Fentanyl

• Severe Chronic Pain
• Cancer Pain
• Breakthrough Pain
• Anesthesia

Fentanyl is a potent synthetic opioid analgesic used for the management of severe pain, including cancer pain and breakthrough pain in opioid-tolerant patients, as well as for anesthesia. This medication is approximately 100 times more potent than morphine and requires careful dosing and patient selection due to significant risks including fatal respiratory depression.

Mechanism of Action

Fentanyl is a full agonist at mu-opioid receptors, with some activity at kappa and delta receptors. Binding to mu-opioid receptors in the central nervous system produces analgesia, euphoria, respiratory depression, and physical dependence. The drug's high lipophilicity allows rapid penetration of the blood-brain barrier, producing faster onset of action compared to less lipophilic opioids. Fentanyl also binds to opioid receptors in the spinal cord and peripheral tissues, contributing to its analgesic effects. The rapid onset and short duration of IV fentanyl make it ideal for procedural analgesia and anesthesia.

Available Formulations

Fentanyl is available in numerous formulations for different routes and indications: transdermal patches (12, 25, 50, 75, 100 mcg/hour), transmucosal lozenge (oral transmucosal fentanyl citrate), buccal tablet, buccal film, nasal spray, sublingual tablet, sublingual spray, and injection. Each formulation has specific approved indications and is not interchangeable. Transdermal patches are for chronic pain; transmucosal formulations are specifically for breakthrough cancer pain in opioid-tolerant patients.

Medical Uses

Fentanyl injection is used for perioperative analgesia and as a supplement to anesthesia. Transdermal fentanyl is indicated for management of pain in opioid-tolerant patients severe enough to require daily, around-the-clock opioid treatment. Transmucosal fentanyl products (TIRF - Transmucosal Immediate-Release Fentanyl) are indicated only for breakthrough cancer pain in opioid-tolerant cancer patients already receiving and tolerant to around-the-clock opioid therapy.

Dosing Guidelines

Dosing varies significantly by formulation and indication. For transdermal patches, conversion from prior opioid therapy is required; patches are applied every 72 hours. For breakthrough pain products, dosing starts at the lowest available dose regardless of maintenance opioid dose, with careful titration. Injectable fentanyl doses for analgesia range from 25-100 mcg IV; anesthetic doses are much higher. Only patients receiving at least 60 mg oral morphine equivalents daily for at least 1 week are considered opioid-tolerant for fentanyl initiation.

Important Safety Information

Fentanyl carries a boxed warning for life-threatening respiratory depression, particularly during initiation and dose increases; accidental exposure can cause fatal overdose (especially in children); serious risks from concomitant use with benzodiazepines or CNS depressants; neonatal opioid withdrawal syndrome; and addiction, abuse, and misuse potential. TIRF products are available only through a restricted program (TIRF REMS). Transdermal patches can cause fatal overdose if heat is applied or in febrile patients. Naloxone should be available for emergency reversal.

Drug Interactions

Concomitant use with benzodiazepines, other CNS depressants, or alcohol can cause profound sedation, respiratory depression, coma, and death. CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin, grapefruit juice) increase fentanyl levels and may cause fatal respiratory depression. CYP3A4 inducers may decrease efficacy. Serotonergic drugs may cause serotonin syndrome. MAO inhibitors are contraindicated (or require washout period).

Special Populations

Fentanyl use during pregnancy can cause neonatal opioid withdrawal syndrome; chronic use should be avoided if possible. It is excreted in breast milk; breastfeeding is not recommended. Safety and efficacy of transdermal fentanyl have not been established in pediatric patients under 2 years; TIRF products are not for pediatric use. Elderly patients may be more sensitive and should start at lower doses. Dose reduction is needed in hepatic impairment. Renal impairment may increase sensitivity; use with caution.