Fentanyl

Chronic Pain Management

Fentanyl skin patches are used to manage severe pain that is expected to last for a long time. They are prescribed for patients who require continuous, around-the-clock pain relief that cannot be managed by other types of medication.

Breakthrough Cancer Pain

Certain forms of fentanyl, such as lozenges, films, or nasal sprays, are used specifically to treat breakthrough pain in people with cancer. Breakthrough pain refers to sudden flares of intense pain that occur even though the person is already taking regular doses of long-acting pain medicine.

Opioid Tolerance

Fentanyl is only for use in patients who are considered opioid-tolerant. This means the patient has been taking regular, daily doses of another opioid medication for a period of time and their body has become used to the effects. It is not used for:

• Short-term pain from an injury or surgery.
• Occasional or mild pain.
• Patients who are not already taking daily opioid medication.

Mechanism of Action

Fentanyl belongs to a class of drugs known as opioid analgesics. It works by binding to specific proteins called opioid receptors, which are found in the brain, spinal cord, and other parts of the nervous system.

When these receptors are activated by fentanyl, the medication helps to:

• Block pain signals sent from the nerves to the brain.
• Change the way the brain interprets and reacts to pain.

Because fentanyl is a very strong synthetic opioid, it is significantly more potent than many other pain medications. It is designed to provide relief for severe pain, such as pain following surgery or breakthrough cancer pain in patients who are already used to taking opioid medications around the clock.

Common Side Effects

Many people using fentanyl experience mild to moderate side effects. These may include:

• Nausea and vomiting
• Constipation
• Drowsiness, dizziness, or lightheadedness
• Headache
• Dry mouth
• Stomach pain or loss of appetite
• Weakness or fatigue
• Increased sweating
• Redness, itching, or irritation at the site of a patch or application

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Contact a healthcare provider or seek emergency care if you experience:

• Slowed, shallow, or difficult breathing
• Extreme sleepiness or inability to wake up
• Confusion or disorientation
• Fainting or feeling faint
• Chest pain
• Fast, slow, or pounding heartbeat
• Seizures
• Severe muscle stiffness
• Hallucinations or extreme agitation
• Symptoms of serotonin syndrome, such as shivering, muscle twitching, loss of coordination, fever, or severe diarrhea
• Signs of an allergic reaction, including rash, hives, or swelling of the face, tongue, or throat

Fentanyl use can lead to physical dependence. If the medication is stopped suddenly after regular use, withdrawal symptoms may occur. These can include restlessness, anxiety, irritability, sleep problems, muscle aches, sweating, and chills.

Addiction, Abuse, and Misuse

Fentanyl is a potent opioid with a high risk for addiction, abuse, and misuse, which can lead to overdose and death. Healthcare providers monitor patients for signs of these risks throughout treatment.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal breathing problems may occur. This risk is highest when first starting the medication or when the dose is increased. Patients with lung diseases or those who are elderly or debilitated may be at higher risk.

Accidental Exposure and Pediatric Safety

Accidental exposure to fentanyl, particularly in children, can result in a fatal overdose. This includes accidental contact with a skin patch or ingestion of other forms. To prevent accidental contact by others, used patches are disposed of by folding the adhesive sides together and flushing them down the toilet.

Neonatal Opioid Withdrawal Syndrome

Long-term use of fentanyl during pregnancy can lead to withdrawal symptoms in the newborn. This condition can be life-threatening if not recognized and treated by medical professionals.

Interactions with Other Substances

Using fentanyl with benzodiazepines, alcohol, or other central nervous system depressants may result in profound sedation, respiratory depression, coma, and death. Additionally, certain medications that affect liver enzymes can increase the amount of fentanyl in the blood, leading to dangerous levels of the drug.

Restricted Access (TIRF REMS)

Because of the risks of misuse and overdose, certain fast-acting fentanyl products are only available through a restricted distribution program called the TIRF REMS Access program.

Other Medical Considerations

• Serotonin Syndrome: A serious reaction can occur when fentanyl is taken with certain antidepressants or other drugs that affect serotonin levels.
• Adrenal Insufficiency: Long-term opioid use may cause the adrenal glands to stop producing enough cortisol.
• Gastrointestinal Risks: Fentanyl is not recommended for patients with known or suspected blockages in the stomach or intestines.

Pregnancy

Using fentanyl during pregnancy, especially for a prolonged period, may lead to physical dependence in the newborn. This can result in neonatal opioid withdrawal syndrome, a condition that requires medical management. Symptoms in the infant may include:

• Irritability and excessive crying
• Tremors or shaking
• Abnormal sleep patterns
• Vomiting or diarrhea
• Failure to gain weight

If you are pregnant or planning to become pregnant, it is important to discuss the risks and benefits of fentanyl with your healthcare provider. Abruptly stopping opioid treatment during pregnancy can also carry risks, so any changes to medication should be supervised by a medical professional.

Breastfeeding

Fentanyl passes into breast milk and can cause serious side effects in a nursing infant. These may include extreme sleepiness, sedation, or life-threatening breathing problems. Healthcare providers generally advise monitoring the baby closely for these symptoms or discussing alternative treatments if you plan to breastfeed.

Dosage Forms

Fentanyl is available in several formulations designed for specific types of pain management. These include long-acting options for chronic pain and rapid-acting options for breakthrough pain.

• Transdermal Patches: These are applied to the skin and provide continuous delivery of the medication over a 72-hour period.
• Lozenges: Often provided on a handle, these are dissolved in the mouth to be absorbed through the oral mucosa.
• Buccal and Sublingual Tablets: These tablets are placed between the cheek and gum or under the tongue to dissolve.
• Nasal and Sublingual Sprays: These are sprayed into the nose or under the tongue for rapid absorption.
• Injectable Solutions: Fentanyl is available as a liquid for intravenous or intramuscular injection, usually administered by a healthcare professional in a clinical setting.

Strengths

Fentanyl is a highly potent medication measured in micrograms. The available strengths depend on the specific form of the drug. Patches are categorized by the amount of medication they deliver per hour, while transmucosal forms (like tablets and sprays) are categorized by the total microgram dose per unit. Dosage is determined by a healthcare provider based on the patient's specific needs and previous history with opioid medications.

FDA Approval and Controlled Status

Fentanyl is approved by the U.S. Food and Drug Administration (FDA) as a potent opioid analgesic. Due to its high potential for abuse, addiction, and misuse, it is classified as a Schedule II controlled substance under the Controlled Substances Act.

Approved Indications

The FDA has approved various formulations of fentanyl for specific uses in patients who are already opioid-tolerant:

• Transdermal Patches: Approved for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment when other treatments are inadequate.
• Transmucosal Immediate-Release Fentanyl (TIRF): These formulations, including lozenges, tablets, and sprays, are approved specifically for the management of breakthrough cancer pain.

Boxed Warnings and Safety Programs

Fentanyl products carry a Boxed Warning, the FDA’s most serious warning, regarding the risks of addiction, abuse, and misuse, which can lead to overdose and death. There is also a significant risk of life-threatening respiratory depression, even at recommended doses.

To mitigate these risks, the FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for certain products. The TIRF REMS program is designed to ensure that these medicines are only prescribed to and dispensed for opioid-tolerant patients by certified healthcare providers and pharmacies.

Safety Communications

The FDA has issued safety communications regarding the risk of accidental exposure, particularly in children. Fentanyl patches can be fatal to children if they accidentally touch, sit on, or swallow a patch. The FDA emphasizes the importance of proper storage and disposal, such as folding used patches with the adhesive sides together and flushing them down the toilet immediately to prevent accidental contact.

Risk of Addiction and Misuse

Fentanyl is classified as a Schedule II controlled substance because it has a high potential for abuse. Even when used exactly as prescribed by a healthcare provider, there is a risk of developing an opioid use disorder (addiction). This risk is significantly higher for individuals with a personal or family history of substance abuse or mental health conditions.

Tolerance and Physical Dependence

With regular use, the body may develop tolerance, meaning higher doses are needed to achieve the same pain-relieving effect. Long-term use also leads to physical dependence. If the medication is stopped suddenly, it can cause severe withdrawal symptoms, including:

• Restlessness and anxiety
• Muscle and bone pain
• Sleep problems
• Diarrhea and vomiting
• Cold flashes with goosebumps

Safe Use and Prevention

To reduce the risk of addiction, it is critical to take fentanyl exactly as directed. Sharing this medication with others is illegal and dangerous. Because of the high risks associated with certain forms of fentanyl, such as transmucosal products, the FDA requires a restricted distribution program called the Transmucosal Immediate-Release Fentanyl (TIRF) Risk Evaluation and Mitigation Strategy (REMS). This program is designed to ensure the medication is used safely and only by patients who are already opioid-tolerant.