Immunodeficiency Clinic > Drug Interaction Guide
You Selected:
Lopinavir/Ritonavir & Fentanyl (Duragesic®) [class:red]
Summary/Recommendation:
Potential ↑ fentanyl concentrations. Due to the risk of clinically significant toxicity including respiratory depression, coadministration is not recommended.
Data:
Potential ↑ fentanyl concentration via CYP3A4 inhibition by ritonavir.
Pharmacokinetic study with ritonavir: In a healthy volunteer study, a 67% reduction in clearance and 174% increase in AUC of fentanyl was observed when IV fentanyl was coadministered with ritonavir 900 mg/day. Monitor for respiratory and CNS depression.1002
Significant interactions between transdermal fentanyl and CYP3A4 inhibitors including itraconazole, fluconazole, clarithromycin and lopinavir/ritonavir have been reported, with consequences including opioid toxicity, respiratory depression and/or death. These cases are described in more detail below.
Clarithromycin: an 81 year old male with dementia, COPD, cervical spondylosis and spinal stenosis received H. pylori treatment with clarithromycin and metronidazole while on fentanyl 200 ug/hour. Thirty-six hours after the antibiotics were started, he was unresponsive to verbal and tactile stimuli and was treated with naloxone. He was subsequently stabilized on fentanyl 100 ug/hour.2799
Fluconazole: a 46 year old man with tonsillar cancer was on fentanyl 150 ug/hour for pain control. Three weeks later, fluconazole 50 mg daily was started for oral candidiasis. The patient died 3 days later; toxic fentanyl concentrations (approximately 6-fold greater than the upper therapeutic range) were noted.2788
Itraconazole: a 67 year old male with head and neck cancer was on fentanyl 50 ug/hour. He started treatment with itraconazole 200 mg BID for oropharyngeal candidiasis. Signs and symptoms of opioid toxicity were noted the next day, and he was eventually stablized on fentanyl 25 ug/hour.2797
Lopinavir/ritonavir: a 46 year old female on fentanyl 100 ug/hour received HIV post-exposure prophylaxis with lopinavir/ritonavir and zidovudine/lamivudine. Four days later she was very drowsy and needed frequent wakening. She was found unresponsive later that night.2800
The Norvir (ritonavir) monograph states that careful monitoring of therapeutic and adverse effects (including respiratory depression) is recommended when ritonavir is co-administered with fentanyl, including extended release, transdermal or transmucosal preparations.899
The Duragesic MAT (fentanyl) monograph states that concomitant use of transdermal fentanyl and CYP3A4 inhibitors is not recommended unless the patient is monitored closely for signs of respiratory depression. Monitoring should be done for an extended period of time, with fentanyl dose adjustments as required.2801
Due to the risk of clinically significant outcomes (including respiratory depression), coadministration of fentanyl with CYP3A4 inhibitors including cobicistat or ritonavir is not recommended.
