Fentanyl (Duragesic) Warnings, Risks, and Complications

Opioid Overdose : The fentanyl transdermal system contains a large amount of medicine to be delivered over an extended period of time. It therefore carries a greater risk of serious harm, including overdose and death. Risk factors for opioid overdoses include concomitant use of other CNS depressant drugs, a history of opioid use disorder, or prior drug overdoses. Use fentanyl patches exactly as prescribed. Talk to your health care provider about having the rescue medication naloxone available for emergency treatment of an opioid overdose.

Addiction, Abuse, and Misuse: Fentanyl is an opioid drug and a Schedule II controlled substance due to its high potential for misuse, abuse, physical dependence, and addiction. Addiction and physical dependence on fentanyl can occur even when you use it at the recommended doses. The risk of addiction is higher if the drug is misused or abused (taking higher doses or more frequent doses than prescribed, using the fentanyl patches in ways other than prescribed, or using someone else’s fentanyl patches). Additional risk factors include a personal or family history of substance abuse (including prescription drugs, street drugs, or alcohol abuse or addiction) and mental illnesses such as depression and anxiety. 

Your doctor will carefully assess the risk of addiction before prescribing fentanyl to you and reassess you from time to time for signs of misuse, abuse, physical dependence, and addiction. They will prescribe the small quantities at a time, and you will have to meet certain criteria to obtain more patches. Make sure you store your fentanyl patches safely out of reach of others. Ask your healthcare provider to explain the proper disposal of any unused patches. 

Life-Threatening Respiratory Depression: Serious adverse effects such as life-threatening or fatal respiratory depression can occur with the use of opioids, even at the recommended doses. Respiratory depression can occur at any time during treatment with fentanyl, but the risk is highest with the first dose or after a dose escalation. Without timely treatment, respiratory depression (slowed or stopped breathing) can lead to respiratory arrest and death. 

Opioids can also increase the risk of sleep-related breathing disorders like central sleep apnea. You may need to decrease the dose of your opioid medication if you develop symptoms of sleep apnea.

Healthcare professionals only prescribe fentanyl patches to opioid-tolerant patients who have received other opioids previously. Follow your doctor’s dosing instructions carefully. Make sure you store the fentanyl patches safely out of reach. Accidental exposure, especially in children, can result in death due to a fentanyl overdose. Make sure you know how to recognize the signs of respiratory depression. Call 911 or seek emergency medical help right away if you develop slowed or shallow breathing while using fentanyl patches. 

The risk of life-threatening respiratory depression is higher in people with chronic lung diseases, elderly patients, and those who are cachectic or debilitated (in poor health). Your doctor will not prescribe fentanyl patches if you have severe lung disease.

Talk to your doctor about having access to naloxone for emergency treatment of an opioid overdose. Your caregivers should know how to administer naloxone in case of an opioid overdose and to call 911 or get emergency medical help administering naloxone.

Accidental Exposure: There is a considerable amount of residual fentanyl in fentanyl transdermal patches after they have been used. This residual medicine can cause death and other serious adverse effects in children and adults who may be accidentally exposed to the used patches. The risk of respiratory depression and death is particularly high in children and adolescents after accidental or deliberate application or ingestion of a patch. Never place fentanyl patches in your mouth, chew them, or swallow them - this can put you at risk of choking and overdose. Make sure you dispose of fentanyl patches properly to prevent accidental exposures.

Risks of Concomitant Use of CNS Depressants: Concomitant use of fentanyl with certain drugs such as other CNS depressants can lead to profound sedation, respiratory depression, coma, and death. Examples of CNS depressants include alcohol, anxiolytics, benzodiazepines, non-benzodiazepine sedatives/hypnotics, tranquilizers, muscle relaxants, antipsychotics, general anesthetics, and other opioids. Your doctor will avoid prescribing these drugs together unless absolutely necessary. If you need to take another CNS depressant along with an opioid analgesic such as fentanyl, your provider will prescribe the lowest effective dosages and for the minimum treatment duration. They may also prescribe naloxone for emergency use in case of an opioid overdose. Do not drive or operate heavy machinery until you know how fentanyl and other CNS depressants affect you. 

Neonatal Opioid Withdrawal Syndrome: The use of fentanyl patches for an extended time during pregnancy can result in withdrawal symptoms in the baby after birth. This is called neonatal opioid withdrawal syndrome and can be life-threatening if it is not recognized and treated in time. If you use fentanyl during pregnancy, observe your newborn carefully for signs of neonatal opioid withdrawal syndrome such as fussiness, excessive high-pitched crying, poor feeding, tight muscles, and seizures. 

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS): The U.S. Food and Drug Administration (FDA) has a Risk Evaluation and Mitigation Strategy (REMS) program for opioid analgesics to prevent their misuse, abuse, and addiction. REMS requires drug companies that manufacture these drugs to make education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete REMS education programs, discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or caregivers each time these medicines are prescribed, emphasize the importance of reading the Medication Guide, and use other tools to improve opioid safety, such as patient-prescriber agreements. Follow your doctor’s recommendations and make sure you meet the requirements of REMS for your safety.

Drug Interactions: Using fentanyl transdermal patches with CYP3A4 inhibitors, such as azole-antifungals (for example, ketoconazole), macrolide antibiotics (for example, erythromycin), and protease inhibitors (for example, ritonavir) or CYP3A4 inducers, such as antitubercular drugs (for example, rifampin) and antiseizure drugs (for example, carbamazepine and phenytoin) or discontinuing these drugs while on fentanyl patches can affect the plasma concentrations of fentanyl. Increased fentanyl concentrations can cause serious adverse effects, and decreased fentanyl concentrations can cause withdrawal symptoms. If you are taking CYP3A4 inhibitors or inducers, your doctor will evaluate you at frequent intervals and may change your fentanyl dose until stable drug levels are achieved. 

Risk of Increased Drug Absorption with Heat: The application of heat over a fentanyl transdermal patch can lead to increased fentanyl absorption, which can lead to overdose and death. Avoid exposing your fentanyl patch to a direct heat source such as heat lamps, heating pads, electric blankets, or hot baths. 

Serum fentanyl concentrations could also, at least theoretically, increase if your body temperature is above 40°C (104°F). Tell your doctor if you develop a fever. Avoid strenuous exertion that could potentially increase your core body temperature. Seek emergency medical care if you develop extreme sleepiness or slowed breathing. 

Opioid-Induced Hyperalgesia and Allodynia: Sometimes, using opioid pain medications can cause a paradoxical increase in pain or increased pain sensitivity. This can occur with both short- and long-term use of fentanyl patches. Symptoms may include increased pain with an increase in the dose of fentanyl, decreased pain with a decrease in the dose of fentanyl, or pain from stimuli that are typically not painful. Your doctor will rule out other conditions, such as disease progression, opioid tolerance, opioid withdrawal, and addiction. If you are diagnosed with opioid-induced hyperalgesia, your doctor will carefully decrease the dose of fentanyl patches and give you a different opioid.

Serotonin Syndrome: Serotonin syndrome is a potentially life-threatening condition that can occur if you use fentanyl patches with other serotonergic drugs (drugs that increase serotonin levels). Examples of serotonergic drugs include antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs); migraine medications called triptans; drugs used to manage chemotherapy-associated nausea and vomiting (5-HT3 receptor antagonists); drugs that affect the serotonergic system, for example, mirtazapine, trazodone, tramadol); certain muscle relaxants such as cyclobenzaprine and metaxalone; drugs that impair serotonin metabolism, for example, MAO inhibitors. 

Serotonin syndrome can occur even when you take these medications at the recommended doses. Symptoms may include changes in mental status (confusion, agitation, hallucinations), autonomic instability (fast heartbeat, changes in blood pressure, elevated body temperature), neuromuscular changes (increased reflexes, incoordination, muscle rigidity), and/or gastrointestinal symptoms (nausea, vomiting, diarrhea). These symptoms typically occur within a few hours to days of using serotonergic drugs, but may occur later. You will need to discontinue fentanyl transdermal patches immediately if you have suspected serotonin syndrome.

Adrenal Insufficiency: There are reports of adrenal insufficiency (reduced adrenal gland function) with opioid use, especially after more than a month of treatment with these drugs. Symptoms of adrenal insufficiency are usually non-specific and may include nausea, vomiting, loss of appetite, weakness, tiredness, dizziness, and low blood pressure. If your doctor suspects adrenal insufficiency, they will perform diagnostic testing, and if a diagnosis is confirmed, you will need to take replacement corticosteroids and reduce your fentanyl dose to allow your adrenal function to recover. You may be able to take other opioids for pain relief. We do not know if one type of opioid drug is more likely to cause adrenal insufficiency than others.

Severe Hypotension: Using fentanyl patches can lead to severe hypotension (dangerously low blood pressure), including orthostatic hypotension and syncope (fainting when going from a sitting or lying position to standing). The risk is higher in people who have low blood volume or are taking other CNS depressant drugs which can have additive effects. Your doctor will check your blood pressure regularly. Tell your doctor if you develop lightheadedness or fainting.

Risks in Patients with Head Injuries : Fentanyl patches can lower respiratory drive in patients with increased intracranial pressure and brain tumors. They can also obscure the clinical course in people with head injuries. Your doctor will avoid using fentanyl if you have impaired consciousness, increased intracranial pressure, head injury, or brain tumor. 

Heart Disease: Fentanyl transdermal patches may cause bradycardia (slowed heart rate). Your doctor will evaluate your heart rate regularly, especially when first starting treatment. 

Hepatic Impairment: Fentanyl is metabolized by the liver. When administered as transdermal patches, the drug has a long half-life (it stays in the body longer). Therefore, in people with hepatic impairment (reduced liver function), the systemic exposure to fentanyl is increased. Your doctor will not prescribe fentanyl patches if you have severe liver disease. If you have mild to moderate liver disease, they may start treatment with a lower dose of fentanyl and evaluate you regularly for signs of sedation and respiratory depression. 

Renal Impairment: People with renal impairment (reduced kidney function) and high blood urea nitrogen have reduced fentanyl elimination from the body. When administered in the form of transdermal patches, the drug has a long half-life (it stays in the body longer). Therefore, your doctor will avoid the use of fentanyl patches if you have severe renal impairment. If you have mild to moderate renal impairment, your provider may start you on a lower dose and monitor you carefully during therapy.

Risks in Patients with Gastrointestinal Conditions: Fentanyl can cause spasms of the sphincter of Oddi (a muscle in the bile and pancreatic ducts). It can also cause an increase in serum amylase levels. Therefore, fentanyl transdermal patches should not be used by people with known or suspected obstructions in the gastrointestinal tract, including paralytic ileus, or biliary tract disease, including acute pancreatitis.

Risk in Patients with Seizure Disorders: Fentanyl can increase the frequency of seizures in people with seizure disorders and increase the risk of seizures in certain situations. If you have a seizure disorder, your doctor will evaluate you regularly for seizure control.

Withdrawal Symptoms: Long-term use of fentanyl can lead to physical dependence. Stopping the use of fentanyl patches suddenly after using them for a long time can lead to withdrawal symptoms. Your doctor will tell you how to gradually lower the dose. They will also avoid prescribing a mixed opioid agonist/antagonist (for example, pentazocine, butorphanol, or nalbuphine) or a partial opioid agonist (for example, buprenorphine) as these drugs can reduce the pain-relieving effects of fentanyl patches or cause withdrawal symptoms.

Risks of Driving and Operating Machinery: Using fentanyl transdermal patches can impair your ability to focus and pay attention, putting you at risk while driving or operating machinery. Do not perform any potentially hazardous activities until you know how this medication affects you.