Management of drug interactions with direct‐acting antivirals in Dutch <scp>HIV</scp>/hepatitis C virus‐coinfected patients: adequate but not perfect

Smolders, Elise J; Smit, Colette; Kanter, C. de; Dofferhoff, A. S. M.; Arends, Joop E.; Brinkman, Kees; Rijnders, Bart J. A.; Valk, Marc van der; Reiss, Peter; Burger, David M.

doi:10.1111/hiv.12570

Cited by 12 publications

(13 citation statements)

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“…Anticonvulsant medications are reported to be potent inducers of P-glycoprotein polypeptide and cytochrome P450-CYP3A4 enzymes capable of decreasing sofosbuvir and daclatasvir plasma concentrations, respectively, leading to reduced therapeutic effect of these antivirals. [ 47 – 50 ] It is important to emphasize that in our series, the use of anticonvulsant medications was associated with therapeutic failure in all analyses performed, whether in the multivariate analysis of the 643 patients (by IIT or m-ITT) or in the separate analysis of the 520 coinfected patients, for whom we had all the clinical information related to HIV immunosuppression.…”

Section: Discussionmentioning

confidence: 95%

Effectiveness of direct-acting antivirals for hepatitis C virus infection in hepatitis C/HIV coinfected individuals

et al. 2020

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In a hepatitis C virus (HCV)/HIV-positive Brazilian cohort, evaluate the safety and efficacy of HCV DAAs, the frequency of resistance substitutions in the HCV NS5A and NS5B genes and identify predictors of treatment failure. Retrospective multicenter study of HCV/HIV patients treated with sofosbuvir (SOF)-based regimens at 10 reference centers in Brazil. Clinical and virological data were collected. Genetic diversity in the NS5A and NS5B genes was assessed by direct nucleotide sequencing. The primary outcome was sustained virological response (SVR) 12 weeks after DAA completion. Of 643 HCV/HIV patients analyzed, 74.7% were male, median CD4+ T cell count was 617 cells/mm 3 , 90% had an undetectable HIV viral load. HCV genotype 1 was detected in 80.2%, and 60% were taking at least 1 medication other than antiretroviral drugs during their DAA therapy. Cirrhosis was present in 42%. An SOF/daclatasvir (DCV) regimen was used in most patients (98%). The frequency of NS5A polymorphisms associated with clinically relevant resistance to DCV was 2%; no relevant NS5B variants were identified. The SVR12 rate was 92.8% in an intention to treat (ITT) analysis and 96% in a modified ITT (m-ITT) analysis. AE occurred in 1.6% of patients. By multivariate analysis, therapeutic failure was associated, in the m-ITT analysis, with concomitant use of anticonvulsant drugs ( P = .001), age ( P = .04), and female gender ( P = .04). SOF/DCV regimens were associated with a high SVR rate in an HCV/HIV population. The use of concurrent anticonvulsant drugs and DAAs decreases the chances of achieving an SVR.

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Section: Discussionmentioning

confidence: 95%

Effectiveness of direct-acting antivirals for hepatitis C virus infection in hepatitis C/HIV coinfected individuals

et al. 2020

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“…DAAs can be the substrates, inhibitors, or inducers of drug-metabolizing enzymes and drug transporters, which makes them both victims as well as perpetrators of DDIs [ 5 6 7 ]. Numerous studies have demonstrated that most patients with HCV infection have to undergo polypharmacy with a large number and diverse combination of medications, especially cardiovascular drugs such as the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, commonly known as statins [ 8 9 10 11 12 13 14 ]. Statins are substrates of several drug transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP), and cytochrome p450 enzyme (CYP450) [ 15 16 ].…”

Section: Introductionmentioning

confidence: 99%

Drug-drug interactions between direct-acting antivirals and statins in the treatment of chronic hepatitis C

Kuo¹,

Tseng

Lee³

et al. 2020

Tzu Chi Med J

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As the first line of treatment for hepatitis C virus (HCV) infection, direct-acting antivirals (DAAs) have greater efficacy and fewer adverse effects than other treatments; however, drug-drug interactions (DDIs) must be avoided when used in combination with other medications, such as statins. HCV patients are mostly in the need for polypharmacy, particularly the comedication of DAAs and cardiovascular drugs such as statins. This poses a risk of pharmacokinetic interactions between the two classes of drugs that may lead to severe myopathy or even rhabdomyolysis. Therefore, evaluating the severity of the DDIs and managing them is important. A multidisciplinary team-based model of care for HCV patients receiving DAAs can review the pharmacology profiles of other drugs for relevant DDIs with the DAAs, before prescription. Such a model can also follow the patients through the therapeutic cycle to make sure that their medical regimen is safe and effective. This article reviews the comedication rate and DDI-prevalence in HCV patients receiving statins along with the DAAs, details the mechanisms involved, gives recommendations for management, and shares our experience with a multidisciplinary team-based care program for the treatment of HCV patients.

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“…Numerous papers have shown that HCV patients are polypharmacy patients, meaning that they use high numbers of drugs and a diverse combination of medications [ 4 – 7 ]. This includes the usual suspects that we would expect in HCV-infected patients, such as immunosuppressive agents (liver transplantation), antiretroviral agents (HIV co-infection), and psychoactive medications, because of the high incidence of mental illnesses.…”

Section: Introductionmentioning

confidence: 99%

“…This includes the usual suspects that we would expect in HCV-infected patients, such as immunosuppressive agents (liver transplantation), antiretroviral agents (HIV co-infection), and psychoactive medications, because of the high incidence of mental illnesses. However, drugs used for cardiovascular risk management are also frequently used by HCV-infected patients, e.g., statins (HMG-CoA reductase inhibitors), anticoagulant agents, and antihypertensive drugs [ 4 – 7 ]. We can explain this by the fact that we are now treating aging HCV-infected patients, and polypharmacy has a positive correlation with age [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Risk Management and Hepatitis C: Combining Drugs

et al. 2018

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Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug–drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs. Therefore, the aim of this review was to describe DDIs between cardiovascular drugs (CVDs) and DAAs. An extensive literature search was performed containing search terms for the marketed DAAs and CVDs (β-blocking agents, ACE inhibitors, angiotensin II antagonists, renin inhibitors, diuretics, calcium channel blockers, statins/ezetimibe, fibrates, platelet aggregation inhibitors, vitamin K antagonists, heparins, direct Xa inhibitors, nitrates, amiodarone, and digoxin). In particular, the drug labels from the European Medicines Agency and the US Food and Drug Administration were used. A main finding of this review is that CVDs are mostly victims of DDIs with DAAs. Therefore, when possible, monitoring of pharmacodynamics is recommended when coadministering these drugs with DAAs. Nevertheless, it is sometimes better to discontinue a drug on a temporary basis (statins, ezetimide). The DAAs are victims of DDIs in combination with bisoprolol, carvedilol, labetalol, verapamil, and gemfibrozil. Despite there are many DDIs predicted in this review, most of these DDIs can be managed by monitoring the efficacy and toxicity of the victim drug or by switching to another CVD/DAA.

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Management of drug interactions with direct‐acting antivirals in Dutch HIV/hepatitis C virus‐coinfected patients: adequate but not perfect

Abstract: Prescription patterns suggest that physicians are aware of potential DDIs between co-medication and DAAs, in particular potential DDIs with cART. Greater awareness is needed concerning category 3 interactions between non-cART co-medication and DAAs.

Cited by 12 publications

References 12 publications

Effectiveness of direct-acting antivirals for hepatitis C virus infection in hepatitis C/HIV coinfected individuals

Effectiveness of direct-acting antivirals for hepatitis C virus infection in hepatitis C/HIV coinfected individuals

Drug-drug interactions between direct-acting antivirals and statins in the treatment of chronic hepatitis C

Cardiovascular Risk Management and Hepatitis C: Combining Drugs

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