Combined Use of Calcium-channel Blockers With Ombitasvir/Paritaprevir/Ritonavir Exacerbates Peripheral Edema in Elderly Japanese Patients

The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potent...

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Bibliographic Details
Published in:Anticancer research 2022-04, Vol.42 (4), p.2087-2093
Main Authors: Sadaka, Yuna, Soda, Midori, Hori, Akiyo, Miyahara, Yuri, Oida, Yasuhisa, Nishigaki, Yoichi, Tomita, Eiichi, Mizui, Takashi, Kitaichi, Kiyoyuki
Format: Article
Language:English
Subjects:
Antiretroviral drugs
Antiviral agents
Antiviral drugs
Calcium channel blockers
Calcium channels
Cytochrome
Cytochrome P450
Cytochromes P450
Edema
Hepatitis C
Patients
Ritonavir
Substrates
Terminology
Viruses
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Summary:The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potential adverse drug reaction possibly caused by the anti-hepatitis C virus (HCV) regimen of ombitasvir/paritaprevir/ritonavir (OPR) and CCBs. We enrolled Japanese patients prescribed OPR for HCV infection. Peripheral edema was graded according to the Common Terminology Criteria for Adverse Events ver. 4. Plasma samples were collected on days 0, 7, 14, 28, and 42 after antiviral treatment, at the trough level. Out of 52 patients, 64% experienced grade 1 or grade 2 peripheral edema, but not grade 3. Concomitant use of CCBs significantly increased the emergence of grade 2 edema (62%), compared with patients treated solely with OPR (48%). The use of OPR significantly increased the plasma concentration of amlodipine. Peripheral edema in patients treated with OPR and CCBs, although tolerable, should be closely monitored.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.15690