Do Not Use Fentanyl for Non-Cancer Pain

In September 2017, The New York Times reported on new data from the federal government on the number of deaths from drug overdoses in recent years. The figures were staggering: drug overdose deaths increased 22 percent from 2015 to 2016. The single drug involved in the most deaths (20,000 of 64,000 total overdose deaths in 2016) and the greatest increase in overdose deaths (540% increase from 2014 to 2016) in recent years was the opioid fentanyl in both its prescribed (ABSTRAL, ACTIQ, DURAGESIC, FENTORA, IONSYS, LAZANDA, SUBLIMAZE, SUBSYS) and illicit forms. This is not surprising given that fentanyl is extremely potent and therefore can be lethal at even very low doses.

About fentanyl

Fentanyl is a synthetic opioid. It was originally used for anesthesia and only later for pain relief at low doses. It is extremely potent, approximately 50-100 times more so than morphine.

Most prescription versions of fentanyl — Abstral, Actiq, Fentora, Lazanda and Subsys — are approved by the Food and Drug Administration (FDA) only for cancer patients suffering from bouts of acute “breakthrough” pain who are already receiving around-the-clock opioid therapy for persistent cancer pain. They are approved only for cancer patients who are considered “opioidtolerant”: patients who have already been on sufficient doses of other opioids for at least a week and whose bodies are therefore adjusted to the potent effects of opioids.

Two other versions of fentanyl are approved by the FDA for use only in a hospital or other inpatient setting for acute post-surgical pain relief (Ionsys) or anesthesia (Sublimaze). Only one formulation of fentanyl, the Duragesic skin patch, is approved for outpatient use for pain in noncancer patients for whom alternative treatment options are inadequate or not tolerated.

Studies of fentanyl

There is no doubt that fentanyl is effective for treating pain in opioidtolerant cancer patients at low doses and, for some cancer patients, when used as indicated, can result in fewer minor adverse effects, such as nausea, vomiting, constipation, dry mouth, dizziness and sleepiness, than other, less potent opioids. However, because of its potency, fentanyl also can result in fatal respiratory depression at relatively low doses, especially in patients whose bodies are not used to opioids (known as “opioid-naïve” patients). Fentanyl has a lengthy list of other side effects, including the following listed in a black-box warning on the drug’s label:

• Potentially fatal if accidentally ingested, especially by children
• Potentially fatal drug-drug interaction with many oral or injectable drugs, including benzodiazepines (for example, alprazolam [XANAX]), erythromycin (E.E.S., ERY-TAB, ERYC, ERYPED, PCE), anti-fungal drugs (for example, ketoconazole [generic only]), protease inhibitors for HIV infection (for example, ritonavir [KALETRA, NORVIR, TECHNIVIE, VIEKIRA]), rifampin (RIFADIN, RIFAMATE, RIFATER, RIMACTANE), carbamazepine (CARBATROL, CARNEXIV, EPITOL, EQUETRO, TEGRETOL, TERIL) and phenytoin (DILANTIN, PHENYTEK)
• Addiction, abuse and misuse
• If used during pregnancy, risk of potentially fatal newborn opioid withdrawal syndrome

Other risks of fentanyl are serotonin syndrome if used with certain serotonergic drugs (for example, the antidepressant fluoxetine [PROZAC, SARAFEM, SELFEMRA]), adrenal gland failure, severely low blood pressure, worsening swelling of the brain and surrounding tissues, bowel or bile duct obstruction, increased risk of seizures in patients with epilepsy, impairment of ability to drive and engage in other hazardous activities, and slow heart rate.

For non-cancer patients, there is no acceptable evidence that fentanyl or any other opioid is effective for the long-term relief of chronic pain conditions in either adults or children. Regardless of whether fentanyl is effective for the long-term relief of pain in non-cancer patients, however, its serious risk of death at very low doses and the existence of safer alternatives for pain management (including less potent opioids) mean that its use in non-cancer patients is not warranted.

Overdose epidemic: Fentanyl largest contributor

Fentanyl’s role in the opioidoverdose epidemic has been relatively recent, involved in just 3,000 drug overdose deaths in 2014 but 20,000 (nearly one-third of all drug overdose deaths in the U.S.) in 2016. Many of these deaths involved illegal versions of fentanyl increasingly being mixed with heroin sold on the black market. However, legally (but likely inappropriately in many cases) prescribed fentanyl also has played a major role in ensuring an ample supply of the drug, with 4.6 million prescriptions dispensed in the first nine months of 2016. Fentanyl obtained from a physician can be illegally diverted for street sale. In addition, many patients prescribed fentanyl have overdosed on the drug.

What You Can Do

Do not use fentanyl unless you are a cancer patient with breakthrough, cancer-related pain, are considered opioid-tolerant and are able to take the drug exactly as prescribed and under the close supervision of your doctor.

Refernces

[1] Katz J. The first count of fentanyl deaths in 2016: Up 540% in three years. September 2, 2017. The New York Times. https://www.nytimes.com/interactive/2017/09/02/upshot/fentanyl-drug-overdose-deaths.html?_r=0. Accessed December 8, 2017.

[2] Bond A. Why fentanyl is deadlier than heroin, in a single photo. STAT. September 29, 2016. https://www.statnews.com/2016/09/29/fentanyl-heroin-photo-fatal-doses/. Accessed December 8, 2017.

[3] Centers for Disease Control and Prevention. Fentanyl. August 29, 2017. https://www.cdc.gov/drugoverdose/opioids/fentanyl.html. Accessed December 8, 2017.

[4] Sentynl Therapeutics. Label: fentanyl sublingual tablets (ABSTRAL). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022510s015lbl.pdf. Accessed December 8, 2017.

[5] Teva Pharmaceuticals. Label: fentanyl oral transmucosal lozenge (ACTIQ). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022510s015lbl.pdf. Accessed December 8, 2017.

[6] Teva Pharmaceuticals. Label: fentanyl buccal tablet (FENTORA). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021947s019lbl.pdf. Accessed December 8, 2017.

[7] Depomed. Label: fentanyl nasal spray (LAZANDA). March 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022569s024lbl.pdf. Accessed December 8, 2017.

[8] Insys Therapeutics. Label: fentanyl sublingual spray (SUBSYS). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202788s016lbl.pdf. Accessed December 8, 2017.

[9] The Medicines Company. Label: fentanyl iontophoretic transdermal system (IONSYS). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021338s007lbl.pdf. Accessed December 8, 2017.

[10] Akorn. Label: fentanyl citrate injection (SUBLIMAZE). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/016619s038lbl.pdf. Accessed December 8, 2017.

[11] Janssen Pharmaceuticals. Label: fentanyl transdermal system (DURAGESIC). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019813s069lbl.pdf. Accessed December 8, 2017.

[12] Hadley G, Derry S, Moore RA, Wiffen PJ. Transdermal fentanyl for cancer pain. Cochrane Database Syst Rev. 2013 Oct 5;Issue 10:CD010270.

[13] Wiffen PJ, Derry S, Moore RA. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain. Cochrane Database Syst Rev. 2014 May 29;Issue 5:CD011056.

[14] Bond A. Why fentanyl is deadlier than heroin, in a single photo. STAT. September 29, 2016. https://www.statnews.com/2016/09/29/fentanyl-heroin-photo-fatal-doses/. Accessed December 8, 2017.

[15] Sentynl Therapeutics. Label: fentanyl sublingual tablets (ABSTRAL). December 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022510s015lbl.pdf. Accessed December 8, 2017.

[16] Katz J. The first count of fentanyl deaths in 2016: Up 540% in three years. September 2, 2017. The New York Times. https://www.nytimes.com/interactive/2017/09/02/upshot/fentanyl-drug-overdose-deaths.html?_r=0. Accessed December 8, 2017.

[17] Lewis N, Ockerman E, Achenbach J, Lowery W. Fentanyl linked to thousands of urban overdose deaths. August 15, 2017. The Washington Post. https://www.washingtonpost.com/graphics/2017/national/fentanyl-overdoses/?utm_term=.8f1c62ad8227. Accessed December 8, 2017.

[18] Drug Enforcement Administration. Diversion Control Division. FENTANYL. December 2016. https://www.deadiversion.usdoj.gov/drug_chem_info/fentanyl.pdf. Accessed December 8, 2017.