Monitor for signs/symptoms of opiate toxicity.
Potential for increased morphine and M6G concentrations via P-glycoprotein inhibition. Clinical significance unknown.
Coadministration of itraconazole 200 mg daily with oral morphine resulted in 22-29% increase in morphine AUC, likely via inhibition of intestinal P-glycoprotein.2723
Monitor for signs/symptoms of opiate toxicity.
Substrate and inhibitor of CYP3A4.
May be coadministered with omeprazole or ranitidine.
Darunavir is an inhibitor of CYP3A4. Darunavir/r may induce CYP2C9, 2C19. Darunavir/r may possibly inhibit CYP2D6.
Prezista®:
For treatment-experienced patients: 600/100 mg ritonavir po BID with food.
For treatment naïve patients or those with no darunavir resistance-associated mutations (RAMS): 800/100mg ritonavir po once daily with food.
In a multicentre open-label study (n=100) patients virally suppressed on darunavir 800/100 mg QD plus 2 NRTIs were randomized to continue on darunavir 800/100 mg QD or switched to darunavir 600/100 mg QD. At week 48, darunavir Ctrough levels were similar between treatment arms and the reduced darunavir dose showed non-inferior virologic efficacy to the standard dose arm. CD4 cell counts remained stable in both groups.2950
Prezcobix®: 1 tablet daily with food.
Symtuza®: 1 tablet daily with food.
Adult population PK (HIV-positive subjects):
Pediatric population PK:
Darunavir 800mg/100mg daily for 7 days: conc remained above the protein-binding corrected in-vitro EC50 55ng/ml for ≥ 48 hours in healthy volunteers after last dose was administered.2931
Based on PK sampling data from the GRACE study, exposure to darunavir was not influenced by age, body weight, hepatitis B co-infection status, or use of etravirine or tenofovir. There were no clinically relevant differences in exposure to darunavir according to race or gender2945. In healthy volunteers (n=23) who had previously participated in a pravastatin-darunavir/ritonavir interaction study, CYP3A5 and ABCB1 polymorphisms were not associated with variability in darunavir/ritonavir pharmacokinetics.2961
Darunavir concentrations were compared in 34 time-matched blood plasma and seminal plasma samples from 18 HIV-positive men. Good penetration of darunavir into the seminal fluid was observed, with concentrations approximately 10-20% of blood plasma levels. All seminal plasma darunavir were above the protein-corrected EC50 values for wild-type HIV-1 (55 ng/mL), and a third of all seminal plasma darunavir levels exceeded the protein-corrected EC50 required to inhibit protease inhibitor resistant HIV-1 (550 ng/mL).2959
Intracellular darunavir concentrations are approximately 5-times higher than plasma concentrations, and are significantly correlated with plasma ritonavir exposures2939. In healthy volunteers who received either darunavir 900/100 mg QD or efavirenz 600 mg QD alone or in combination, intracellular concentrations of both darunavir and efavirenz were significantly increased when the drugs were coadministered: intracellular darunavir AUC ↑ 124% and Cmax ↑ 163% and intracellular efavirenz C24h ↑ 139%.2957
In a cross-sectional TDM database review of non-pregnant HIV-infected adults taking darunavir 800/100 mg QD, darunavir C24h obtained after morning dosing were significantly higher than those after evening dosing (1632 vs 1433 ng/mL, respectively, p < 0.0001). The difference was more pronounced in women vs. men. Findings may represent Circadian variation in hepatic CYP3A4, intestinal P-gp and gastrointestinal mobility.2952
Bioequivalence demonstrated with 800 mg darunavir tablet to two 400 mg darunavir tablets, both given with ritonavir 100 mg.2946
Bioequivalence demonstrated with darunavir 800/cobicistat 150 mg fixed dose tablet to darunavir and cobicistat administered as single agents under fasted and fed conditions.2948
Parent: UGT. Active metabolite: morphine-6-glucuronide (renal). Morphine and morphine-6-glucuronide are also P-glycoprotein substrates.
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The information in this website/app is intended for use by and with experienced physicians and pharmacists. The information is not intended to replace sound professional judgment in individual situations, and should be used in conjunction with other reliable sources of information. Due to the rapidly changing nature of information about HIV treatment and therapies, users are advised to recheck the information contained herein with the original source before applying it to patient care. Decisions about particular medical treatments should always be made in consultation with a qualified medical practitioner knowledgeable about HIV-related illness and the treatments in question.
Neither Toronto General Hospital, Alberta Health Services, the Ottawa Hospital, nor the authors and contributors are responsible for deletions or inaccuracies in information or for claims of injury resulting from any such deletions or inaccuracies. Mention of specific drugs, drug doses or drug combinations within this website does not constitute endorsement by the authors, Toronto General Hospital, Alberta Health Services or the Ottawa Hospital.
The opinions expressed herein are those of its authors and do not necessarily reflect the views and opinions of Abbvie, Gilead Canada, Merck Canada Inc., and ViiV Healthcare.
We emphasize that program only checks for interactions between HIV or HCV drugs and other drugs, it will NOT check for interactions between sets of non-HIV or HCV drugs.
Also, program content focuses primarily on pharmacokinetic based interactions, and will not include comprehensive data on pharmacodynamics interactions, including QT prolongation.
Last updated: January 10, 2016
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