Fentanyl: America's Most Dangerous Drug?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on April 14, 2021.

• Care Notes
• Medication List

• Generic name: fentanyl (FEN ta nil)
• Brand names: Actiq, Duragesic, Fentora, Lazanda, Sublimaze, Subsys 
• Street names: Apace, China Girl, China White, China Town, Dance Fever, Friend, Goodfellas, Great Bear, He-Man, Jackpot, Murder 8, Poison, and Tango & Cash

Dangerous prescription opioids are no longer just limited to oxycodone or hydrocodone. As reported by the U.S. Centers for Disease Control (CDC), deaths involving synthetic opioids which primarily involved fentanyl accounted for more than 36,359 overdose deaths in 2019. 

2019 Report: CDC: Fentanyl Overdose Deaths Are Soaring

Fentanyl is a legal prescription drug used for pain control during surgery and for chronic or breakthrough cancer pain. It's also being manufactured illegally and sold for its euphoric effects.

Street drugs like heroin, cocaine and methamphetamine are being laced with this opioid, as are counterfeit drugs made to look like the real ones, like hydrocodone tablets or Xanax. It’s an extremely potent and rapidly fatal substitute for heroin.

• Fentanyl works in the brain to block pain and is in the same class of drugs as morphine or hydrocodone but is about 50 to 100 times more potent.
• Just 2 to 3 milligrams of this drug can lead to death. It blocks opioid receptors and its most dangerous side effect -- like other opioids --  is respiratory depression, which can quickly lead to coma and death.
• Users may not realize the street drug they are buying from a dealer contains this potentially lethal compound.

Fentanyl history

Timeline of fentanyl development in the U.S.

• 1959-1960: First developed by Janssen as an intravenous (IV) surgical anesthetic.
• 1968: Fentanyl citrate (Sublimaze) is FDA-approved and enters general medical use in the US. A preservative-free injectable formulation is still available on the market.
• 1990: Duragesic, an extended-release transdermal film is developed. This widely used product is a long-acting fentanyl patch applied to the skin to treat severe, ongoing pain, such as breakthrough cancer pain in patients who have already used and are tolerant to opioids.
• 1998: Actiq, an oral transmucosal lozenge is approved to treat breakthrough cancer in patients who are opioid tolerant. Actiq is sometimes referred to as an Actiq or fentanyl "lollipop".
• 2006: Fentora, a effervescent buccal tablet is FDA-approved for opioid-tolerant cancer patients. Ionsys, an iontophoretic transdermal system was also approved in 2006 but was voluntarily removed from the market in 2017.
• 2009: Onsolis, a buccal film (dissolved between the cheek and gum) was approved in 2009 for cancer pain, but was discontinued in 2011. Onsolis is now discontinued from the US market.
• 2011: Abstral sublingual tablets and Lazanda intranasal spray are approved, both for breakthrough pain in opioid-tolerant cancer patients. Abstral no longer available in US market. 
• 2012: Subsys, a sublingual spray formulation is approved for the treatment of breakthrough cancer pain in opioid-tolerant patients.

Formulations and uses of fentanyl

Many approved prescription dose forms are available: injection, transdermal patch, oral sublingual tablet or transmucosal lozenge, and nasal or oral spray. Approved generics of some formulations are available.

Table 1. Fentanyl Brands in the U.S.

Brand	Strengths* / Dosage Form	Manufacturer
Abstral (brand discontinued)	100, 200, 300, 400, 600, 800 mcg sublingual (under the tongue) tablet	Sentynl Therapeutics
Actiq	200, 400, 600, 800, 1200, 1600 mcg oral transmucosal lozenge ("lollipop")	Cephalon
Duragesic	12, 25, 50, 75, 100 mcg/hour transdermal system (fentanyl skin patch)	Janssen Pharmaceuticals
Fentora	100, 200, 400, 600, 800 mcg effervescent buccal tablet (placed in cheek/gum area)	Cephalon
Ionsys (discontinued)	40 mcg/activation iontophoretic transdermal system	The Medicines Company
Lazanda	100, 300, 400 mcg/spray nasal spray	BTCP Pharma
Onsolis (brand discontinued)	200, 400, 600, 800, 1200 mcg buccal film (placed in cheek/gum area)	BDSI
Sublimaze Preservative- Free	50 mcg/mL (base form) injection	Akorn
Subsys	100, 200, 400, 600, 800, 1200, 1600 mcg sublingual (under the tongue) spray	BTCP Pharma

^{*mcg = microgram; mcg/hr = micrograms per hour;  the chart does not list recommended doses, dose frequency, or length of time to use the medication. Doses are not equivalent between different dose forms and substitution may be lethal. Only patients who are considered opioid-tolerant (have received certain amounts of opioids within the last week) should use fentanyl. Follow your doctor’s dosing exactly.}

Fentanyl uses

• The oral transmucosal lozenges (Actiq) the effervescent buccal tablets (Fentora), the nasal spray (Lazanda), and the sublingual spray (Subsys) are used for the management of breakthrough cancer pain in patients who have already received opioid medication (are opioid-tolerant) for their underlying persistent pain. 
• Duragesic, the transdermal patch, is used for chronic pain in patients who are opioid tolerant and who require long-term opioid analgesia around the clock and for which other treatments are inadequate. It is not used on an "as-needed" basis.
• Injections (Sublimaze) are administered intravenously (IV) or intramuscularly (IM) by a trained healthcare provider for surgical pain relief and anesthesia uses.
• These products are only used under the immediate supervision of a doctor.

Patients considered opioid-tolerant are those who are taking, for one week or longer, at least 60 mg morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.

Read the Patient Medication Guide that accompanies your medication each time you receive a new prescription. The information may have changed.

Certain oral forms are only available through a program called the Transmucosal Immediate Release Fentanyl (TIRF) Risk Evaluation and Mitigation Strategy (REMS) Access program. To receive these medications you and your doctor will need to participate in this program and use a pharmacy that is part of the TIRF REMS Access program.

Fentanyl abuse and overdose deaths

In 2018 fentanyl was considered the number one opioid killer due to overdose deaths as reported by the CDC. Other opioids have held this dubious position; in 2011, oxycodone (Oxycontin) held the top spot leading to opioid overdose deaths, and from 2012 until 2015 it was heroin.

Duragesic, the patch, can be fatal because high amounts of the drug are retained in the patch after use. The patch can fall off and lead to an overdose if touched. Deaths in children due to accidental exposure have occurred. To lower this risk for children and pets, the FDA states that used patches require proper disposal after use -- fold the patch, sticky sides together, and flush it down the toilet right away.

Related: How to Safely Dispose of Your Old Medications

Drug overdose mortality by state

In a 2018 report from the CDC, the drugs most commonly involved in drug overdose deaths during 2011 to 2016 included fentanyl, heroin, oxycodone, and cocaine. Overdose death rates also accelerated in 2020, possibly due to the stresses of the COVID-19 pandemic.

Table 2. Top 10 Drug Overdoses Ranked by State, CDC 2019

State	Death Rate (%)
West Virginia	52.8
Delaware	48
Ohio	38.3
Maryland	38.2
Pennsylvania	35.6
Connecticut	34.7
Kentucky	32.5
Massachusetts	32.1
New Hampshire	32
New Jersey	31.7

Where does illegal fentanyl come from?

According to the DEA, illegally manufactured fentanyl it is primarily produced in Mexico. 

Do not buy drugs from unverified online pharmacies whether they are foreign or in the states. As noted by the FDA, at any one time there are thousands of illegal websites offering counterfeit drugs to Americans.

Fentanyl use and abuse

Fentanyl side effects (approved product label)

There are many side effects with fentanyl and they can be similar whether the drug is being used legally with a prescription or taken illegally. The risk for detrimental effects may be reduced with a prescription because doses are being selected and monitored by a healthcare provider and you will receive information and education about its use.

However, even if you take your dose correctly as prescribed by your doctor you are at risk for opioid addiction, abuse, and misuse that can lead to death. Call your healthcare provider or emergency responders (911) immediately if you have any severe symptoms.

Common side effects may include: constipation and black, tarry stools, nausea, sleepiness or feeling tired, vomiting, headache, dizziness, stomach pain, low red blood cell count, swelling of the arms, hands, legs and feet, decreased blood pressure, light-headedness or fainting.

Serious side effects may include: extreme drowsiness, heart rhythm changes, chest pain, stiff muscles, trouble walking, high body temperature, swelling of the face, throat, or tongue, confusion, agitation, unconsciousness, respiratory depression (slowed breathing), respiratory arrest (breathing stopped). 

This is not a full list of all possible fentanyl side effects. Call your doctor for more medical advice about side effects. In an emergency, contact a healthcare professional or call emergency personnel (911) immediately.

Related: Fentanyl side effects (in more detail)

Fentanyl effects (abuse and overdose)

People who abuse this opioid do it for the pleasurable effect. When opioid drugs bind to opioid receptors, they boost dopamine levels in the brain's reward areas, causing a state of euphoria or a "high", with relaxation, calm and drowsiness.

Fentanyl is abused by:

• injection
• snorting or sniffing
• smoking
• taking it orally by pill
• spiking it onto blotter paper which is then put in the mouth

Fentanyl patches may be abused by removing the contents and then injecting or ingesting the drug. Patches may also be frozen, cut into pieces, or placed under the tongue or in the cheek cavity.

Like other opioids, the use of this drug, whether legal or illegal, is highly addictive. It can lead to a desire for more drug use, an increase in tolerance, and physical and mental dependence on the drug. Abuse and addiction occurs due to it’s fast action and powerful euphoria.

Overdose may result in: stupor, changes in pupillary size, cold and clammy skin, cyanosis (bluish tint to the skin due to low oxygen levels), coma, and respiratory failure leading to death. The presence of triad of symptoms such as coma, pinpoint pupils, and respiratory depression are strongly suggestive of opioid poisoning.

When fentanyl is being abused the magnitude of the effects are often unpredictable because the amount of drug taken is usually unknown. The presence of unconsciousness or coma, pupil constriction, and respiratory depression (slowed or absent breathing) together strongly suggests an opioid overdose. Contact emergency personnel (911) immediately.

Fentanyl drug interactions

Dangerous drug interactions with fentanyl can occur. Drugs such as other pain medicines, anti-depressant medicines, sleeping pills, anti-anxiety medicines, antihistamines, or tranquilizers may interact and have serious or life-threatening effects. Always tell any doctor you see that you use this drug and have a drug interaction screen before taking any medicine with fentanyl.

Learn More: Review Fentanyl Drug Interactions

How does the DEA classify fentanyl?

Legal prescription opioids, with the exception of certain forms of codeine, are classified as schedule II controlled substances per the U.S. Drug Enforcement Agency (DEA).

Illegal opioids, such as heroin, and black market opioid analogs, or other designer opioids are grouped in schedule I of the Controlled Substances Act. Fentanyl analogs are illegal drugs that are chemically related and designed to mimic its opiate-like effects.

Related: How to Classify Drugs: The Controlled Substances Act

How does fentanyl compare to heroin or other opiates?

Fentanyl is an extremely potent, fully synthetic (man-made) opioid. It is 50 times stronger than heroin and 100 times more potent than morphine. Heroin is derived from morphine, which is a natural substance that is gathered from the opium poppy plant. In contrast, heroin is 2 to 3 times more powerful than morphine. Like heroin, it has a quick onset of action and one dose can be fatal.

Most other opioids are naturally-occurring opiates (codeine, morphine) or are semi-synthetic opiates (oxycodone, hydrocodone) partially derived from opium and part man-made. They are less potent but can still be deadly due to respiratory depression (slowed breathing) if recommended doses are exceeded.

Compared to other prescription opioids, the risk of death is much higher with the abuse of fentanyl due to its relative potency. Errors during illicit production can occur due to the small microgram dose.

In fact, fentanyl is so potent that law officers and first responders are warned to wear protective clothing during known raids to prevent inhalation or skin absorption of the drug.

• The DEA has posted a video, Fentanyl: The Real Deal to provide recommendations to law enforcement and first responders, as well as these safety recommendations for first responders who may encounter the drug.
• Also, review the The National Institute for Occupational Safety and Health (NIOSH) webpage for further details on Preventing Occupational Exposure to Emergency Responders. NIOSH is a division of the CDC.

Why is fentanyl so deadly?

In the outpatient setting for control of cancer pain, fentanyl is only given to patients who are “opioid-tolerant” and have already been taking around-the-clock opioids for severe cancer pain. It’s a strong medication, but when monitored and used as directed by your physician, it can effectively relieve severe pain, and it has an important use in medicine. 

However, when abused or taken in an overdose, this opioid can quickly be fatal because it is so potent. When it's used in combination with other central nervous system depressants like opioids or benzodiazepines, the risk of overdose multiplies. 

Prescription fentanyl is dosed in micrograms, designated by the abbreviation “mcg”. This is an extremely small dose. Most other drugs are dosed in milligrams ("mg"), for example, 500 mg of acetaminophen (Tylenol) or 25 mg of diphenhydramine (Benadryl).

^{Source: DEA, 2018. Two milligrams of fentanyl, a lethal dose in most people.}

What is a microgram?

• One gram is equal 1,000 milligrams. One milligram equals 1,000 micrograms (mcg). So, one microgram is equal to one-thousandth of a milligram or one-millionth of a gram.
• Put another way, one gram is equal to 1,000,000 micrograms.
• One 2 milligram dose of fentanyl is enough to kill an adult.

One reason it is so deadly is that many people are simply unaware of this ongoing threat on the streets. Unsuspecting people are taking adulterated drugs that are laced with fentanyl and becoming the next accidental overdose victim. In 2017, over 59% of opioid-related deaths involved fentanyl compared to 14.3% in 2010, as reported by the NIH.

Fentanyl test strips

Fentanyl test strips are now available that allow those who abuse street drugs like cocaine and heroin to test if their drugs are laced with this product. Once the strip is dipped into a sample of the drug, the results indicate if it's present. Some U.S. programs that distribute clean syringes are also giving out the test strips.

These strips aren't always 100% effective. False positives can occur, and the strips do not quantify the amount of drug that may be present. Also, these strips will not identify newer analogs or other lethal chemicals.

The test strips are also surrounded by controversy: some worry these tests create a false sense of security or justify the use of illegal drugs. It also assumes the user is acting rationally and will avoid use of a drug if it is detected, but this may not always be the case.

Carfentanil: Fentanyl’s more dangerous cousin

While fentanyl is one of the most potent opioids in medicine, it’s not the most potent opioid out there.

An analog known as carfentanil is used exclusively as a tranquilizer in large animal veterinary medicine and is estimated to be 10,000 times more potent than morphine. Carfentanil is often used to tranquilize elephants that can weigh over 15,000 lbs (6800 kg). It has NO medical use in humans.

^{Source: DEA, 2021 Lethal doses of heroin, carfentanil, fentanyl}

Today, this dangerous drug is appearing on the streets, too. Like fentanyl, carfentanil is being cut into other illicit drugs such as heroin or packaged in pills. Street carfentanil first appear in the early 2000s, and there has been an escalation in cases since 2016. A tiny, almost invisible amount of the drug is deadly.

In some cases, heroin has been laced with carfentanil, leading to the death of unsuspecting users. Multiple doses or continuous infusions of the opioid antidote naloxone are needed to reverse effects, which may or may not be successful.

Emergency responders are at risk too. Contamination through the skin, lungs, or mucous membranes by carfentanil can be deadly.

Non-medical and powerful fentanyl analogs such as acetylfentanyl, acrylfentanyl, furanylfentanil and ocfentanil are also fully synthesized and considered illegal. The DEA has identified at least 15 other related compounds. None of the illicitly manufactured analogs are routinely detected in emergency settings because specialized toxicology testing is required.

Another important take-away to consider: even though an online pill identifier might suggest that a pill bought on the street is a legitimate prescription pill because it has the same color and imprint code, this may NOT be true. Illegal drug manufacturers are now creating fake contaminated pills to look exactly like the real ones. You cannot tell if a pill bought off of the street contains a deadly dose of any drug just by looking at it.

Fentanyl withdrawal symptoms

This drug, like other opioids can lead to dependence and withdrawal symptoms whether it is being used legitimately for pain or recreationally. Quickly stopping the drug or even just lowering the dose may lead to withdrawal symptoms.

If you are using medically supervised fentanyl, do not stop it abruptly (“cold turkey”) as this will lead to an opioid withdrawal syndrome. Your doctor will direct you on a careful and slow "taper" of the medication. Tapering is the slow removal of the drug from your body over a set period of time to help lessen the unpleasant effects. If needed, a treatment clinic can start and monitor your safe withdrawal.

Fentanyl withdrawal symptoms:

• overwhelming desire for the opioid
• anxiety, irritability, depression
• difficulty sleeping, or being tired during the day
• nausea and vomiting
• stomach cramps and diarrhea
• sweating or shivering
• muscle aches
• shivering or goosebumps
• yawning
• runny nose and watery eyes

Withdrawal signs and symptoms may begin within 6 to 30 hours after you stop using fentanyl. Symptoms tend to peak at around 36 to 72 hours. By about day 5 to 8 the worst symptoms should begin to subside, but some symptoms, such as a lower tolerance to pain, sleep disturbances, or anxiety, can continue for months.

Once you have stopped using fentanyl, you are at a much greater risk of fatal overdose because your opioid tolerance has decreased. Speak with your doctor or clinic about how to manage cravings that may occur after you have tapered your dose.

Related: Opioid Use Disorder: These Treatments Are Available, Now

There is also a free, national hotline that can be used to help those with drug addiction and mental health needs.

• Call 1-800-662-HELP (4357) for the hotline (in English and Spanish). It is funded by the US Substance Abuse and Mental Health Services Administration (SAMHSA). It is open year-round 24 hours per day.
• Callers can get free and confidential help navigating treatment, finding centers, and directing finances.

Naloxone (Narcan) use for a fentanyl overdose

Naloxone, often sold under the brand name Narcan, is a safe and easily accessible medication used to reverse an opioid overdose and help restore breathing by blocking or reversing the opioid effects.

Use of naloxone for a fentanyl or carfentanil overdose from adulterated pills or heroin off the street paints a different picture. These potent drugs mean that multiple bolus injections of naloxone or even continuous infusions may be needed to reverse the opioid action. Learn how to use naloxone before it is needed.

People at risk for an overdose, or their family members or friends, are encouraged to have naloxone on hand in case of an emergency. It is available in pharmacies and can be acquired without a prescription in most U.S. states.

Speak to your doctor or pharmacist or doctor about this before an emergency occurs. Your doctor should discuss the availability of naloxone with you if you or a family member is prescribed an opioid.

Table 3. Naloxone products

Product Name	Strength / Dose form*	Manufacturer
naloxone injection (generic)	0.4 mg/mL injection	Various
Narcan Nasal Spray (naloxone nasal spray)	4 mg per spray nasal spray, metered dose	Adapt Pharma
Evzio (naloxone autoinjector): discontinued in US	2 mg/0.4mL autoinjector (IM, SC)	Kaleo

• If you believe someone has overdosed, administer naloxone, and then immediately call emergency personnel, such as 911. 
• Naloxone can be life-saving for patients who overdose on narcotics, although in patients dependent upon opioids, it can also cause a severe withdrawal effect.
• If symptoms return, give another dose of naloxone in 2 to 3 minutes. Larger or repeat naloxone doses may be required until emergency responders arrive.

Learn more: What is naloxone?

See Also

• Bath Salts
• Cannabis
• Cocaine
• Devil's Breath
• Ecstasy
• GHB
• Gray Death
• Hashish (Hash)
• Heroin
• Ketamine
• Kratom
• Krokodil
• LSD
• Marijuana
• MDMA (Ecstasy, Molly)
• Mescaline (Peyote)
• Opium
• PCP (Phencyclidine)
• Psilocybin (Magic Mushrooms)
• Quaaludes
• Rohypnol
• Speed (methamphetamine)
• Synthetic Cannabinoids (Synthetic Marijuana, Spice, K2)
• TCP (Tenocyclidine)
• U-47700 (Pink)

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer