Fentanyl: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Jan 3, 2024.

1. How it works

• Fentanyl may be used to treat severe pain that is unresponsive to less potent pain-relieving medicines (analgesics).
• Fentanyl is a full agonist at the mu receptor (full agonists have a larger effect at higher dosages). By binding to these receptors, pain signals are blocked on their way to the brain.
• Fentanyl belongs to the group of drugs known as opioids or opioid analgesics. Fentanyl may also be called a narcotic analgesic.

2. Upsides

• Fentanyl is a very strong pain-relieving medicine used for the relief of moderate-to-severe pain that is unresponsive to less potent pain-relieving medicines.
• Available as an injection, transdermal patch or device, nasal spray, sublingual (under-the-tongue) tablet or spray, or buccal (beneath-the-cheek) lozenges.
• Different formulations have different uses. For example, fentanyl injection may be used as part of anesthesia to help prevent pain after an operation or procedure. Fentanyl patches or transdermal devices may be used for moderate-to-severe pain that requires round-the-clock therapy. Sublingual sprays or tablets may be used for breakthrough-type cancer pain.
• Note that doses are not equivalent between the different formulations (for example a 25mcg fentanyl patch DOES NOT EQUAL 25mcg of fentanyl injection). The substitution of one fentanyl product for a different type of fentanyl product (for example Subsys for Duragesic) may result in a fatal overdose.
• Fentanyl is a pure opioid agonist analgesic. This means that increasing dosages provide increasing pain relief, unlike some other opioids that have a ceiling effect (this means they plateau off above a certain dosage).
• Generic fentanyl is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Nausea, vomiting, constipation, sedation, dizziness, lack of energy, shortness of breath, and abdominal distension.
• May also cause flushing, sweating, itching, red eyes, and a drop in blood pressure on standing.
• Fentanyl is extensively metabolized through the liver when taken orally and as a consequence of this, fentanyl is not available in an oral formulation, although buccal (beneath the cheek) and sublingual (under the tongue) formulations exist. Buccal and sublingual formulations bypass the liver and enter straight into the bloodstream.
• Fentanyl should NOT be used in people who have never been prescribed an opioid analgesic (opioid-naive people).
• Fentanyl is usually only available from a certified pharmacy under a special program.
• Fentanyl is a Schedule II controlled substance and is up to 100 times more potent than morphine on a weight-for-weight basis. Note that different sources cite different equivalent dosages; in reality, there is a wide inter-individual variation between effective opioid dosages. Do not try to convert fentanyl on a weight-for-weight basis (for example from patch to injection using the same mcg dosage) because of an extremely high risk of over-dosage. It is always safer to underestimate fentanyl requirements.
• Because of the risk of addiction and dependence, fentanyl patches should only be used for severe, chronic pain that requires round-the-clock, long-term opioid treatment and for which other treatments have been ineffective. Other forms of fentanyl (such as sublingual spray or tablets) may be used for the relief of breakthrough pain. Fentanyl should not be used for acute or postoperative pain, headaches, or migraines.
• Keep out of the reach of children and pets. Death has been reported in children and pets who have accidentally ingested fentanyl products.
• Fatal breathing problems have occurred in patients given fentanyl products. The risk is higher in those who have not been administered opioids before.
• Fentanyl has a high potential for abuse and care must be taken to keep it hidden from drug seekers. Fentanyl is often used to lace counterfeit drugs - several deaths have been reported, for example, from Xanax laced with fentanyl.
• May interact with other drugs, particularly ones that inhibit the metabolism of fentanyl through CYP3A4, such as ketoconazole, erythromycin, and ritonavir, and those with similar side effects (such as respiratory depression, or sedation). Fentanyl also interacts with other drugs that increase levels of serotonin (such as SSRIs, TCAs, triptans, or tramadol).
• May affect your ability to drive and operate machinery. Avoid alcohol.
• May not be suitable for people with pre-existing respiratory disease, head injuries, bradycardia (slow heartbeat), and other conditions.
• Crosses the placenta and can be detected in neonatal urine 24 hours after maternal epidural administration. Not recommended during pregnancy unless the benefits outweigh the risks. Prolonged use of fentanyl during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. Women should not breastfeed while taking fentanyl.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Fentanyl is a very potent pain-relieving medicine. It is not recommended for people who have never been prescribed opioid-type pain relief before, and deaths have been reported from improper dosing or abuse.

5. Tips

• Ensure you dispose of all fentanyl products (such as used patches or empty spray canisters) carefully as although they may be empty they may still contain enough fentanyl to kill a child or an animal. Many products supply a charcoal-lined pouch in the carton to help with disposal.
• You need to be enrolled in the TIRF REMS Access program before you can receive fentanyl products such as Subsys. In addition, only pharmacies that are enrolled in the TIRF REMS Access program can dispense fentanyl.
• When used for breakthrough pain, NEVER take more than two doses of short-acting fentanyl products (such as Subsys) at one time (each dose must be at least 30 minutes apart).
• Never share your fentanyl with anybody because it may kill them.
• Do not drive or operate machinery if you are sleepy or your reaction time is impaired after taking fentanyl.
• Do not mix fentanyl with alcohol, sleeping aids, or tranquilizers unless prescribed by a doctor.
• Some fentanyl products are provided with a child-safety kit to help adults store them out of reach of children or pets.
• If you are taking sublingual fentanyl, remove a tablet from the blister pack and place it on the floor of the mouth directly under the tongue. Do not chew, suck, or swallow sublingual tablets. Allow the tablet to completely dissolve in the sublingual cavity before eating or drinking anything. If you have a dry mouth, use water to moisten the tissues of the mouth BEFORE taking a sublingual tablet.
• Do not use during pregnancy and breastfeeding unless specifically recommended by your doctor.

6. Response and effectiveness

• Time to effect varies depending on formulation from 15-30 minutes (sublingual tablets), 46 minutes (buccal tablets), 1.5 hours (spray) to 3 hours (patch). Respiratory depressant effects can be seen from as early as 15-30 minutes after administration and persist for several hours.

7. Interactions

Medicines that interact with fentanyl may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with fentanyl. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with fentanyl include:

• anticholinergics, such as atropine, benztropine, or scopolamine
• antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
• anticonvulsants, such as carbamazepine, phenytoin, phenobarbital, or primidone
• antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
• any medication that may cause drowsiness, such as amphetamines, benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine or oxycodone)
• any other medication that increases serotonin levels in the body, such as 5-hydroxytryptophan, antidepressants, migraine medications (such as dihydroergotamine, sumatriptan), tramadol, or St. John's Wort
• buprenorphine
• HIV medications, such as ritonavir
• medications that inhibit hepatic enzymes CYP3A4, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal or grapefruit
• medications that induce hepatic enzymes CYP3A4 such as phenobarbital, phenytoin, rifampicin, St. John's Wort, or glucocorticoids
• muscle relaxants, such as baclofen or cyclobenzaprine.

Avoid drinking alcohol or taking illegal or recreational drugs, including cannabis, while taking fentanyl.

Note that this list is not all-inclusive and includes only common medications that may interact with fentanyl. You should refer to the prescribing information for fentanyl for a complete list of interactions.

References

• Fentanyl lozenges. Updated 02/2023. Mallinckrodt. https://www.drugs.com/pro/fentanyl-lozenge.html
• Fentanyl injection. Updated 02/2023. Mallinckrodt. https://www.drugs.com/pro/fentanyl-injection.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use fentanyl only for the indication prescribed.

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

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