Fentanyl with Posaconazole Interaction Details

Brand Names Associated with Fentanyl

Brand Names Associated with Posaconazole

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 31, 2023

Interaction Effect

An increased risk of fentaNYL-related toxicity

Interaction Summary

Use caution when coadministering fentaNYL (a CYP3A4 substrate) and a CYP3A4 inhibitor such as fluconazole as this may increase fentaNYL exposure and increase the risk of fentaNYL-related side effects possibly resulting in fatal respiratory depression. If concomitant use is required, reduce the fentaNYL dose, as appropriate, and monitor patients for adverse effects including sedation and respiratory depression.

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

The concomitant use of fentaNYL, a CYP3A4 substrate, and a CYP3A4 inhibitor such as fluconazole should be undertaken with caution as this may increase fentaNYL exposure and increase the risk of fentaNYL-related side effects, possibly resulting in fatal respiratory depression. If coadministration of fentaNYL and a CYP3A4 inhibitor is required, monitor patients for adverse effects including sedation and respiratory depression and reduce the fentaNYL dose as appropriate.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of fentaNYL

Literature Reports

A) One fatal case of possible fentaNYL-fluconazole interaction was reported. The author judged that the patient died from fentaNYL intoxication. Furthermore, in a randomized crossover study with 12 healthy volunteers, it was shown that fluconazole delayed the elimination of fentaNYL significantly. Elevated fentaNYL concentration may lead to respiratory depression .

B) Twelve healthy volunteers received either placebo or ritonavir orally 3 times daily for 3 days, with a dose of fentaNYL 5 mcg/kg IV being administered after the second dose of ritonavir on the second day. To prevent the sedative and respiratory depressant effects of fentaNYL, naloxone was given before and with the fentaNYL dose. One subject discontinued the study before the administration of fentaNYL. In the 11 remaining participants, ritonavir decreased the plasma clearance of fentaNYL by 67% (from 15.6 to 5.2 mL/min/kg). The elimination half-life of fentaNYL increased from 9.4 hours to 20.1 hours after ritonavir, and the area under the concentration-time curve (AUC) increased by 174% (from 6.6 to 18.1 ng/mL/hr) when compared to placebo. It is considered probable that ritonavir would similarly affect the elimination of transdermally administered fentaNYL .

C) Coadministration of fluconazole with a single IV dose of fentaNYL decreased the mean plasma clearance of fentaNYL by 16% in an open, randomized, crossover study. Twelve healthy volunteers received a single IV dose of fentaNYL 5 mcg/kg either alone (control phase) or 1 hour following receipt of the final dose of fluconazole on day 2 (400 mg orally once daily on day 1, followed by 200 mg orally once daily on day 2). To prevent the sedative and respiratory depressant effects of fentaNYL, naloxone was given before and with the fentaNYL dose. All 12 subjects completed the study. During the fluconazole phase, the mean plasma clearance was decreased by 16% (range, -34% to 53%; p less than 0.05) compared with the control phase. Also, while a nonsignificant increase in the fentaNYL AUC was observed (fluconazole phase, 7.7 +/- 2.3 nanograms (ng) x hr/mL vs control phase 6.1 +/- 1.1 ng x hr/mL), a notable decrease in the inactive metabolite, norfentaNYL, occurred (fluconazole phase, 0.8 +/- 0.7 ng x hr/mL vs control phase, 1.8 +/- 1.1 ng x hr/mL) and the ratio of the norfentaNYL AUC to the fentaNYL AUC was significantly lower in the fluconazole phase compared with the control phase (AUC ratio, 0.1 +/- 0.1 vs 0.3 +/- 0.2). The mean elimination half-life of fentaNYL did not differ between the phases. The change in fentaNYL clearance appeared to be due to the inhibition of CYP3A4-mediated N-dealkylation of fentaNYL to norfentanyl .

D) A 46-year-old man receiving transdermal fentaNYL died following concurrent treatment with fluconazole. The patient was experiencing oral pain caused by radiation therapy for tonsillar cancer was treated with fentaNYL 100 mcg/hr transdermal patch. Over the next 1.5 months, the fentaNYL dose was increased to 150 mcg/hr. Concomitant medications included morphine 10 mg orally once daily, diclofenac 50 mg orally 3 times daily, paracetamol 1000 mg orally 3 times daily, oxazepam 15 mg orally twice daily, zolpidem 5 mg orally nightly, nystatin (100,000 international units/mL) 4 times daily, metoclopramide 20 mg rectally 3 times daily, lidocaine oral spray, and lactulose. Two weeks after increasing the fentaNYL dose to 150 mcg/hr, the patient underwent a percutaneous gastrostomy because of worsening dysphagia. He developed an oral fungal infection 8 days later and was started on oral fluconazole 50 mg/day. Three days later, he died in his sleep. Forensic analysis revealed a toxic concentration of fentaNYL (0.017 mcg/g), high concentrations of fluconazole (2.4 mcg/g), lidocaine (1.6 mcg/g), and metoclopramide (0.15 mcg/g), along with a therapeutic concentration of zolpidem. The forensic analysis did not reveal any signs of ethanol or drugs of abuse. The only pathological findings noted from the autopsy were pulmonary congestion and brain edema. There was no sign of intentional overdosing, and the coroner concluded that respiratory depression and circulatory failure from fentaNYL intoxication was the cause of death .

E) Coadministration of voriconazole with a single IV dose of fentaNYL increased the mean AUC of fentaNYL by 1.4-fold and decreased the mean plasma clearance by 23% in an open, randomized, crossover study. Twelve healthy volunteers received a single IV dose of fentaNYL 5 mcg/kg either alone (control phase) or 1 hour following receipt of the final dose of voriconazole on day 2 (400 mg orally twice daily on day 1, followed by 200 mg orally twice daily on day 2). To prevent the sedative and respiratory depressant effects of fentaNYL, naloxone was given before and with the fentaNYL dose. All 12 subjects completed the study. During the voriconazole phase, the mean AUC (0 to infinity) of fentaNYL was increased by 1.4-fold (range, 0.81- to 2.04-fold) and the mean plasma clearance was decreased by 23% (range -22% to 48%) compared with the control phase. Notably, the mean fentaNYL plasma concentration at 12 hr during the voriconazole phase matched the level at 6 hr during the control phase. The mean elimination half-life of fentaNYL also did not differ between the phases. Nausea and vomiting were reported in 4 subjects during the voriconazole phase and in 2 subjects during the control phase. No further doses of naloxone were required and no other adverse events were reported .

Fentanyl Overview

• Fentanyl is used to treat breakthrough pain (sudden episodes of pain that occur despite round the clock treatment with pain medication) in cancer patients at least 18 years of age (or at least 16 years of age if using Actiq brand lozenges) who are taking regularly scheduled doses of another narcotic (opiate) pain medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic (opiate) analgesics. It works by changing the way the brain and nervous system respond to pain.

Posaconazole Overview

• Posaconazole is used to prevent serious fungal infections that can spread throughout the body in adults and children 2 years of age and older with a weakened ability to fight infection. Posaconazole delayed-release tablets are used to treat invasive aspergillosis (a serious fungal infection that begins in the lungs and spreads through the bloodstream to other organs) in adults and teenagers 13 years of age and older. Posaconazole oral suspension is also used to treat yeast infections of the mouth and throat including yeast infections in adults and teenagers 13 years of age and older that could not be treated successfully with other medications. Posaconazole is in a class of medications called azole antifungals. It works by slowing the growth of fungi that cause infection.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.