Instructions For Use Section
| Figure C |
How should I store VIREAD powder?
- Store VIREAD powder at room temperature between 68 °F to 77 °F .
- Keep VIREAD powder in the original container.
- Keep the bottle tightly closed.
- Do not use VIREAD powder if the seal over the bottle opening is broken or missing.
Keep VIREAD and all medicines out of the reach of children.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Biological Response And Safety
The proportion of patients achieving BR was compared between TDF and ETV group, with no significant difference observed during the course of therapy. At 3, 6, 12, and 24 months, normalization of ALT was achieved in 51, 68.6, 81.8, and 83.8% patients treated with TDF and in 62.5, 79.6, 81.1, and 89.4% patients treated with ETV , respectively. The difference in ALT normalization between groups was not significant in HBeAg-positive or HBeAg negative patients. There were 4 patients in the TDF group and 2 patients in the ETV group experienced ALT flare, of whom 1 patient administrated with ETV experienced drug resistance.
We recorded baseline and maximal value of SCr in the 24-month follow-up period. There was no patient experienced AKI, with mean increase of SCr was 0.10 and 0.08 mg/dL in TDF and ETV group , respectively. Additionally, 11 and 8 of patients in the TDF and ETV group experienced transient hypophosphatemia during the treatment, but none had subjective symptoms, such as poor appetite and musculoskeletal pain. No patient was observed to cease or change antiviral therapy due to side effects during the whole treatment period.
Comparison Of Lc Complications Between The Etv And Tdf Groups
Cumulative incidence of LC-related complication requiring hospitalization is shown in Figure 2. Because the median duration of treatment in the TAF-treated group was 13.0 months, cumulative incidence, and annual incidence were analyzed only in the ETV and TDF groups. Annual incidence rate of LC-related complication was 0.601 per 100-person years in the ETV group and 0.299 per 100-person years in the TDF group, which was not a significant difference .
Fig. 2.
Cumulative incidence rates of complications associated with liver cirrhosis. ETV, entecavir TDF, tenofovir disoproxil fumarate.
During the follow-up period, 11 patients in the ETV group needed hospitalization due to LC-related complications 3 due to varices, 3 due to variceal bleeding, 3 due to ascites, 1 due to spontaneous bacterial peritonitis, and 1 due to hepatic encephalopathy. Three patients in the TDF group were hospitalized due to complications: 2 with variceal bleeding and 1 with hepatic encephalopathy.
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Low Response Rates And Nonresponders
Low vaccination response rates have been associated with obesity, smoking, immunosuppression, and advanced age. Approximately 25-50% of persons who initially do not have a vaccine response will show a response to 1 additional vaccine dose, and 50-75% of individuals will have a response to a second 3-dose series.
It is recommended that testing for anti-HBs be obtained 4-12 weeks following vaccination. Revaccinate nonresponders, with another series of 3-dose hepatitis B vaccine. Consider delaying revaccination for several months after initiation of antiretroviral therapy in patients with CD4 counts below 200 cells/mm3 or those with symptomatic HIV disease. The delay in these individuals is an attempt to maximize the antibody response to the vaccine.
Do not defer vaccination in pregnant patients or patients who are unlikely to achieve an increased CD4 count. Individuals at increased risk of severe complications due to HBV infection include those unlikely to achieve CD4 counts of 200 cells/mm3 or above after antiretroviral therapy and HIV-infected pregnant women.
A combined hepatitis A virus /HBV vaccine is licensed in many countries and offers the advantage of protection against both of these viruses at the same time. The vaccine seems to be safe, although some questions exist regarding neurologic complications.
Treatment For Antiviral Resistance In Children
The 2015 APASL guidelines recommend that tenofovir or IFN should be used for the treatment of children who develop lamivudine resistance. When adefovir resistance develops, the guidelines recommend that entecavir or tenofovir should be used if the child has no history of NA treatment before receiving adefovir .
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How Supplied/storage And Handling
VIREAD tablets are available in bottles containing 30 tablets with child-resistant closure as follows:
- 150 mg of TDF : tablets are triangle-shaped, white, film-coated, and debossed with “GSI” on one side and with “150” on the other side.
- 200 mg of TDF : tablets are round-shaped, white, film-coated, and debossed with “GSI” on one side and with “200” on the other side.
- 250 mg of TDF : tablets are capsule-shaped, white, film-coated and debossed with “GSI” on one side and with “250” on the other side.
- 300 mg of TDF : tablets are almond-shaped, light-blue, film-coated, and debossed with “GILEAD” and “4331” on one side and with “300” on the other side.
VIREAD oral powder consists of white, coated granules containing 40 mg of TDF per gram of powder and is available in multi-use bottles containing 60 grams of oral powder, closed with a child-resistant closure, and co-packaged with a dosing scoop.
Store VIREAD tablets and oral powder at 25 °C , excursions permitted to 1530 °C .
- Keep container tightly closed.
- Dispense only in original container.
- Do not use if seal over bottle opening is broken or missing.
Severe Acute Exacerbation Of Hepatitis B In Patients With Hbv Infection
All patients should be tested for the presence of chronic hepatitis B virus before or when initiating VIREAD .
Discontinuation of anti-HBV therapy, including VIREAD, may be associated with severe acute exacerbations of hepatitis B. Patients infected with HBV who discontinue VIREAD should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.
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When Can Hepatitis B Patients Stop Taking Antivirals Experts Finally Have Some Answers
With the help of antivirals, many patients today have undetectable viral load , a relatively healthy liver and cleared the hepatitis B e antigen . So when can they consider stopping their daily entecavir or tenofovir pill?
For years, experts have admitted the endgame of antiviral treatment has been ill-defined. While antivirals reduce viral load and the risk of liver damage, they rarely cure people. Recently, after years of observing patients and with the help of better diagnostic tools, experts are getting better at identifying when might be safe to stop.
Historically, in addition to reducing viral load to undetectable levels, the goals of antiviral treatment were:
- Triggering HBeAg seroconversion: About 21 percent of HBeAg-positive patients with liver damage treated with either tenofovir or entecavir for 12 months are able to lose the hepatitis B e antigen and develop the e antibody . This HBeAg seroconversion indicates the immune system is fighting the infection and slowing viral replication.
- And reducing liver damage and even clearing the hepatitis B surface antigen : About 1-3 percent of patients treated with antivirals lose HBsAg after years of treatment. This is called a functional cure. Unfortunately, if you have HBeAg-negative hepatitis B, only 1-2 percent of you will lose HBsAg after five to eight years of antiviral treatment.*
Data Collection And Definition
Data were collected from electronic medical records at the Kyung Hee University Hospital at Gangdong and included clinical information, and laboratory data. Medical history, such as LC, hypertension, diabetes mellitus, history of taking lipid-lowering agents, tuberculosis, malignancy, chemotherapy, and immunosuppressive therapy was included in the demographic data. Patients underwent routine blood chemistry test and virological assessments, including hemoglobin, platelets, international normalized ratio of prothrombin time, liver function tests, serum HBV-DNA level, and status of HBeAg every 36 months. According to our outpatient protocol, patients were also followed up every 612 months with ultrasonography and serum alpha-fetoprotein level to screen for HCC.
We calculated eGFR using the modification of diet in renal disease GFR equation as 186 × 1.154 × 0.203 × 1.212 × 0.742 . HBV DNA was measured by a quantitative polymerase chain reaction assay, and CVR was defined as an HBV DNA level below 20 IU/mL. Diagnosis of LC was clinically defined taking into account platelet count, serum albumin level, prothrombin time, international normalized ratio, and radiological image findings included splenomegaly and liver surface nodularity. Endoscopic findings such as esophageal or gastric varices were considered in the diagnosis of LC.
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Patients Coinfected With Hiv
Due to the risk of development of HIV-1 resistance, VIREAD should only be used in HIV-1 and HBV coinfected patients as part of an appropriate antiretroviral combination regimen.
HIV-1 antibody testing should be offered to all HBV-infected patients before initiating therapy with VIREAD. It is also recommended that all patients with HIV-1 be tested for the presence of chronic hepatitis B before initiating treatment with VIREAD.
Conflict Of Interest Statement
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Carcinogenesis Mutagenesis Impairment Of Fertility
Carcinogenesis
Long-term oral carcinogenicity studies of TDF in mice and rats were carried out at exposures up to approximately 16 times and 5 times those observed in humans at the therapeutic dose for HIV-1 infection. At the high dose in female mice, liver adenomas were increased at exposures 16 times that in humans. In rats, the study was negative for carcinogenic findings at exposures up to 5 times that observed in humans at the therapeutic dose.
Mutagenesis
Tenofovir disoproxil fumarate was mutagenic in the in vitro mouse lymphoma assay and negative in an in vitro bacterial mutagenicity test . In an in vivo mouse micronucleus assay, TDF was negative when administered to male mice.
Impairment of Fertility
There were no effects on fertility, mating performance or early embryonic development when TDF was administered to male rats at a dose equivalent to 10 times the human dose based on body surface area comparisons for 28 days prior to mating and to female rats for 15 days prior to mating through day seven of gestation. There was, however, an alteration of the estrous cycle in female rats.
Optimal Duration Of Na Treatment
There is no finite duration of NA treatment. In the clinical trials, NAs are usually administered for 48 weeks or more. HBeAg seroconversion is widely accepted as a therapy endpoint. The 2012 EASL guidelines and 2015 APASL guidelines recommend that NA treatment be continued for at least one year after HBeAg seroconversion occurs . In the patients with HBeAg-negative hepatitis, the continuation of NA treatment until HBsAg loss is recommended due to the high relapse rate after discontinuation .
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Established And Significant Interactions
Table 12 provides a listing of established or clinically significant drug interactions. The drug interactions described are based on studies conducted with TDF .
| Concomitant Drug Class: Drug Name | Effect on Concentration |
|---|
What Other Information Should I Know
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
Keep a supply of tenofovir on hand. Do not wait until you run out of medication to refill your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
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Hepatitis C Virus Drugs
Taking certain hepatitis C drugs with tenofovir may increase the levels of tenofovir in your body. This can cause more side effects from the drug. Examples of these drugs include:
- ledipasvir/sofosbuvir
- sofosbuvir/velpatasvir/voxilaprevir
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.
All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:
- your age
- how severe your condition is
- other medical conditions you have
- how you react to the first dose
Treatment Of Children With Acute Hbv Infection
Children with acute HBV infection are usually asymptomatic. Those with fulminant hepatitis, severe acute hepatitis and protracted acute hepatitis might benefit from NA treatment. Lamivudine, adefovir, entecavir and tenofovir are considered acceptable options. IFN is contraindicated . Although an optimal duration of NA treatment has not been established, it is recommended that NA treatment be continued until HBsAg clearance, or at least 3 months after HBsAg seroconversion, or 1 year after HBeAg seroconversion without HBsAg loss .
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Established And Other Potentially Significant Interactions
Table 4 provides a listing of established or potentially clinically significant drug interactions. The drug interactions described are based on studies conducted with tenofovir alafenamide or are predicted drug interactions that may occur with VEMLIDY . Information regarding potential drug-drug interactions with HIV antiretrovirals is not provided . The table includes potentially significant interactions but is not all inclusive.
| Concomitant Drug Class: Drug Name | Effect on Concentration |
|---|---|
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Tenofovir Disoproxil Fumarate Is Superior To Entecavir In Reducing Hepatitis B Surface Antigen For Chronic Hepatitis B In China: 2
- 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- 2Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- 3Department of Emergency Surgery, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
Aim: Tenofovir disoproxil fumarate and entecavir are equally recommended as the first-line antiviral treatments for chronic hepatitis B at present. We aimed to compare the long-term efficacy and safety between ETV and TDF therapy in CHB patients who had not received nucleoside analog treatment.
Method: In this single-center retrospective study, 414 patients who received ETV or TDF therapy at our center from January 2017 to May 2019 were included. To reduce the imbalance of baseline variables, propensity score matching was employed to yield 124 pairs of patients at a ratio of 1:1 based on the treatment regimen.
TDF has higher potency in reducing HBsAg than ETV in this study. Considering the effect still existed in patients with high HBsAg level , TDF might be a superior therapeutic regimen combining with its relatively safety.
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New Onset Or Worsening Renal Impairment
Tenofovir is principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome , has been reported with the use of VIREAD .
Prior to initiation and during use of VIREAD, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.
Dosing interval adjustment of VIREAD and close monitoring of renal function are recommended in all patients with creatinine clearance below 50 mL/min . No safety or efficacy data are available in patients with renal impairment who received VIREAD using these dosing guidelines, so the potential benefit of VIREAD therapy should be assessed against the potential risk of renal toxicity.
VIREAD should be avoided with concurrent or recent use of a nephrotoxic agent . Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on TDF. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction.
Warning: Posttreatment Acute Exacerbation Of Hepatitis B
Severe acute exacerbations of hepatitis B virus have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including VIREAD. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in HBV-infected patients who discontinue anti-hepatitis B therapy, including VIREAD. If appropriate, resumption of anti-hepatitis B therapy may be warranted .
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