The current standard of care for hepatitis C virus (HCV) infection in China is Peg-IFN-α in combination with ribavirin, and a significant proportion of patients are still not cured or cannot tolerate this regimen with this treatment. The rapid development of many small molecule compounds targeting viral proteins specific to the HCV life cycle has improved the efficacy of antiviral therapy. These drugs, universally named direct antiviral agents (DAAs) against HCV, include nonstructural protein (NS) 3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors, etc. Since 2011, a number of drugs in this class have been marketed in the United States and Europe, among others, as shown in the table below.
Sofosbuvir (sofosbuvir)
Some drugs, when combined with sofosbuvir, may reduce the blood levels of sofosbuvir, resulting in a decrease in the efficacy of sofosbuvir. Examples include
Anti-epileptic drugs (e.g., carbamazepine, phenytoin sodium, fosphenytoin sodium, phenobarbital, oxcarbazepine).
Anti-tuberculosis drugs (e.g., rifabutin, rifampin, rifapentine).
Anti-HIV protease inhibitors (e.g., tipranavir, ritonavir).
Some herbal drugs may also interact with sofosbuvir.
Foreign studies have found that a herb of the genus Hypericum, St. John’s wort (Kanzai lenga), which can be used to treat depression, can reduce the drug concentration of sofosbuvir in the blood when taken together with sofosbuvir, resulting in decreased efficacy.
The combination of some drugs with sofibuvir may increase the blood levels of sofibuvir, leading to adverse reactions.
A new drug for Gaucher’s disease, eliglustat, may increase the concentration of sofosbuvir, but it is not known what the consequences of combining the two drugs will be, and care should be taken to monitor the blood levels of sofosbuvir if the two drugs are used together to prevent adverse reactions. To prevent adverse reactions.
The FDA has issued a warning that there may be an interaction between sofosbuvir and amiodarone, resulting in increased blood levels of sofosbuvir and cardiotoxicity. It is recommended that sofibuvir and amiodarone not be taken together.
Some drugs do not have significant interactions with sofibuvir and can be used together. Examples include.
Cyclosporine A, tacrolimus, darunavir, rilpivirine, emtricitabine, tenofovir, efavirenz, methadone.
Some DAAs have synergistic effects with sofosbuvir and the combination can improve the efficacy of the drug. For example.
Daclatasvir, another new drug for hepatitis C, can improve the efficacy of the drug when combined with sofosbuvir and is recommended by the 2015 European guidelines for the management of hepatitis C for the treatment of all genotypes of hepatitis C virus infection.
Daclatasvir (Daclatasvir) and Asunaprevir (Asunaprevir)
Daclatasvir.
In studies conducted in in vitro trials, daclatasvir inhibited multiple genotypes of hepatitis C virus and was therefore effective in patients infected with all genotypes of hepatitis C virus. In phase I clinical studies with daclatasvir monotherapy, patients tolerated it well, and the common adverse event was headache, with no unrecognized serious drug-related adverse events. In studies of daclatasvir in combination with sofosbuvir, common adverse events were headache and nausea, and a small number of patients could experience decreased blood phosphorus and increased blood glucose.
The current study showed that daclatasvir interacts with oral contraceptives, efavirenz, atazanavir/ritonavir, omeprazole, and midazolam. You should consult your doctor before treatment with daclatasvir and avoid taking it together with some drugs that have interactions. Methadone and buprenorphine do not have significant interactions with daclatasvir, and drug users using drugs such as methadone and buprenorphine do not need to adjust their drug doses while on daclatasvir treatment.
Asunpravir.
In studies in in vitro trials, alsunpravir was effective against hepatitis C virus infections of genotypes 1, 4, 5, and 6, but was less effective in inhibiting hepatitis C virus of genotypes 2 and 3.
Asunpuvir is metabolized primarily in the liver and excreted from the feces via the bile. In clinical trials, a few patients developed abnormal liver function during treatment, but no liver failure occurred. Therefore, liver function should be monitored during treatment. The metabolism of the drug is slowed in patients with severe liver damage, so it is not recommended for patients with grade B and C cirrhosis; however, in patients with renal insufficiency, the elimination of the drug is not affected, and no adjustment of the drug dose is required in patients with renal failure or those requiring renal dialysis.
Current studies have shown interactions between Asunpravir and caffeine, cloxacin, omeprazole, dextromethorphan, midazolam (oral dose), digoxin, resuprastatin, rifampin, and ketoconazole. You should consult your doctor before treating with Asunpuvir and avoid taking it together with some drugs that have interactions.
Daclatasvir has synergistic effects with Asunpuvir.
The combination has a strong antiviral effect, gets rid of interferon and ribavirin, which have significant adverse effects, improves the safety of treatment for people infected with hepatitis C virus, and reduces viral resistance. The combination of daclatasvir and acepromazine for the treatment of genotype 1 hepatitis C virus infection can achieve a sustained viral response rate of 95% at 24 weeks; it can also achieve a sustained viral response rate of more than 80% in patients who are unsuitable for or intolerant to interferon therapy and in patients who do not respond to interferon therapy. In a phase II clinical study of daclatasvir in combination with acepromazine in patients infected with hepatitis C virus is, in addition to headache, diarrhea and mild ALT abnormalities occurred in a few patients.
Viekira Pak
Viekira Pak is only recommended for the treatment of patients infected with genotype 1 hepatitis C virus. Treatment options differ for patients infected with different subtypes of genotype 1 virus, with or without cirrhosis.
Viekira Pak not only gets rid of interferon adverse effects and the pain of frequent injections, but also shortens the previous 48-week course of interferon + ribavirin therapy to 12-24 weeks for patients with cirrhosis, and genotype 1b viral infected patients can also get rid of ribavirin therapy.
The drugs in the Viekira Pak combination are metabolized in the liver by drug-metabolizing enzymes and excreted from the body, and therefore interact with many drugs. The drugs in Viekira Pak are not excreted by the kidneys and no dose adjustment is required for patients with renal impairment.
Viekira Pak has been associated with nausea, pruritus, and insomnia. ritonavir may cause indirect bilirubin elevations in a small number of patients; asymptomatic ALT elevations may occur in a small number of patients, but they do not affect treatment and may recover after discontinuation of the drug; ribavirin-related adverse reactions may occur in patients treated with ribavirin. viekira Pak is a class B drug for safety during pregnancy. Effective contraception is recommended during treatment, but do not use contraception with drugs containing ethinyl estradiol; estrogenic drugs may increase the risk of ALT elevation. Liver function should be monitored during treatment, and treatment with Viekira Pak is not recommended for patients with decompensated cirrhosis (grades B and C of the Child-Pugh classification). There are no clinical data on the safety of Viekira Pak in children <18 years of age, so its use in children with hepatitis C virus infection should be weighed against the pros and cons.