets, lozenges, and nasal sprays, take around 15–30 minutes to start working and can last up to 4–6 hours.¹⁶

Patches are gradually released into the body through the skin and may take days to produce results, but the effects last longer than tablets. When starting treatment with fentanyl patches, your doctor may prescribe a tablet to help manage the pain until the patch begins working.¹⁷

Who should not take fentanyl?

Fentanyl is not suitable for everyone. Tell your doctor before starting this drug if you:¹⁸

  • Have had an allergic reaction or are intolerant to fentanyl or any other opioids

  • Have irregular heartbeats (arrhythmia)

  • Have low blood pressure

  • Have a head injury or condition that causes fits or seizures

  • Have adrenal gland problems

  • Have kidney or liver problems

  • Have any lung conditions or asthma

  • Have ever misused or abused prescription medications, alcohol (including heavy drinking), or used illicit drugs

  • Are trying to conceive, are pregnant, or breastfeeding

Caution is necessary when using fentanyl in young children and the elderly, as they may be more sensitive to the drug's effects.

Potential side effects of fentanyl

Fentanyl is approved by the US Food and Drug Administration (FDA) and prescribed by doctors in particular situations where there are no other effective treatment options and because the benefits likely outweigh the risks. However, like all medicines, fentanyl can trigger side effects.

Common side effects of fentanyl include:¹⁹

  • Constipation

  • Feeling or being sick (nausea or vomiting)

  • Stomach pain

  • Feeling sleepy or tired

  • Feeling dizzy or a sensation of spinning (vertigo)

  • Confusion

  • Headaches

  • Mild irritation, itching, or redness at the application site

Most of these side effects are more likely to occur when you first take the drug or with higher doses of fentanyl. Some may improve or resolve after using the medicine for some time; however, if side effects persist or worsen, consult your doctor. 

Other side effects can be severe and require immediate medical attention. Possible severe side effects include:²⁰

  • Changes in heartbeat

  • Difficulty breathing

  • Extreme drowsiness

  • Agitation, hallucinations, or confusion

  • Irregular menstruation

  • Decreased sexual desire

  • Seizures

  • Severe muscle stiffness

  • Hives

While some of these side effects may seem minor, they can indicate severe underlying issues.

In addition to the side effects linked to proper use, misusing or abusing fentanyl can have serious consequences, including:

  • Overdose

  • Severe respiratory depression

  • Neonatal opioid withdrawal syndrome

  • Dangerous drug interactions

Navigate to the Boxed warnings section above for more information on adverse effects.

These lists of potential side effects are not exhaustive. If you notice anything unusual while taking fentanyl (or any other medication), consult your doctor.


Overdoses of fentanyl are not rare. While overdose is much more common among people who misuse or abuse the drug, overdose can occur in people taking the medication as prescribed. Due to its high potency, fentanyl is one of the leading contributors to drug overdose deaths in the US.²¹

Recognizing signs of an overdose can save lives. Signs to look out for include:²² ²³

  • Difficulty breathing or stopping breathing

  • Slow, shallow breathing

  • Smaller pupils (the black circles in the middle of the eyes)

  • Dizziness

  • Drowsiness, sleepiness, or losing consciousness

  • Extreme lethargy

  • Skin that feels cold and clammy

  • Confusion

If you suspect an overdose, call 911 immediately. If you take fentanyl or care for someone who does, consider carrying naloxone. This drug blocks the effects of fentanyl to limit dangerous symptoms caused by high levels in the blood. You can buy naloxone from any pharmacy without a prescription.

Allergy information

Call 911 or visit the nearest emergency room if you experience any of the following signs of a drug allergy:

  • A skin rash that includes red, swollen, blistered, itchy, or peeling skin

  • Trouble breathing or speaking

  • Swelling in the mouth, face, lips, or throat

  • Tightness in the chest or throat

  • Wheezing

Long-term use of fentanyl

If you have a condition that demands long-term pain relief, you may need to take fentanyl for a long time. Unfortunately, prolonged use typically increases the risk of developing serious side effects. Additionally, your body can build tolerance to the drug, resulting in more frequent use or higher doses to achieve adequate relief, increasing the risk of addiction or overdose.

Fentanyl in pregnancy and breastfeeding

Fentanyl is a pregnancy category C drug. There are no adequate studies in humans, but animal studies indicate risks of reduced fetal survival rates and developmental delays. Your physician may decide your situation warrants use during pregnancy. If that’s the case, your doctor may prescribe fentanyl for one-time treatment or a short period to reduce the risk of neonatal opioid withdrawal syndrome.²⁴

Neonatal opioid withdrawal syndrome, which results in withdrawal symptoms in the infant, can result from prolonged use or use in the late stages of pregnancy. Further, fentanyl is known to cross the placental barrier and may result in respiratory depression and psycho-physiologic effects in newborns. It may also reduce the strength, duration, and frequency of uterine contractions, thus prolonging labor. Therefore, the drug is not recommended near delivery.²⁵

Fentanyl is also not recommended during breastfeeding because it's present in breast milk. Your newborn may experience severe side effects, such as excess sedation and respiratory depression. Your baby may also become physically dependent on this drug and later experience withdrawal, which can be life-threatening.

Let your doctor know if you’re pregnant, breastfeeding, or trying to conceive. 

Missed doses

If you miss a dose of fentanyl, speak with your doctor. 

In general, fentanyl tablets, sprays, and lozenges are used as needed for acute pain, so it's unlikely you'll miss a dose.

However, if you use fentanyl patches, you may forget to change a patch on time (usually on the third day). If that’s the case, simply remove and replace the patch as soon as you remember.

Never double a dose of fentanyl or take two doses close in time to each other to make up for the missed one, as this can increase your risk of an overdose and death. If it's nearly time for your next dose, skip the missed one.

Drug interactions

Fentanyl can interact with other drugs, and the interactions may be fatal. So before you take fentanyl, let your doctor know if you use any of the following drugs (even occasionally). Similarly, if you’re taking fentanyl and plan to start a new medication, ask your doctor if it’s safe. Drugs and substances that may interact with fentanyl include:²⁶

  • Other opioid pain or cough relievers

  • Sedatives, including valium, lorazepam, temazepam, and others

  • Other drugs that cause drowsiness or slow breathing

  • Muscle relaxants

  • Certain antibiotics, including erythromycin and clarithromycin

  • Certain antifungals, such as ketoconazole

  • HIV medications, such as protease inhibitors (including ritonavir)

  • Benzodiazepines, such as alprazolam

  • Cold or allergy medications

  • Monoamine oxidase inhibitors (MAOIs) — do not take fentanyl for at least 14 days after you stop taking MAOIs, and do not take them concurrently

  • Drugs affecting serotonin levels in the body

  • Grapefruit juice

  • Alcohol

This is not an exhaustive list of all possible dangerous interactions. If you’re taking any medications, supplements, or herbs, ask your doctor if you can continue when you start treatment with fentanyl.

Can I drink alcohol while taking fentanyl?

Avoid drinking alcohol or using other central nervous system depressants while taking fentanyl. Interactions with these substances may increase fentanyl levels in the body, which could result in respiratory depression or a fatal overdose.²⁷

What to discuss with your doctor before starting fentanyl

Tell your doctor about prescription drugs, over-the-counter medicines, herbs, and supplements you take regularly or occasionally.

Let your doctor know if you're allergic to any of the ingredients in fentanyl or have ever had an unusual reaction to other opioids or painkillers.

Inform your doctor of your complete medical history, including any physical or mental health conditions you currently have or have struggled with in the past.

Given the highly addictive nature of fentanyl, you must let your doctor know if you or anyone in your family struggles with any type of addiction.

Fentanyl may affect libido and fertility. Speak with your doctor if you’re concerned.²⁸

Ask your doctor about steps you can take to reduce the risk of unwanted side effects. You may be able to adjust your diet to combat constipation, for example.

And finally, let your doctor know if you’re pregnant, breastfeeding, or trying to conceive.

Stopping fentanyl

Stopping this medication after high doses or long-term use can be challenging. You may experience withdrawal symptoms when you stop taking it abruptly. If you've been taking fentanyl for a while, don't stop without talking to your doctor. Your doctor can guide you in stopping fentanyl gradually and safely.

Drug approval history²⁹

  • 1959: Fentanyl is first synthesized³⁰

  • 1968: Initial US FDA approval for the injectable form

  • 1990: The US FDA approves the fentanyl transdermal patch (Duragesic), the first formulation of an opioid patch

  • 1998: Actiq lozenges are approved with restricted distribution to prevent accidental exposure in children and misuse due to the drug’s lollipop-like appearance

  • 2006: The US FDA approves fentanyl buccal tablets under the brand name Fentora

  • 2009: Onsolis, a buccal soluble film, is granted approval (since discontinued)

  • 2011: The US FDA approves Abstral sublingual tablets and Lazanda nasal spray

  • 2012: Susbsys sublingual spray gains approval

Tips for taking fentanyl

The following tips can help you take fentanyl safely:

  • Use fentanyl precisely as directed, do not take more than prescribed, change your schedule, or start taking other medications without consulting your doctor.

  • Know how to recognize and react to an overdose.

  • Keep naloxone nearby in case of an overdose.

  • Do not apply the patch on burns, cuts, irritated skin, or skin that has been exposed to radiation.

  • Do not expose the patch site or the surrounding area to heat.

  • Don't share your medication with others, even if you have the same symptoms.

  • Keep a written list of all the drugs you take regularly or occasionally.

  • Keep this medicine (and others) out of reach of children.

Frequently asked questions

How does fentanyl make you feel?

Fentanyl binds to the opioid receptors in the central nervous system, thus blocking pain signals to the rest of the body. It affects people differently. Possible effects include feeling extremely relaxed, happy, drowsy, nauseous, and dizzy.

What is stronger than fentanyl?

The US FDA has approved sufentanil sublingual tablets and injections. This medication is more potent than fentanyl (its analog). But, of course, with the higher potency comes a higher risk for misuse, abuse, addiction, and overdose.³¹ ³²

How strong is fentanyl?

This opioid medication is up to 50 times stronger than heroin and up to 100 times stronger than morphine. It's one of the most significant contributors to fatal overdoses in the US.³³

  1. Duragestic (fentanyl transdermal system), CII (2019)

  2. Fentanyl citrate injection, for intravenous or intramuscular use, CII (2019)

  3. Duragestic (fentanyl transdermal system), CII (2019)

  4. Drug fact sheet: Fentanyl | Drug Enforcement Administration

  5. Duragestic (fentanyl transdermal system), CII (2019)

  6. Fentanyl transmucosal (Rx) | Medscape

  7. Duragestic (fentanyl transdermal system), CII (2019)

  8. Fentanyl citrate injection, for intravenous or intramuscular use, CII (2019)

  9. Fentanyl citrate lozenge | NIH: DailyMed

  10. Fentanyl buccal- fentanyl citrate tablet | NIH: DailyMed

  11. Abstral- fentanyl citrate tablet | NIH: DailyMed

  12. Fentanyl patch | NIH: DailyMed

  13. Fentanyl sublingual spray | NIH: MedlinePlus

  14. Lazandra- fentanyl spray | NIH: DailyMed

  15. Fentanyl | NIH: MedlinePlus

  16. Fentanyl citrate injection, solution | NIH: DailyMed

  17. Fentanyl patch | NIH: DailyMed

  18. Duragestic (fentanyl transdermal system), CII (2019)

  19. (As above)

  20. (As above)

  21. Drug fact sheet: Fentanyl | Drug Enforcement Administration

  22. (As above)

  23. Fentanyl | NIH: MedlinePlus

  24. Abstral® (fentanyl) sublingual tablets CII (2011)

  25. Duragestic (fentanyl transdermal system), CII (2019)

  26. Fentanyl citrate injection, for intravenous or intramuscular use, CII (2019)

  27. Duragestic (fentanyl transdermal system), CII (2019)

  28. (As above)

  29. Timeline of selected FDA activities and significant events addressing substance use and overdose prevention | U.S. Food and Drug Administration

  30. Drug fact sheet: Fentanyl | Drug Enforcement Administration

  31. FDA goes ahead with approval of sufentanil despite controversy | Medscape

  32. Sufentanil citrate injection, USP CII (2014)

  33. Fentanyl facts | Centers for Disease Control and Prevention (CDC)

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Here at HealthMatch, we’ve done our best to ensure that the information provided in this article is helpful, up to date, and, most importantly, accurate.

However, we can’t replace the one-to-one advice of a qualified medical practitioner or outline all of the possible risks associated with this particular drug and your circumstances.

It is therefore important for you to note that the information contained in this article does not constitute professional medical or healthcare advice, diagnosis or recommendation of treatment and is not intended to, nor should be used to, replace professional medical advice. This article may not always be up to date and is not exhaustive of all of the risks and considerations relevant to this particular drug. In no circumstances should this article be relied upon without independent consideration and confirmation by a qualified medical practitioner.

Your doctor will be able to explain all possible uses, dosages, precautions, interactions with other drugs, and other potential adverse effects, and you should always talk to them about any kind of medication you are taking, thinking about taking or wanting to stop taking.

Curious about clinical trials?

Access the latest treatments and medications. unavailable elsewhere - entirely free of charge. We make it easy to take part.