Viread Information
Viread () Indications And Usage
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 () 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:
Viread () Dosage And Administration
For the treatment of HIV-1 or chronic hepatitis B: The dose of Viread () is 300 mg once daily taken orally, without regard to food.
In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown.
Significantly increased drug exposures occurred when Viread () was administered to patients with moderate to severe renal impairment . Therefore, the dosing interval of Viread () should be adjusted in patients with baseline creatinine clearance
No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50–80 mL/min). Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients with mild renal impairment .
The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance
Viread () Dosage Forms And Strengths
Viread () is available as tablets. Each tablet contains 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil. The 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 () Contraindications
Viread () Warnings And Precautions
Discontinuation of anti-HBV therapy, including Viread () , may be associated with severe acute exacerbations of hepatitis. 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.
Tenofovir is principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of Viread () .
It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy and as clinically appropriate during therapy with Viread () . Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients at risk for renal impairment.
Dosing interval adjustment of Viread () and close monitoring of renal function are recommended in all patients with creatinine clearance
Viread () should be avoided with concurrent or recent use of a nephrotoxic agent.
Viread () should not be used in combination with the fixed-dose combination products TRUVADA or ATRIPLA since tenofovir disoproxil fumarate is a component of these products.
Viread () should not be administered in combination with HEPSERA (adefovir dipivoxil)
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 () .
Bone mineral density (BMD) monitoring should be considered for patients who have a history of pathologic bone fracture or are at risk for osteopenia. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected then appropriate consultation should be obtained.
In HIV-infected patients treated with Viread () in Study 903 through 144 weeks, decreases from baseline in BMD were seen at the lumbar spine and hip in both arms of the study. At Week 144, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in patients receiving Viread () + lamivudine + efavirenz (-2.2% ± 3.9) compared with patients receiving stavudine + lamivudine + efavirenz (-1.0% ± 4.6). Changes in BMD at the hip were similar between the two treatment groups (-2.8% ± 3.5 in the Viread () group vs. -2.4% ± 4.5 in the stavudine group). In both groups, the majority of the reduction in BMD occurred in the first 24–48 weeks of the study and this reduction was sustained through Week 144. Twenty-eight percent of Viread () -treated patients vs. 21% of the stavudine-treated patients lost at least 5% of BMD at the spine or 7% of BMD at the hip. Clinically relevant fractures (excluding fingers and toes) were reported in 4 patients in the Viread () group and 6 patients in the stavudine group. In addition, there were significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide, and urinary N-telopeptide) in the Viread () group relative to the stavudine group, suggesting increased bone turnover. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in the Viread () group. Except for bone specific alkaline phosphatase, these changes resulted in values that remained within the normal range. The effects of Viread () -associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown.
Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread () .
The bone effects of Viread () have not been studied in patients with chronic HBV infection.
Clinical studies in HIV-infected patients have demonstrated that certain regimens that only contain three nucleoside reverse transcriptase inhibitors (NRTI) are generally less effective than triple drug regimens containing two NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor or a HIV-1 protease inhibitor. In particular, early virological failure and high rates of resistance substitutions have been reported. Triple nucleoside regimens should therefore be used with caution. Patients on a therapy utilizing a triple nucleoside-only regimen should be carefully monitored and considered for treatment modification.
Viread () Adverse Reactions
The following adverse reactions are discussed in other sections of the labeling:
The following adverse reactions have been identified during postapproval use of Viread () . Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders
Metabolism and Nutrition Disorders
Gastrointestinal Disorders
Hepatobiliary Disorders
Skin and Subcutaneous Tissue Disorders
Musculoskeletal and Connective Tissue Disorders
Renal and Urinary Disorders
General Disorders and Administration Site Conditions
The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.
Viread () Drug Interactions
This section describes clinically relevant drug interactions with Viread () . Drug interactions studies are described elsewhere in the labeling
Coadministration of Viread () and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse reactions. Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions.
When administered with Viread () , C and AUC of didanosine (administered as either the buffered or enteric-coated formulation) increased significantly . The mechanism of this interaction is unknown. Higher didanosine concentrations could potentiate didanosine-associated adverse reactions, including pancreatitis and neuropathy. Suppression of CD4 cell counts has been observed in patients receiving tenofovir disoproxil fumarate (tenofovir DF) with didanosine 400 mg daily.
In adults weighing >60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with Viread () . Data are not available to recommend a dose adjustment of didanosine for patients weighing
Atazanavir has been shown to increase tenofovir concentrations . The mechanism of this interaction is unknown. Patients receiving atazanavir and Viread () should be monitored for Viread () -associated adverse reactions. Viread () should be discontinued in patients who develop Viread () -associated adverse reactions.
Viread () decreases the AUC and Cof atazanavir . When coadministered with Viread () , it is recommended that atazanavir 300 mg is given with ritonavir 100 mg. Atazanavir without ritonavir should not be coadministered with Viread () .
Since tenofovir is primarily eliminated by the kidneys , coadministration of Viread () with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir and/or increase the concentrations of other renally eliminated drugs. Some examples include, but are not limited to cidofovir, acyclovir, valacyclovir, ganciclovir, and valganciclovir. Drugs that decrease renal function may also increase serum concentrations of tenofovir.
In the treatment of chronic hepatitis B, Viread () should not be administered in combination with HEPSERA (adefovir dipivoxil).
Viread () Use In Specific Populations
Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV-1.
mothers should be instructed not to breast-feed if they are receiving Viread () .
Viread () Overdosage
Limited clinical experience at doses higher than the therapeutic dose of Viread () 300 mg is available. In Study 901, 600 mg tenofovir disoproxil fumarate was administered to 8 patients orally for 28 days. No severe adverse reactions were reported. The effects of higher doses are not known.
If overdose occurs the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of Viread () , a four-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.
Viread () Description
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.
The chemical name of tenofovir disoproxil fumarate is 9-[()-2-[[bis[[(isopropoxycarbonyl)oxy]methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of CHNOP • CHO and a molecular weight of 635.52. It has the following structural formula:
Tenofovir disoproxil fumarate is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in distilled water at 25 °C. It has an octanol/phosphate buffer (pH 6.5) partition coefficient (log p) of 1.25 at 25 °C.
Viread () tablets are for oral administration. Each tablet contains 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil, and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. The tablets are coated with Opadry II Y–30–10671–A, which contains FD&C blue #2 aluminum lake, hydroxypropyl methylcellulose 2910, lactose monohydrate, titanium dioxide, and triacetin.
In this insert, all dosages are expressed in terms of tenofovir disoproxil fumarate except where otherwise noted.
Viread () Nonclinical Toxicology
Long-term oral carcinogenicity studies of tenofovir disoproxil fumarate in mice and rats were carried out at exposures up to approximately 16 times (mice) and 5 times (rats) 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.
Tenofovir disoproxil fumarate was mutagenic in the in vitro mouse lymphoma assay and negative in an in vitro bacterial mutagenicity test (Ames test). In an in vivo mouse micronucleus assay, tenofovir disoproxil fumarate was negative when administered to male mice.
There were no effects on fertility, mating performance or early embryonic development when tenofovir disoproxil fumarate 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.
Tenofovir and tenofovir disoproxil fumarate administered in toxicology studies to rats, dogs, and monkeys at exposures (based on AUCs) greater than or equal to 6 fold those observed in humans caused bone toxicity. In monkeys the bone toxicity was diagnosed as osteomalacia. Osteomalacia observed in monkeys appeared to be reversible upon dose reduction or discontinuation of tenofovir. In rats and dogs, the bone toxicity manifested as reduced bone mineral density. The mechanism(s) underlying bone toxicity is unknown.
Evidence of renal toxicity was noted in 4 animal species. Increases in serum creatinine, BUN, glycosuria, proteinuria, phosphaturia, and/or calciuria and decreases in serum phosphate were observed to varying degrees in these animals. These toxicities were noted at exposures (based on AUCs) 2–20 times higher than those observed in humans. The relationship of the renal abnormalities, particularly the phosphaturia, to the bone toxicity is not known.
Viread () How Supplied/storage And Handling
The almond-shaped, light blue, film-coated tablets contain 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil, are debossed with "GILEAD" and "4331" on one side and with "300" on the other side, and are available in unit of use bottles (containing a desiccant [silica gel canister or sachet] and closed with a child-resistant closure) of:
Viread () Patient Counseling Information
Viread ()
Viread ()
Viread () Principal Display Panel - Pouch
Viread ()
(tenofovir disoproxil fumarate) Tablet
300 mg
Viread ()
