FENTANYL

1. Drug Name

• Generic Name: Fentanyl

• Brand Names: Duragesic, Sublimaze, Actiq, Fentora, Lazanda, Onsolis, Abstral.

2. Drug Classification

• Class: Opioid analgesic

• Subclass: Synthetic opioid

3. Mechanism of Action

• Primary Action: Fentanyl is a potent μ-opioid receptor agonist in the central nervous system (CNS), providing analgesia by binding to opioid receptors and inhibiting nociceptive transmission.

• Analgesic Effects: Fentanyl blocks pain signals by reducing neurotransmitter release in presynaptic nerve terminals, hyperpolarizing postsynaptic neurons, and inhibiting ascending pain pathways.

• Additional Effects: Besides analgesia, fentanyl causes sedation, euphoria, and respiratory depression. Its rapid onset and high potency make it effective for intense, acute pain but also contribute to its high abuse and addiction potential.

4. Pharmacokinetics

• Absorption: High bioavailability varies by route (IV: 100%; transdermal: ~92%); onset is rapid with IV and transmucosal routes.

• Distribution: Volume of distribution (Vd) is around 4 L/kg, with approximately 80-85% plasma protein binding.

• Metabolism: Extensively metabolized in the liver, primarily via CYP3A4, to inactive metabolites.

• Excretion: Half-life (t½) of 3-12 hours, primarily excreted in urine as inactive metabolites.

• Special Considerations: Age, liver dysfunction, and route affect pharmacokinetics significantly; transdermal patches are suitable for chronic pain management, but dosing must be carefully titrated.

5. Indications

• Primary Indications:

  • Management of severe chronic pain in patients who require continuous, long-term opioid analgesia and are opioid-tolerant.

  • Acute pain management during surgical procedures (IV form).

• Off-label Uses:

  • Control of severe refractory pain in cancer patients.

  • Palliative care settings for advanced pain management.

• Beneficial Populations: Patients with chronic, opioid-resistant pain, and those in surgical or intensive care units needing quick analgesia.

6. Dosage and Administration

• Adult Dosing:

  • IV (Acute Pain): Initial dose 50-100 mcg every 1-2 hours as needed.

  • Transdermal Patch (Chronic Pain): 12-100 mcg/hour every 72 hours; dosing individualized based on opioid tolerance.

  • Buccal/Transmucosal (Breakthrough Pain): Start at 100 mcg; titrate according to patient response.

• Pediatric Dosing: IV dosing is weight-based; transdermal use not typically recommended.

• Routes: IV, transdermal, buccal, sublingual, nasal spray, intramuscular.

• Renal/Hepatic Adjustments: Use caution in hepatic impairment; renal impairment may necessitate dose adjustments due to prolonged effects.

7. Contraindications

• Hypersensitivity to fentanyl or other opioids.

• Use in non-opioid-tolerant patients (especially transdermal and transmucosal forms).

• Severe respiratory depression, acute or severe bronchial asthma in unmonitored settings.

• Postoperative pain in patients without adequate respiratory monitoring (particularly with transdermal patches).

8. Warnings and Precautions

• Black Box Warnings: Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental exposure, especially in children; risks of concomitant CNS depressants; neonatal opioid withdrawal syndrome with prolonged use during pregnancy.

• Pregnancy and Lactation: Potential for neonatal withdrawal syndrome if used long-term in pregnancy; fentanyl passes into breast milk, so caution is advised.

• Monitoring Parameters: Respiratory rate, sedation level, blood pressure, and signs of dependence/misuse.

• Special Considerations: Extreme caution in elderly patients, patients with compromised pulmonary function, and in combination with other CNS depressants due to risk of additive respiratory depression.

9. Adverse Effects

• Common Adverse Effects (≥10%): Nausea, vomiting, constipation, sedation, dizziness, respiratory depression, and headache.

• Less Common but Clinically Significant: Hypotension, urinary retention, rash, and sweating.

• Serious Adverse Reactions: Severe respiratory depression, apnea, bradycardia, circulatory depression, anaphylactic reactions, tolerance, dependence, and risk of overdose with improper use.

10. Drug Interactions

• Major Drug Interactions:

  • CNS Depressants (e.g., benzodiazepines, alcohol): Increased risk of profound sedation, respiratory depression, coma, and death.

  • CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase fentanyl levels, leading to enhanced effects or toxicity.

  • MAO Inhibitors: Risk of serotonin syndrome when used with serotonergic drugs.

• Food-Drug Interactions: Transmucosal products may have altered absorption if taken with grapefruit juice or other CYP3A4 inhibitors.

• Lab Test Interference: Fentanyl may interfere with some opioid drug screens.

11. Clinical Pharmacology

• Pharmacodynamic Profile: As a μ-opioid receptor agonist, fentanyl’s pharmacologic effects involve significant inhibition of pain signal transduction in the CNS. The drug exhibits a more favorable hemodynamic profile than morphine due to lower histamine release, reducing risks of hypotension.

• Additional Effects: Causes substantial euphoria, contributing to its abuse potential; has antitussive effects.

12. Special Populations

• Pregnancy: Category C; use only if clearly needed, as prolonged use increases the risk of neonatal withdrawal syndrome.

• Lactation: Excreted in breast milk; use with caution in nursing mothers.

• Geriatric Use: Start with lower doses due to higher sensitivity to effects and increased risk of respiratory depression.

• Renal/Hepatic Impairment: Use cautiously with dose adjustments, particularly in liver impairment, due to prolonged effects.

13. Therapeutic Uses

• First-Line Use: Indicated as a potent analgesic for severe, intractable pain in opioid-tolerant patients, particularly in cancer pain management.

• Combinational Therapy: Often used alongside other analgesics or sedatives in ICU or surgical settings.

• Clinical Trials and Efficacy: Fentanyl’s rapid onset and potency make it a gold standard for acute pain in operative and palliative care, with extensive evidence supporting its safety and efficacy in controlled settings.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Routine liver function and renal tests in long-term therapy, serum electrolytes.

• Patient Symptom Checklists: Regular assessment for respiratory depression, constipation, sedation, and signs of opioid misuse.

• Therapeutic and Toxic Levels: Monitor for efficacy and signs of overdose, particularly in compromised respiratory function or altered mental status.

15. Overdose Management

• Symptoms of Overdose: Respiratory depression, hypoventilation, miosis, somnolence, hypotension, and bradycardia.

• Treatment Protocols:

  • Naloxone is the antidote for fentanyl overdose, though repeated dosing may be necessary due to fentanyl’s duration.

  • Supportive Measures: Immediate airway management and ventilation support as needed.

• Monitoring in Overdose: Continuous monitoring of respiratory and cardiovascular function.

16. Patient Counseling Information

• Key Counseling Points:

  • Only use fentanyl as prescribed; never use for mild or intermittent pain.

  • Avoid combining with other sedatives, especially alcohol and benzodiazepines.

  • Do not expose transdermal patches to heat sources as this may cause rapid release of fentanyl.

  • Recognize signs of overdose, including trouble breathing, extreme drowsiness, and confusion.

• Signs Requiring Immediate Attention: Difficulty breathing, severe sedation, confusion, or symptoms of an allergic reaction.