Thursday, September 22, 2022

Antiviral Medications For Hepatitis C

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Pharmacology of Antivirals (Hep C, Herpes)
  • Recent advances in antiviral treatment have led to the development of new highly effective drugs for the treatment of all types of hepatitis C.
  • The new hepatitis C treatments are sofosbuvir with ledipasvir sofosbuvir daclatasvir and ribavirin .
  • These new treatments are now available on the Pharmaceuticals Benefits Scheme.

What Are Genotypes And Do They Matter

Six different genotypes of hepatitis C have been identified. Genotypes 1 and 3 are the most common causes of hepatitis C in Australia and make up 90 per cent of all cases. They are important because they help determine the treatment you need. Unlike in the past, however, your genotype is not important in terms of the chance of cure. With the treatment drugs, all six genotypes have a very high chance of cure.

Important Side Effects And Drug Interactions

Sofosbuvir is generally well tolerated its more common side effects include mild nausea, headache, and insomnia . The combination of sofosbuvir with amiodarone can cause life-threatening bradycardia . The addition of NS5A inhibitors does not lessen tolerability to any clinically relevant extent . Therapeutic elevation of the gastric pH lessens the bioavailability of ledipasvir, and thus the concomitant administration of sofosbuvir/ledipasvir with a proton pump inhibitor in a high dose is not recommended .

The side-effect profile and drug-interaction spectrum of the NS3/4A protease inhibitors are more complex. Simeprevir can evoke both nonspecific side effects and photosensitivity reactions patients should be advised to avoid direct exposure to sunlight and to use a topical sunscreen . All of the approved NS3/4A protease inhibitors can mildly or moderately elevate bilirubin and transaminase levels . A simultaneous, clinically relevant rise of both the bilirubin concentration and the transaminase concentrations is rare but presumably reflects hepatotoxicity and must be followed by discontinuation of the the protease inhibitor. The characteristic side effects of ribavirin are hemolytic anemia, dyspnea, an irritative cough, reduced exercise tolerance, and skin rash . As hemolysis elevates the bilirubin concentration as well, rises in bilirubin levels are more pronounced when ribavirin and NS3/4A protease inhibitors are given simultaneously.

Drug interactions

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Understanding Hepatitis C Genotypes

There is a range of medications for hepatitis C because no single drug works for everyone.

Medications may vary depending on the amount of liver scarring a person has and the viruss genotype.

A genotype refers to the genes that make up the hepatitis C virus. All genotypes cause similar liver damage, but the long-term effects may differ.

Hepatitis C has seven genotypes. Doctors represent these types by using the numbers 1 to 7. The genotype is type 1 hepatitis C. There are also subgroups within these groups, such as hepatitis 1a and 1b.

Knowing which genotype a person has is crucial in getting the proper treatment.

suggests ribavirin effectively treats several genotypes, but it does not work on its own. So the doctor will prescribe another medication to take with ribavirin to treat hepatitis C.

Other facts about ribavirin include:

  • Treatment duration depends on other drugs a person is taking.
  • The dosage depends on the persons body weight.
  • A person will need their blood levels frequently checked while taking the medication to monitor efficiency and toxicity.
  • Ribavirin may also cause congenital anomalies. Avoid ribavirin while pregnant or if trying to conceive.

Combination drugs tend to be effective for most or all hepatitis C genotypes.

Contaminated Needles And Infected Blood

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You can get hepatitis C from sharing contaminated needles, syringes and other injecting equipment during recreational drug use. Banknotes and straws used for snorting may also pass the virus on.

Being exposed to unsterilised tattoo and body piercing equipment can also pass hepatitis C on. Occasionally, you can get it from sharing a towel, razor blades or a toothbrush if there is infected blood on them.

Hepatitis C infection is also passed on in healthcare settings, from needle stick injuries or from medical and dental equipment that has not been properly sterilised. In countries where blood products are not routinely screened, you can also get hepatitis C by receiving a transfusion of unscreened blood and blood products.

You can prevent hepatitis C by:

  • never sharing needles and syringes or other items that may be contaminated with infected blood
  • only having tattoos, body piercings or acupuncture in a professional setting, where new, sterile needles are used
  • following the standard infection control precautions, if youre working in a healthcare setting.

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Will The Drugs Be Available By 1 March 2016

Although the drugs will be available for prescribing through the Pharmaceutical Benefits Scheme, it may be that not all GPs or pharmacists are fully aware of the new treatments by that date. This means there may be some delay in some areas in accessing the drugs from your local GP. However, the Victorian Government is working with doctors, services and hospitals to ensure these delays are minimised as much as possible.

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Quality Of The Evidence

Due to the lack of studies on the topic that combined antiviral treatment with other interventions or RCTs that evaluate new antivirals that during last year has been demonstrated to be the goldstandard to treat HCV infection, our conclusions must be considered cautiously because of several potential limitations in the available data.

We are aware that the width of the CIs could reflect a lack of statistical power which is directly related to the sample size of the included studies that evaluated the same outcomes that could be metaanalysed.

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What Can People Do To Help The Medications Work Best

  • Take the medications every day
  • Stay in touch with pharmacy to be sure that all refills are ready on time
  • Take the medications exactly as prescribed
  • Do not skip doses
  • Get all blood tests done on time
  • Go to all visits with providers as recommended
  • Tell the provider about all other medications that are being taken – including over-the-counter medicines, vitamins, herbs, and supplements
  • Complete the entire course of medication

Protease Inhibitor Antiviral Medications

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Protease inhibitors work by preventing the spread of infection within the body by stopping viruses from multiplying.

Grazoprevir is a protease inhibitor for hepatitis C genotypes 1 and 4. Its only available in combination with elbasvir and sold as grazoprevir/elbasvir.

The drug combination is sold under the brand name Zepatier.

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Study Underscores The Powerful Effect Of Direct

Date:
Henry Ford Health System
Summary:
Researchers report that patients with chronic hepatitis C who are treated with direct-acting antiviral medicines are less likely to be hospitalized or seek emergency care for liver and non-liver related health issues. The study underscores the extraordinary effect of these newer antivirals, which have been shown to cure hepatitis C in 98 percent of patients who take them.

Researchers at Henry Ford Health System, as part of a national hepatitis C collaborative, report that patients with chronic hepatitis C who are treated with direct-acting antiviral medicines are less likely to be hospitalized or seek emergency care for liver and non-liver related health issues.

The study, published online in Clinical Infectious Diseases, underscores the extraordinary effect of these newer antivirals, which have been shown to cure hepatitis C in 98 percent of patients who take them. Patients are said to be cured when the virus is no longer detectable in their blood.

“The findings of our study show that curing hepatitis C not only gets rid of the virus, it also improves the overall health of patients,” said Stuart Gordon, M.D., Director of the Division of Hepatology at Henry Ford and the study’s lead author. “This is consistent with our earlier studies that showed effective treatment of hepatitis C also reduces the risk of patients developing other health conditions like diabetes, kidney disease, stroke and heart attacks.”

Key findings of the study:

Where Can I Go If I Have Further Questions Or Need More Information

  • Your local GP and pharmacist can provide you with more information on the new treatments, including if they are right for you. To find a GP, please click here
  • The Victorian Government funds a range of community organisations to provide information, care and support to people living with hepatitis C, and on the new treatments. For more information, please visit:
  • Hepatitis Victoria’s website or their Hepatitis Infoline on 1800 703 003or refer to the Hepatitis Victoria, PBS factsheets

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Current Antiviral Treatment Strategies

The introduction of DAA revolutionized the field of antiviral therapy for patients chronically infected with HCV. Antiviral therapy usually consists of at least two antiviral substances from different drug classes with different modes of action . Treatment decisions are based on genotype , presence of cirrhosis and response to prior treatments . Typical treatment regimens for patients with and without compensated cirrhosis are depicted in Tables 1 and 2. All different recommended regimens achieve SVR rates of more than 95% if administered correctly .

Table 1.

Treatment of patients with chronic hepatitis C without cirrhosis

Table 2.

Treatment of patients with chronic hepatitis C with compensated cirrhosis

Fig. 1.

The replication cycle of the hepatitis C virus and modes of action of direct-acting antivirals are displayed .

The pangenotypic drug combinations sofosbuvir/velpatasvir and glecaprevir/pibrentasvir show high antiviral efficacy against all HCV genotypes. Treatment duration differs from 8 weeks for glecaprevir/pibrentasvir in noncirrhotic treatment-naive patients to 12 weeks for patients with liver cirrhosis or 16 weeks for GT 3 patients with liver cirrhosis and/or prior treatment failure. Sofosbuvir/velpatasvir has to be administered for 12 weeks independently of fibrosis level . Treatment with grazoprevir/elbasvir is possible in patients with GT 1 or 4 infection and has to be administered for 1216 weeks depending on GT, fibrosis stage and viral load .

Willowbrook State School Experiments

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A New York University researcher named Saul Krugman continued this research into the 1950s and 1960s, most infamously with his experiments on mentally disabled children at the Willowbrook State School in New York, a crowded urban facility where hepatitis infections were highly endemic to the student body. Krugman injected students with gamma globulin, a type of antibody. After observing the temporary protection against infection this antibody provided, he then tried injected live hepatitis virus into students. Krugman also controversially took feces from infected students, blended it into milkshakes, and fed it to newly admitted children.

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Antiviral Medication For Hepatitis C

For people with hepatitis C, the goal of treatment with antiviral medication is to prevent the virus from replicating, or copying itself, and to eliminate the virus from the bloodstream. If the hepatitis C virus has been in the body for more than six months, the infection is considered chronic. Without treatment, most people with acute hepatitis C develop the chronic form of the disease.

Your doctor decides which antiviral medicationor combination of medicationsto prescribe based on the results of a blood test called a genotype test. There are six genotypes, or strains, of the hepatitis C virus, and people with certain genotypes respond more quickly to medical treatment.

For many years, the standard treatment for chronic hepatitis C consisted of the antiviral medications pegylated interferon and ribavirin. Ribavirin is taken by mouth every day, and interferon is an injection that you or a caregiver can administer once a week at home.

In 2013 and 2014, the U.S. Food and Drug Administration approved a group of new medications for the treatment of hepatitis C. These medications, which include sofosbuvir, are very effective and have fewer side effects than older medications, particularly interferon.

How Is Viral Hepatitis Prevented

Prevention of hepatitis involves measures to avoid exposure to the viruses, using immunoglobulin in the event of exposure, and vaccines. Administration of immunoglobulin is called passive protection because antibodies from patients who have had viral hepatitis are given to the patient. Vaccination is called active protection because killed viruses or non-infectious components of viruses are given to stimulate the body to produce its own antibodies.

Avoidance of exposure to viruses

Use of immunoglobulins

Immune serum globulin is human serum that contains antibodies to hepatitis A. ISG can be administered to prevent infection in individuals who have been exposed to hepatitis A. ISG works immediately upon administration, and the duration of protection is several months. ISG usually is given to travelers to regions of the world where there are high rates of hepatitis A infection and to close or household contacts of patients with hepatitis A infection. ISG is safe with few side effects.

Hepatitis A

Individuals at increased risk of acquiring hepatitis A are:

Some local health authorities or private companies may require hepatitis A vaccination for food handlers.

Hepatitis B

In the United States, injecting drugs is the most common way that people get hepatitis C.13

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How Do Doctors Treat The Complications Of Hepatitis C

If hepatitis C leads to cirrhosis, you should see a doctor who specializes in liver diseases. Doctors can treat the health problems related to cirrhosis with medicines, surgery, and other medical procedures. If you have cirrhosis, you have an increased chance of liver cancer. Your doctor may order an ultrasound test to check for liver cancer.

If hepatitis C leads to liver failure or liver cancer, you may need a liver transplant.

Do You Need Vaccinations Before Traveling Abroad

Pharmacology – ANTIVIRAL DRUGS (MADE EASY)

The CDC divides travel vaccinations into three categories: 1) routine, 2) recommended, and 3) required. The only vaccine classified as required by International Health Regulations is the yellow fever vaccination for travel to certain countries in sub-Saharan Africa and tropical South America.

Routine vaccinations are those that are normally administered, usually during childhood, in the United States. These include immunizations against:

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What About Patients With Hepatitis C Who Also Have Hepatitis B

Hepatitis B virus can flare in patients who are co-infected with hepatitis B and hepatitis C and are taking medication for hepatitis C. This has been reported as a potential risk for patients who are taking hepatitis C treatment and have underlying hepatitis B as well. The flare usually occurs within a few weeks after the patient starts taking medication for hepatitis C. Therefore, patients who have both hepatitis B and hepatitis C should be seen by a hepatitis expertbeforestarting treatment of the hepatitis C they may need to start taking hepatitis B treatment to avoid a hepatitis B flare.

Recommended Monitoring For Pregnancy

RECOMMENDED RATING Women of childbearing potential and their partners should not receive ribavirin during or for at least 6 months prior to pregnancy. I, C Women of childbearing potential should be counseled not to become pregnant while receiving a ribavirin-containing antiviral regimen, and for at least 6 months after stopping the regimen. I, C Male partners of women of childbearing potential should be cautioned to prevent pregnancy while they are receiving a ribavirin-containing antiviral regimen, and for up to 6 months after stopping the regimen. I, C Serum pregnancy testing is recommended for women of childbearing potential prior to beginning treatment with a regimen that includes ribavirin. I, C Assessment of contraceptive use and of possible pregnancy is recommended at appropriate intervals during ribavirin treatment for women of childbearing potential, and for female partners of men who receive ribavirin treatment. I, C

Ribavirin causes hemolysis. Patients receiving ribavirin should have hemoglobin levels checked during treatment, often after 2 weeks, and the ribavirin dose reduced if the patient develops significant anemia, often defined as hemoglobin < 10 g/dL.

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How Will My Provider Monitor Me During The Treatment

Your provider will meet with you during treatment to review how well you are tolerating treatment and review laboratory results. Laboratory tests help keep tabs on your health, track the viral load, and determine your response to treatment. You will be given specific dates to go get your blood tested at the lab during and after the treatment.

Recommended Monitoring For Patients In Whom Treatment Failed To Achieve A Sustained Virologic Response

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RECOMMENDED For patients with cirrhosis, endoscopic surveillance for varices should be performed in accordance with the AASLD guidance on portal hypertension bleeding in cirrhosis. Guidanceb a For, please refer to the appropriate section.b Unlike the AASLD/IDSA HCV guidance, the AASLD guidelines use the GRADE system to rate recommendations please see that document for further information about this rating system.

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Limitations Of Drug Treatments

Though the latest generation of hepatitis C drugs can effectively cure the disease, patients whose hepatitis C infection has progressed to the point of causing advanced cirrhosis or liver failure may require a liver transplant to fully recover.

Its important to let your doctor know what other medications and supplements youre taking so you can avoid harmful interactions. If youre nursing or pregnant, youll also want to let your healthcare provider know, as this can affect your treatment options.

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Pegylated Interferon Alfa And Ribavirin

The standard treatment regimen for chronic HCV infection is outlined in Table 1. Pegylated interferon alfa-2a and pegylated interferon alfa-2b are modified forms of interferon alfa with much longer half-lives, which allow these drugs to be taken once a week. In addition, they are significantly more effective against HCV, either alone or in combination with ribavirin , compared with unmodified interferon alfa, and they have side effect profiles similar to that of unmodified interferon alfa.6,7

The HCV viral load should be assessed after 24 weeks of therapy. Recent studies suggest that patients infected with HCV genotype 2 or 3 should receive a total course of 24 weeks of therapy, while patients with genotypes 1 or 4 have higher sustained virologic response rates if they are treated for 48 weeks. In patients with genotype 1a or 1b infection, the detection of viremia at 24 weeks predicts viral persistence despite therapy. Thus, it is recommended that patients with viremia at 24 weeks discontinue therapy. Because viremia at 12 weeks now appears to predict persistent HCV infection, some experts recommend discontinuing therapy at 12 weeks if HCV viremia is detected. In patients with genotype 1a or 1b and an undetectable HCV viral load at 24 weeks, continuation of therapy for the full 48-week course is indicated.

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