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Drug Interactions between belzutifan and Fentanyl Transdermal System

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

fentaNYL belzutifan

Applies to: Fentanyl Transdermal System (fentanyl) and belzutifan

MONITOR CLOSELY: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of opioids that are primarily metabolised by the isoenzyme such as butorphanol, fentanyl, hydrocodone, and oxycodone. Reduced efficacy or withdrawal symptoms may occur in patients maintained on their narcotic pain regimen following the addition of a CYP450 3A4 inducer. Conversely, discontinuation of the inducer may increase opioid plasma concentrations and potentiate the risk of overdose and fatal respiratory depression. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Pharmacologic response to the opioid should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the opioid dosage adjusted as necessary. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath.

References

  1. (2001) "Product Information. Mycobutin (rifabutin)." Pharmacia and Upjohn
  2. (2001) "Product Information. Rifadin (rifampin)." Hoechst Marion Roussel
  3. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  4. (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. (2006) "Product Information. Ionsys (fentanyl)." Ortho McNeil Pharmaceutical
  7. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  8. Cerner Multum, Inc. "Australian Product Information."
  9. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc
  10. (2017) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
View all 10 references

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Drug and food interactions

Major

fentaNYL food

Applies to: Fentanyl Transdermal System (fentanyl)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including fentanyl. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of grapefruit juice during treatment with oral transmucosal formulations of fentanyl may result in increased plasma concentrations of fentanyl, which is primarily metabolized by CYP450 3A4 isoenzyme in the liver and intestine. Certain compounds present in grapefruit are known to inhibit CYP450 3A4 and may increase the bioavailability of swallowed fentanyl (reportedly up to 75% of a dose) and/or decrease its systemic clearance. The clinical significance is unknown. In 12 healthy volunteers, consumption of 250 mL regular-strength grapefruit juice the night before and 100 mL double-strength grapefruit juice one hour before administration of oral transmucosal fentanyl citrate (600 or 800 mcg lozenge) did not significantly affect fentanyl pharmacokinetics, overall extent of fentanyl-induced miosis (miosis AUC), or subjective self-assessment of various clinical effects compared to control. However, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with fentanyl. Any history of alcohol or illicit drug use should be considered when prescribing fentanyl, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with fentanyl should preferably avoid the consumption of grapefruit and grapefruit juice. In addition, patients receiving transdermal formulations of fentanyl should be cautioned that drug interactions and drug effects may be observed for a prolonged period beyond removal of the patch, as significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the patch is removed.

References

  1. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  2. (2001) "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical
  3. Kharasch ED, Whittington D, Hoffer C (2004) "Influence of Hepatic and Intestinal Cytochrome P4503A Activity on the Acute Disposition and Effects of Oral Transmucosal Fentanyl Citrate." Anesthesiology, 101, p. 729-737
  4. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M (1996) "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg, 82, p. 167-72
  5. Labroo RB, Paine MF, Thummel KE, Kharasch ED (1997) "Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implicaitons for interindividual variability in disposition, efficacy, and drug interactions." Drug Metab Dispos, 25, p. 1072-80
View all 5 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.