Overview Of Direct Acting Antiviral Drug Interactions
The introduction of direct acting antiviral agents for treatment of hepatitis C viral infections has achieved high virological cure rates encouraging more patients to start thetreatment. However, the wide use of combined DAAs regimens offers a possibility of exposure to drug interactions especially in patients under treatment for other co-morbidities. It is not only important to monitor for drug-drug interaction during HCV therapy with DAAs, but also to evaluate the interaction potential even before the start of treatment course in order to limit the drug interaction. Indeed, this is a complex issue given the large number of drug classes that may be prescribed or non-prescribed and the combined DAAs regimens particularly those including protease inhibitors. Moreover, the disease stage of liver that itself is the target for DAAs therapy and is the common site of drug-drug interactions. Direct acting antiviral could be a victim, as they are substrates and/or a culprit and they may act as enzyme inhibitors or inducers in drug-drug interactions. Because DAAs are recently approved, most of the available data comes from in vitro research and there is a limitation in available clinical data regarding these drugs. With regard to this complex issue, there are online websites that provide help tools for the clinicians in exploring potential drug-drug interactions .
New Drugs Cure Hepatitis C
Hepatitis C is a that can cause serious and permanent liver damage. The goal of treatment is to clear the virus from the body and stop, slow and prevent liver problems. Until recently, doing that involved inconvenient and painful injections of interferon and a pill called ribavirin. That therapy is known for its toxic side effects and has been compared to low-grade chemo. Worse, it doesnt always work that well. These traditional drugs offer a 50% cure rate at best.
But today, were witnessing a revolution in hepatitis C treatment, as more and more medications that directly target the virus gain approval. These medications offer a cure, instead of a partial clearing of the virus. And, as a bonus, most come in the form of a pill. They have fewer side effects and work much fasterwhich means you dont have to stay on treatment as long as compared to interferon and other drugs.
The rapidly-evolving hep C medication list is giving new hope for the 3.2 million Americans living with the chronic form of the disease. Antiviral therapy for hep C continues to rapidly evolve with the introduction of new drugs and treatment regimens that vary based on hep C genotype, previous treatments, and the presence of cirrhosis. Heres a closer look at some of the currently prescribed interferon-free medicines for hepatitis C.
Are There Ways To Cure Hepatitis C Other Than With Medications
Patients sometimes ask whether there are ways to treat hepatitis C other than taking medicines. Currently, there are no vaccines to prevent hepatitis C. Once a person is infected, the only way to treat it is with prescribed antiviral medications.
Some patients worry that having hepatitis C means they will need a liver transplant. Only a very small fraction of people with hepatitis C require a liver transplant. By far, most people with hepatitis C never need a liver transplant. A transplant is performedonlywhen damage to the liver is extremely advanced and the liver is unable to perform its basic functions. A transplant provides a new working liver, but a transplant does not get rid of the hepatitis C virus in the patient. Patients with a liver transplant still need antiviral medication to cure their virus.
What Does It Mean To Have A Successful Treatment What Is A Sustained Virologic Response
In an untreated state, the hepatitis C virus infects the cells of the liver and then continuously lives there, making copies of itself that circulate in the bloodstream. Antiviral medications can destroy the ability of the virus to reproduce, so the amount of virus in the bloodstream then decreases. The amount of virus in the blood is measured by aviral load.
Treatment is successful when the viral load drops toundetectablelevels, which means the virus cannot be detected in the bloodstream at all. The viral load becomes undetectable during treatment and remains undetected after treatment has ended. If there is still no detectable virus in the blood 12 weeks after the end of the treatment, the treatment was successful. This is called a Sustained Virologic Response .
A patient who has achieved an SVR is considered to be cured of the hepatitis C virus.
Treatments For Hepatitis C
The goal of treatment is a virological cure . This is defined as undetectable viral RNA in plasma 24 weeks after treatment has finished. A sustained virological response prevents the development of cirrhosis. In patients who already have cirrhosis, a sustained virological response reduces the risks of liver failure and hepatocellular carcinoma.
TABLE 3 TGA-approved interferon-free regimens for hepatitis C
F0-3 METAVIR fibrosis stage 0-3
F4 METAVIR fibrosis stage 4
* Not listed on the Pharmaceutical Benefits Scheme at the time of writing.
Response rate was defined as proportion of patients with a sustained virological response measured at 3 or 6 months after the end of treatment.
8 weeks may be considered in treatment-naïve patients with no cirrhosis and a baseline viral RNA concentration < 6 x 106 IU/mL.
§ 24 weeks is recommended for patients who have failed treatment with peginterferon + ribavirin with or without a protease inhibitor.
# 24 weeks is recommended for patients who have had a previous null response to peginterferon + ribavirin, defined by a decrease in the viral RNA level of < 2 log10 IU/mL at week 12 or < 1 log10 IU/mL at week 4 during previous peginterferon + ribavirin treatment.
Don’t Miss: Hepatitis C Viral Load Quest
What Are The New Hepatitis C Treatments And When Will They Be Available
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 will be available on the Pharmaceuticals Benefits Scheme from 1 March 2016.
What Is The Dosage For Daas
- 800 mg is taken three times a day, and simeprevir 150 mg is taken once daily with food, combined with ribavirin.
- Technivie is given with ribavirin for 12 weeks for genotype 4 chronic hepatitis C virus infection without cirrhosis.
- Each tablet contains 12.5 mg ombitasvir, 75 mg paritaprevir and 50 mg ritonavir.
- Two tablets are taken every morning, with ribavirin dosed by weight: 1000 mg per day for patients weighing less than 75 kg, and 1200 mg per day for those 75 kgs and over this is divided into a twice-daily dose with food.
- Viekira is used for genotype 1a or 1b chronic hepatitis C, including people with or without cirrhosis and no liver failure symptoms.
- Viekira Pak is ombitasvir 12.5 mg, paritaprevir 75mg, ritonavir 50 mg in each tablet, packaged with dasabuvir 250mg tablets.
- It is dosed as two ombitasvir, paritaprevir, ritonavir tablets once daily and one dasabuvir tablet twice daily , along with a meal.
- It is given with or without ribavirin .
- Genotype 1a is most resistant to treatment, so Viekira is given with ribavirin for 12 weeks if there is no cirrhosis, or 24 weeks if there is cirrhosis.
- Genotype 1b is usually treated with Viekira alone for 12 weeks if no cirrhosis with cirrhosis it must be given with ribavirin for 12 weeks.
- Viekira may also be used in liver transplant recipients.
Recommended Reading: Can You Cure Hepatitis A
Another Potential Curative Drug For People With Chronic Hepatitis C Will Be Made Available On The Nhs
New draft guidance published today from NICE recommends elbasvir-grazoprevir – one of the newer hepatitis C antiviral drugs that can offer patients more effective treatment.
In clinical trials, elbasvir-grazoprevir showed cure rates above 90% for people with genotypes 1 and 4. The cure rate is dependent on the genotype, treatment history and presence of liver damage.
Professor Carole Longson, director of the NICE centre for health technology evaluation, said:Treating chronic hepatitis C had previously been a major challenge with patients having to experience long and unpleasant courses of treatment.
Elbasvir-grazoprevir, like other newer direct acting anti-viral treatments, is a drug that provides considerable health benefits to patients without some of the adverse side effects associated with earlier anti-viral treatments, such as peginterferon alpha with ribavirin.
A 12-week course of treatment with elbasvir-grazoprevir usually costs £36,500 per patient, but the NHS will pay less than this as the company has offered a confidential discount.
Taken once daily, the tablet could treat around 4,000 patients in the first year, alongside other options already available for hepatitis C.
Professor Longson continued:Our positive recommendation for elbasvir-grazoprevir means that more treatment options will become available to patients with hepatitis C. And as these types of anti-viral drugs are more effective, the spread of the virus can be reduced.
What Is Hepatitis C Again
Hepatitis C is a liver infection caused by the hep C virusand the disease is quite common. Its the most common chronic blood-borne infection in the United States. According to the U.S. Department of Health and Human Services, anywhere from 2 million to 2.8 million Americans live with chronic hepatitis C. That number could be much higher, given that many people who have hep C are asymptomatic and unaware that they are even infected.
You cant catch it from kissing, holding hands, or even if someone sneezes in your face. Hep C is passed on when infected blood gets into your bloodstream, which can happen in different ways, but typicals modes of transmission are:
Sharing needles or sharing straws to snort drugs
Working in healthcare
Sharing razors, toothbrushes, or nail clippers with an infected person
Getting a body pierce or tattoo in an unsterile environment
Getting a blood transfusion or organ transplant before the virus was discovered in 1989, or prior to 1992, when blood wasnt as thoroughly screened
Being born to a mother who had hep C when she was pregnant
While 30% of people who have hep C clear the infection through their own immune system, 70% dont, and treatment is crucial. When its left to linger, hep C can lead to serious liver complications.
Read Also: Could I Have Hepatitis And Not Know It
Challenges And Future Direction Of Daa
Though DAA has provided much needed, safe and effective therapeutic option for chronic HCV patient, some challenges need further effort. Such challenges include the presence of resistant variance, low efficacy in cirrhotic patients, presence of drug-drug interactions, and the cost. The future direction should go through multiple directions, for example, continuous monitoring and developing DAA, use of combined groups of DAA with different mechanisms of action to minimize resistance, searching for other antiviral groups with different mechanisms of action, and finding a solution for improving cirrhosis by developing antifibrotic drugs. A recent study showed promising results in the possible incorporation of a new cyclophilin inhibitor, STG-175 in DAA-regimen.
Proinflammatory Cytokines Induce Depression
Mercifully, for patients with hepatitis C, treatment with the cytokine interferon IFN-alpha has been supplanted by more effective and tolerable treatment options. But during the years of its clinical hegemony, IFN-alpha provided a unique model system for understanding behavioral and biological responses to chronic inflammation relevant to depression. Results from many studies have been quite consistent in demonstrating that IFN-alpha exposure produces a widespread increase in depressive and anxious symptoms, with a sizable minority of patients meeting full criteria for major depressive disorder within a month of commencing treatment. As reviewed in Miller and Raison , IFN-alpha treatment also produces all known biological changes associated with MDD more generally, including increased circulating pro-inflammatory cytokines, disruption of the diurnal cortisol rhythm and induction of glucocorticoid resistance, altered sleep physiology, and changes in monoamine metabolism, with many of these changes associating with increased depression during treatment . Supporting these findings are studies showing that even a single exposure to inflammatory stimuli induces depressive symptoms and depressive-style social cognitions in healthy volunteers, with these effects being strongest in women .
Anton Pozniak, in, 2010
You May Like: Ok Google How Do You Get Hepatitis C
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.
What Happens If Hep C Meds Dont Work
In rare cases , the body wont respond to either medication. If this happens, your doctor may prescribe a more potent combination of antivirals such as those found in Vosevi.
This medication blends three anti-viral meds: sofosbuvir, velpatasvir, and voxilaprevir. Because its more powerful, it may have a higher burden of side effects like headache, fatigue, diarrhea, and nausea.
Dosage entails one pill taken once a day with food for 12 weeks. Your doctor may also keep you on the meds longer to clear the infection.
Read Also: Hepatitis B Foundation Drug Watch
Why Cure Hep C
Curing your hep C clears the virus from your body. It reduces liver inflammation and can help reverse fibrosis and even cirrhosis.
Live free from the worry of hep C knowing that you no longer have hep C can help you feel better about yourself. For example, you may no longer feel worried about passing hep C to other people. There has been no better time to think about hep C treatment.
Find out more about the benefits of clearing hep C call the Hepatitis Infoline.
Grace talks about her experience of being cured of hepatitis C with new, highly effective treatments. Theres never been a better time to be cured of hep C.
What Daa Drugs Are Available
The currently available DAA agents include the following combination drug brands:
- Harvoni: This is a combination of ledipasvir and sofosbuvir. Harvoni is an NS5B nucleotide polymerase inhibitor and NS5A polymerase inhibitor.
- Zepatier: This combines elbasvir and grazoprevir. Zepatier is an NS3/4A protease inhibitor and NS5A polymerase inhibitor.
- Epclusa: This is a combination of sofosbuvir and velpatasvir. Epclusa is an NS5B nucleotide polymerase inhibitor and NS5A polymerase inhibitor.
- Vosevi: This combines sofosbuvir, velpatasvir, and voxilaprevir. Vosevi is an NS3/4A protease inhibitor, NS5B nucleotide polymerase inhibitor, and NS5A polymerase inhibitor.
- Mavyret: This is a combination of glecaprevir and pibrentasvir. Mavyret is an NS3/4A protease inhibitor and NS5A polymerase inhibitor.
Sovaldi is an NS5B polymerase inhibitor, suitable for people with the 1, 2, 3, or 4 HCV genotype without cirrhosis. It can also treat HCV in those under the age of 3 years with genotypes 2 or 3 without cirrhosis.
Healthcare professionals will prescribe Sovaldi alongside antiviral agents, such as RBV. RBV is an antiviral prescription drug to treat HCV.
Other DAA agents include:
90% of cases.
The study followed 51,478 people with HCV who were receiving Medicare. DAA treatment led to a significant decrease in mortality rates in people with and without cirrhosis.
Recommended Reading: What Medication Is Used To Treat Hepatitis C
How Do You Treat Hepatitis C
Treatment for hep C has come a long way. Patients used to require weekly interferon injections that required a course of six months to a year. Now, meds are in the form of a tablet thats taken over just a few weeks. Better yet, 80% of patients taking hep C meds report no side effects. Those who do experience them say theyre extremely mild and can be managed with OTC medications.
The beauty of todays treatments is that they can cure even chronic hep C cases that have been around for decades. Though these meds can eliminate the virus from a patients system, they cant cure damage already done to the liver or reverse liver cancerthose more serious complications will often require a separate course of treatment.
Actions For This Page
- 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.
Recommended Reading: How Easy Is It To Get Hepatitis C
Is There A Vaccine For Hepatitis C
There are no vaccinations that prevent the hepatitis C virus. Vaccinations for hepatitis A and B, however, are given to patients with HCV to prevent the possibility of acquiring another hepatitis virus. Getting hepatitis A or hepatitis B on top of hepatitis C can add liver damage or even cause severe hepatitis. People with hepatitis C should be screened for past infection with hepatitis A and B. If they have no evidence of antibodies, they should receive vaccines for hepatitis A and/or B.
Hepatitis A vaccine may be given alone or in combination with hepatitis B vaccine, depending on whether the patient needs one or both. Hepatitis A vaccine is inactivated hepatitis A virus that stimulates the immune system to develop antibodies against hepatitis A. These antibodies kill the virus before it can cause infection. It is given in 2 doses intramuscularly 6 months apart.
Hepatitis B vaccine is made with hepatitis B antigens that stimulate antibodies against the hepatitis B virus. There is no live virus in the vaccine. It is given in 3 doses intramuscularly the second dose is given 1-2 months after the first, and the last is given 6 months after the first dose. The A and B vaccine is a combination of the above and is dosed in the same way as the Hepatitis B vaccine. It is available under the brand name Twinrix.