Liverpool HEP Interactions

Potential Weak Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Buprenorphine

Summary:

Buprenorphine can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no a priori dose alteration is required. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Coadministration with buprenorphine (4-24 mg once daily) and naloxone (1-6 mg once daily) increased buprenorphine Cmax, AUC and Cmin by 2.18-, 2.07- and 3.12-fold, respectively; values for norbuprenorphine increased by 2.07-, 1.84- and 2.10-fold, respectively. These changes in PK values did not translate into any pharmacodynamic changes. There was no change in exposure of ombitasvir, paritaprevir or dasabuvir based on cross-study comparison. However, prescribers should be aware to look out for signs of sedation and cognitive effects, particularly on initiation and discontinuation of treatment.

Description:

Coadministration with buprenorphine (4-24 mg once daily) and naloxone (1-6 mg once daily) increased buprenorphine Cmax, AUC and Cmin by 2.18-, 2.07- and 3.12-fold, respectively; values for norbuprenorphine increased by 2.07-, 1.84- and 2.10-fold, respectively. Naloxone Cmax and AUC increased by 18% and 28%. (Dose normalised parameters reported for buprenorphine and naloxone.) The increases were due to CYP3A4 inhibition by ritonavir and UGT inhibition by paritaprevir, ombitasvir and dasabuvir. There was no change in exposure of ombitasvir, paritaprevir or dasabuvir based on cross-study comparison. No dose adjustment is necessary.
Viekirax Summary of Product Characteristics, AbbVie Ltd, January 2015.
Exviera Summary of Product Characteristics, AbbVie Ltd, January 2015.

Coadministration with buprenorphine (4-24 mg once daily) and naloxone (1-6 mg once daily) was studied in 10 subjects. Cmax, AUC and Cmin of buprenorphine increased by 2.18-, 2.07- and 3.12-fold, respectively; values for norbuprenorphine increased by 2.07-, 1.84- and 2.10-fold, respectively. Naloxone Cmax and AUC increased by 18% and 28%. No dose adjustment of buprenorphine/naloxone is required upon co-administration. Patients should be closely monitored for sedation and cognitive effects.

Viekira Pak US Prescribing Information, AbbVie, December 2014.

Coadministration of ombitasvir/paritaprevir/ritonavir + dasabuvir (25/150/100 mg + 250 or 400 mg), with buprenorphine/naloxone was studied in 13 healthy volunteers enrolled on stable buprenorphine/naloxone maintenance therapy (4/1 mg- 24/6 mg). R-methadone Cmax and AUC increased by 4% and 5%, respectively, whilst S-methadone Cmax and AUC both decreased by 1%. Buprenorphine Cmax and AUC increased by 118% and 107%, respectively, while norbuprenorphine Cmax and AUC increased by 107& and 84%, respectively. Pharmacodynamic measurements (pupil diameter, opioid withdrawal score and desire for drug questionnaire score) were unaffected by coadministration. The authors state that no dose adjustment for buprenorphine/naloxone is recommended as the PK changes were not clinically relevant, as reflected in the unchanged pharmacodynamic measurements.

Menon RM, Badri PS, Wang T et al. Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir. J Hepatol, 2015, 63(1): 20-9.

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