Truvada Information
Truvada () Indications And Usage
The following points should be considered when initiating therapy with Truvada () for the treatment of HIV-1 infection:
Truvada () Dosage And Administration
The dose of Truvada () for adults and pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg (greater than or equal to 77 lb) is one tablet (containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) once daily taken orally with or without food.
Significantly increased drug exposures occurred when EMTRIVA or VIREAD were administered to subjects with moderate to severe renal impairment . Therefore, the dosing interval of Truvada () should be adjusted in patients with baseline creatinine clearance 30–49 mL/min using the recommendations in Table 1. These dosing interval recommendations are based on modeling of single-dose pharmacokinetic data in non-HIV infected subjects. The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated in patients with moderate renal impairment, therefore clinical response to treatment and renal function should be closely monitored in these patients .
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.
No data are available to make dose recommendations in pediatric patients 12 years of age and older with renal impairment.
Truvada () Dosage Forms And Strengths
Truvada () is available as tablets. Each tablet contains 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil). The tablets are blue, capsule-shaped, film-coated, debossed with "GILEAD" on one side and with "701" on the other side.
Truvada () Contraindications
Truvada () Warnings And Precautions
Emtricitabine and tenofovir are 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 Truvada () . Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving HEPSERA.
Dosing interval adjustment of Truvada () and close monitoring of renal function are recommended in all patients with creatinine clearance 30–49 mL/min, . No safety or efficacy data are available in patients with renal impairment who received Truvada () using these dosing guidelines, so the potential benefit of Truvada () therapy should be assessed against the potential risk of renal toxicity. Truvada () should not be administered to patients with creatinine clearance below 30 mL/min or patients requiring hemodialysis.
Truvada () should be avoided with concurrent or recent use of a nephrotoxic agent.
Truvada () is a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate. Truvada () should not be coadministered with ATRIPLA, EMTRIVA, or VIREAD. Due to similarities between emtricitabine and lamivudine, Truvada () should not be coadministered with other drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine).
Truvada () should not be administered with HEPSERA (adefovir dipivoxil)
Assessment of bone mineral density (BMD) should be considered for HIV-1 infected adults and pediatric patients 12 years of age and older who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. 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.
Truvada () 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. No additional adverse reactions have been identified during postapproval use of EMTRIVA. 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.
Truvada () Drug Interactions
No drug interaction trials have been conducted using Truvada () tablets. Drug interaction trials have been conducted with emtricitabine and tenofovir disoproxil fumarate, the components of Truvada () . This section describes clinically relevant drug interactions observed with emtricitabine and tenofovir disoproxil fumarate .
Coadministration of Truvada () 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 tenofovir disoproxil fumarate was administered with didanosine the 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 DF with didanosine 400 mg daily.
In patients weighing greater than 60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with Truvada () . Data are not available to recommend a dose adjustment of didanosine for adult or pediatric patients weighing less than 60 kg. When coadministered, Truvada () and Videx EC may be taken under fasted conditions or with a light meal (less than 400 kcal, 20% fat). Coadministration of didanosine buffered tablet formulation with Truvada () should be under fasted conditions.
Atazanavir has been shown to increase tenofovir concentrations . The mechanism of this interaction is unknown. Patients receiving atazanavir and Truvada () should be monitored for Truvada () -associated adverse reactions. Truvada () should be discontinued in patients who develop Truvada () -associated adverse reactions
Tenofovir decreases the AUC and Cof atazanavir . When coadministered with Truvada () , it is recommended that atazanavir 300 mg is given with ritonavir 100 mg. Atazanavir without ritonavir should not be coadministered with Truvada ()
Truvada () 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 Truvada ()
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Truvada () Overdosage
If overdose occurs the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
Emtricitabine:
Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.
Tenofovir Disoproxil Fumarate:
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.
Truvada () Description
Truvada () tablets are fixed dose combination tablets containing emtricitabine and tenofovir disoproxil fumarate. EMTRIVA is the brand name for emtricitabine, a synthetic nucleoside analog of cytidine. Tenofovir disoproxil fumarate (tenofovir DF) is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Both emtricitabine and tenofovir exhibit inhibitory activity against HIV-1 reverse transcriptase.
It has a molecular formula of CHFNOS and a molecular weight of 247.24. It has the following structural formula:
Emtricitabine is a white to off-white crystalline powder with a solubility of approximately 112 mg/mL in water at 25 °C. The partition coefficient (log p) for emtricitabine is -0.43 and the pKa is 2.65.
Tenofovir disoproxil fumarate is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in water at 25 °C. The partition coefficient (log p) for tenofovir disoproxil is 1.25 and the pKa is 3.75. All dosages are expressed in terms of tenofovir disoproxil fumarate except where otherwise noted.
Truvada () Clinical Pharmacology
For additional information on Mechanism of Action, Antiviral Activity, Resistance and Cross Resistance, please consult the EMTRIVA and VIREAD prescribing information.
Truvada () Nonclinical Toxicology
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.
Truvada () Clinical Studies
Clinical Study 934 supports the use of Truvada () tablets for the treatment of HIV-1 infection. Additional data in support of the use of Truvada () are derived from Study 903, in which lamivudine and tenofovir disoproxil fumarate (tenofovir DF) were used in combination in treatment-naive adults, and clinical Study 303 in which emtricitabine and lamivudine demonstrated comparable efficacy, safety and resistance patterns as part of multidrug regimens. For additional information about these trials, please consult the prescribing information for tenofovir DF and emtricitabine.
Truvada () How Supplied/storage And Handling
The blue, capsule-shaped, film-coated, tablets contain 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil), are debossed with "GILEAD" on one side and with "701" on the other side, and are available in unit of use bottles (containing a dessicant [silica gel canister or sachet] and closed with a child-resistant closure) of:
Truvada ()
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