WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including VIREAD, in combination with other antiretrovirals [See Warnings and Precautions].
Severe acute exacerbations of hepatitis 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 patients who discontinue anti-hepatitis B therapy, including VIREAD. If appropriate, resumption of anti-hepatitis B therapy may be warranted [See Warnings and Precautions].
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VIREAD SUMMARY
VIREAD is the brand name for tenofovir disoproxil fumarate (a prodrug of tenofovir) which is a fumaric acid salt of bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir. In vivo tenofovir disoproxil fumarate is converted to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Tenofovir exhibits activity against HIV-1 reverse transcriptase.
HIV-1 Infection
VIREAD® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
The following points should be considered when initiating therapy with VIREAD for the treatment of HIV-1 infection:
- VIREAD should not be used in combination with TRUVADA® or ATRIPLA® [ See Warnings and Precautions
].
Chronic Hepatitis B
VIREAD is indicated for the treatment of chronic hepatitis B in adults.
The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:
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This indication is based on data from one year of treatment in primarily nucleoside-treatment-naïve adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease [See Clinical Efficacy in Patients with Chronic Hepatitis B].
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The numbers of patients in clinical trials who were nucleoside-experienced or who had lamivudine-associated mutations at baseline were too small to reach conclusions of efficacy [See Clinical Efficacy in Patients with Chronic Hepatitis B].
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VIREAD has not been evaluated in patients with decompensated liver disease.
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NEWS HIGHLIGHTSMedia Articles Related to Viread (Tenofovir Disoproxil)
Higher-Dose, Once-Daily Raltegravir Regimen for HIV-1
Source: Medscape HIV/AIDS Headlines [2017.09.26]
A 1,200-mg, once-daily regimen of raltegravir, in combination with tenofovir disoproxil fumarate and emtricitabine, is effective in patients with previously untreated HIV-1 infection, according to results from the ONCEMRK trial.
Reuters Health Information
Published Studies Related to Viread (Tenofovir Disoproxil)
Viral suppression and cirrhosis regression with tenofovir disoproxil fumarate in
Asians with chronic hepatitis B. [2015]
(TDF) in Asian patients through 240 weeks of treatment... CONCLUSIONS: Long-term virologic and histologic efficacy and safety of TDF are
Single-agent tenofovir versus combination emtricitabine plus tenofovir for
pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a
randomised, double-blind, phase 3 trial. [2014]
as PrEP... INTERPRETATION: These results do not rule out the potential for a slight
Association of higher plasma vitamin D binding protein and lower free calcitriol
levels with tenofovir disoproxil fumarate use and plasma and intracellular
tenofovir pharmacokinetics: cause of a functional vitamin D deficiency? [2013]
Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by
an unknown mechanism(s)... Separate pharmacokinetic properties may be
associated with distinct TDF toxicities: tenofovir with parathyroid hormone and
altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23
regulation.
Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok,
Thailand (the Bangkok Tenofovir Study): a randomised, double-blind,
placebo-controlled phase 3 trial. [2013]
users... INTERPRETATION: In this study, daily oral tenofovir reduced the risk of HIV
Sexual risk behavior among HIV-uninfected men who have sex with men participating
in a tenofovir preexposure prophylaxis randomized trial in the United States. [2013]
enrollment or after a 9-month delay and followed for 24 months... CONCLUSIONS: There was no evidence of risk compensation among HIV-uninfected MSM
Clinical Trials Related to Viread (Tenofovir Disoproxil)
Comparison of Tenofovir Vaginal Gel and Film Formulations [Recruiting]
This is an open label comparative study of tenofovir gel and film in 10 healthy sexually
active women without active female genital tract disorders. The women will receive a single
dose of each formulation - tenofovir gel (1%;equivalent to 40 mg in 4ml's of gel) and
tenofovir film (1. 3%;40 mg) - in a crossover study design to determine the pharmacokinetics
of tenofovir in the blood, cervical tissue, and cervicovaginal fluid (primary objective).
A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B [Completed]
Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Negative Hepatitis B [Recruiting]
The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide
(TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and
experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by
the achievement of HBV DNA < 29 IU/mL at Week 48.
Optimal Time for Tenofovir Treatment of Anti-Hepatitis B Virus (HBV) During the Pregnancy [Not yet recruiting]
To determine the optimal time for the Tenofovir treatment of anti-Hepatitis B Virus (HBV)
during the pregnancy among women with chronic HBV infection and high HBV DNA load. This is a
randomized, open-label, three-arms, parallel-controlled clinical trial. Pregnant women with
high HBV load and normal liver function will be treated with tenofovir during the middle or
late stage of pregnancy, started from 24th gestational week, 28th gestational week and 32th
gestational week through 1 month postpartum, respectively. The HBV DNA load at 40th
gestational week of mothers, the intrauterine HBV infection rate of infants will be compared
across the three groups.
Tenofovir vs. Tenofovir Plus Entecavir in Entecavir-Resistant Chronic Hepatitis B [Active, not recruiting]
With the availability of potent nucloes(t)ide analogues (NA), such as tenofovir disoproxil
fumarate (TDF) and entecavir (ETV), suppression of serum HBV DNA to undetectable levels by
polymerase chain reaction (PCR) assays became achievable in most NA treatment-naïve
patients. Until recently, however, many patients commenced antiviral treatment with inferior
NAs prior to the availability of TDF or ETV, such as lamivudine (LAM) which has a low
genetic barrier to resistance.
ETV resistance increase up to 51% of patients after 5 years of ETV treatment in
lamivudine-refractory patients. Resistance to ETV appears to occur through a two-hit
mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at
rtT184, rtS202, or rtM250.
In vitro studies showed that ETV-resistant mutations are susceptible to TDF, but there are
little clinical data on the efficacy of TDF monotherapy in patients with ETV-resistance.
On the other hand, there was a retrospective cohort study reporting that, with the
combination of TDF and ETV, most of patients became HBV DNA undetectable after median 6
months of treatment. Probability of reaching complete HBV DNA suppression was not decreased
in patients with ADV or ETV-resistance.
Thus, there is no consistent treatment recommendation for patients with ETV-resistance.
In this clinical trial, the investigators will clarify whether tenofovir monotherapy is as
effective as tenofovir plus entecavir in inducing complete virologic response in CHB
patients with genotypic resistance to ETV and partial virologic response to ongoing
treatment.
Reports of Suspected Viread (Tenofovir Disoproxil) Side Effects
Renal Failure Acute (19),
Viral Load Increased (16),
Renal Failure (15),
Lactic Acidosis (14),
Fanconi Syndrome (13),
Maternal Exposure During Pregnancy (13),
Renal Impairment (12),
Drug Ineffective (10),
Abortion Spontaneous (9),
Death (9), more >>
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Page last updated: 2017-09-26
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