There are news stories every day about the extreme dangers of Fentanyl use in America and no entity feels the effects of that use more than hospitals. A study from the CDC shows that that Fentanyl overdose has grown from 2 percent of the monthly overdose encounters to 12 percent over the last two years. Fentanyl is a schedule two synthetic opioid with specific medical value and a high potential for abuse. Fentanyl was developed in early 1960s so it has been around a long time. It is considered one hundred times more powerful than heroin. The drug provides fast pain relief, but its effects do not last long.
There are specific clinical uses for fentanyl. It is prescribed most often for break through pain in cancer patients that are opioid tolerant or who already use opioid pain medicines regularly. Some of the ways fentanyl can be taken include patches, lollipops, dissolvable tongue film, dissolvable pills and intravenously. Warnings to providers include that it should be prescribed only to patients 18 years of age and older.
Additionally, fentanyl should not be used with certain prescription drugs such as antihistamines, buprenorphine, and many others. When fentanyl is prescribed, physicians should ask about the patient’s family and personal history of alcohol use, illicit drugs, or prescription drugs as well as any mental health issues including depression or hallucinations.
When used illicitly to achieve a high, it is often combined with other drugs to amplify the effects. While the high may be more powerful when drugs are combined, it is also much more dangerous. Federal authorities are warning Americans of an emerging public safety threat, fentanyl mixed with xylazine, a non-opioid agent that the Food and Drug Administration (FDA) originally approved in 1972 as a sedative and analgesic for use in veterinary medicine. (3) The drug is used in large mammals as a sedative and pain reliever.
Structurally xylazine is similar to levamisole, clonidine and tizanidine and may share some clinical effects. Xylazine is not safe for human use and may result in serious and life-threatening side effects that appear to be like side effects commonly associated with opioid use, making it hard to distinguish opioid overdoses with xylazine exposure. Like clonidine, xylazine acts as a central alpha-2- adrenergic receptor agonist in the brainstem, causing a rapid decrease in the release of norepinephrine and dopamine in the central nervous system (CNS). Xylazine may also bind to other CNS receptors, although further research is needed.
Xylazine is mixed with fentanyl, heroin, and other drugs to lengthen their euphoric effects. It is being increasingly detected in fatal overdoses in parts, particularly in the Southern part of the United States. The Drug Enforcement Administration (DEA) has seized fentanyl/xylazine mixtures in 48 of 50 states. (2) The drug is relatively inexpensive and easy for distributors to procure online in the underground market. The increase of xylazine mixed with fentanyl has increased by 8 percent over the last two years.
Xylazine, like fentanyl should not be mixed with other drugs as it can increase the risk of overdose, especially if the other drugs are opioids. It should not be mixed with depressant drugs such as alcohol, benzodiazepines, and tranquilizers. Mixing xylazine with these drugs can lead to drowsiness, sedation, unconsciousness, overdose, and death.
People are often unable to prevent accidental exposure. They are often unaware of the presence or amount of the xylazine in their drug supply. This lack of control over polysubstance exposure leads to overdoses. The acute effects of xylazine which may present in hospital ERs and clinics include:
Chronic effects can include:
Because the tranquilizer xylazine is not an opioid its effects cannot be reversed by the opioid antidote naloxone, also known as Narcan. An FDA alert dated November 8, 2022, states it is unknown if reversal agents regularly used in veterinary medicine, such as yohimbine, hydrochloride and tolazoline hydrochloride are safe or effective in humans, they should not be used. (3) Because xylazine is often mixed with opioids, naloxone can be helpful to lessen the effects of the opioid overdose. However, overdoses that involve xylazine could require additional medical attention.
Repeated exposure may result in dependence and withdrawal. Withdrawal symptoms such as agitation or severe anxiety may occur when the drug is decreased or discontinued. Such symptoms can undermine a patient’s effort to obtain appropriate treatment for concurrent Opioid Use Disorder (OUD).
Complications from using xylazine can be debilitating. The sedation caused by xylazine can lead a person to black out up to four hours. While unconscious the person can sometimes not be awakened. They may stay in the same position for hours if they fall or collapse. This can cut off blood supply to limbs and extremities. Xylazine sedation can also leave a person vulnerable to heat or cold exposure if outdoors. There is also a risk of choking or being unable to breathe if the airway is obstructed. Injecting xylazine can cause severe wounds that can sometimes take months to heal. Wounds can become necrotic, leading to surgery or amputation. Wounds can appear anywhere there is an opening in your skin, not just the injection site.
The effects of xylazine can be felt for up to four hours. Someone who has recently used the drug could test positive on a urine drug test for several days. However, most standard drug tests do not detect xylazine, additional analytical techniques are required.
According to FDA’s review of case reports from the FDA Adverse Event Reporting System, National Poison Data System, Toxicology Investigators Consortium, and published medical literature, acute and recurrent xylazine exposure may be associated with clinically significant harms such as delaying the diagnosis and management of polysubstance overdose; developing severe, necrotic skin ulcerations; and interfering with the successful treatment of opioid use disorder.
Health care professionals should consider potential xylazine exposure when patients presenting with an overdose do not respond to naloxone. In these situations, health care professionals should provide supportive measures and consider screening for xylazine using appropriate tests. Additionally, health care professionals who see patients with severe, necrotic skin ulcerations should consider repeated xylazine exposure as part of the differential diagnosis. Finally, health care professionals caring for patients with OUD should monitor patients for withdrawal symptoms not managed by traditional OUD treatments, as this may indicate xylazine withdrawal.
The FDA encourages health care professionals and patients to report adverse events in humans associated with possible illicit xylazine exposure to FDA’s MedWatch Adverse Event Reporting program. Complete and submit the report online at www.fda.gov/medwatch/report.htm; or download and complete the form, then submit it via fax at 1-800-FDA-0178. (3)
Sources: 1) What is xylazine? DEA warns of veterinary tranquilizer linked to overdose deaths: NPR. 2) A new drug is worsening the fentanyl crisis and complicating treatment: NPR. 3) FDA alerts health care professionals of risks to patients exposed to xylazine in illicit drugs | FDA. 4) What is Fentanyl Prescribed For? | Fentanyl Uses and Dosages (therecoveryvillage.com). 5) 2023.05.23_xylazine_factsheet.pdf (drugpolicy.org) 6) Xylazine one-pager draft (harmreduction.org)