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U.S. Department of Health and Human Services

Safety

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Tenofovir October 2013 Labeling Updates

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

  • Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) Tablets 
  • Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) Tablets
  • Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) fixed dose combination tablets
  • Truvada (emtricitabine/tenofovir disoproxil fumarate) tablets
  • Viread (tenofovir disoproxil fumarate) tablets and oral powder

 

October 2013

Summary View

WARNINGS AND PRECAUTIONS

New Onset or Worsening Renal Impairment
  • It is recommended that estimated creatinine clearance be assessed in all patients prior to initiating therapy and as clinically appropriate during therapy with Viread/Stribild/Truvada/Complera/Atripla. In patients at risk of renal dysfunction, including patients who have previously experienced renal events while receiving Hespera, it is recommended that estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein be assessed prior to initiation of Viread/Stribild/Truvada/Complera/Atripla , and periodically during  Viread/Stribild/Truvada/Complera/Atripla  therapy.
  • Viread/Stribild/Truvada/Complera/Atripla should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs)). 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…
Bone Effects of Tenofovir DF

Bone Mineral Density:

  • In clinical trials in HIV-1 infected adults, Viread/Stribild/Truvada/Complera/Atripla  was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving Viread/Stribild/Truvada/Complera/Atripla.
  • Clinical trials evaluating Viread in pediatric and adolescent subjects were conducted. Under normal circumstances, BMD increases rapidly in pediatric…

Mineralization Defects:

  • Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of Viread/Stribild/Truvada/Complera/Atripla . Arthralgias and muscle pain or weakness have also been reported in cases of proximal renal tubulopathy. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving products containing tenofovir DF.

ADVERSE REACTIONS

Adverse Reactions from Clinical Trials Experience

Changes in Bone Mineral Density:

  • Clinical trials in HIV-1 infected children and adolescents evaluated BMD changes. In Study 321 (12 to less than 18 years), the mean rate of BMD gain at Week 48 was less in the Viread/Stribild/Truvada/Complera/Atripla  compared to the placebo treatment group…

Changes in Bone Mineral Density:

  • In clinical trials of HIV-1 uninfected individuals, decreases in BMD were observed. In the iPrEx trial, a substudy of 503 subjects found mean changes from baseline in BMD ranging from -0.4% to -1.0% across total hip, spine, femoral neck, and trochanter in the TRUVADA group compared with the placebo group, which returned toward...

DRUG INTERACTIONS

HIV-1 Protease Inhibitors
  • Viread/Stribild/Truvada/Complera/Atripla decreases the AUC and Cmin of atazanavir. When coadministered with Viread/Stribild/Truvada, it is recommended that atazanavir 300 mg is given with ritonavir 100 mg. Viread/Stribild/Truvada should not be coadministered with atazanavir without ritonavir.
  • Lopinavir/ritonavir, atazanavir coadministered with ritonavir, and darunavir coadministered with ritonavir have been shown to increase tenofovir concentrations. Tenofovir disoproxil fumarate is a substrate of Pglycoprotein (Pgp) and breast cancer resistance protein (BCRP) transporters. When tenofovir disoproxil fumarate is co-administered with an inhibitor of these transporters, an increase in absorption may be observed. Patients receiving Viread/Stribild/Truvada concomitantly with lopinavir/ritonavir, ritonavir-boosted atazanavir, or ritonavir-boosted darunavir should be monitored for Viread/Stribild/Truvada -associated adverse reactions. Viread/Stribild/Truvada should be discontinued in patients who develop Viread/Stribild/Truvada -associated adverse reactions.
Drugs Affecting Renal Function
  • Emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion. No drug-drug interactions due to competition for renal excretion have been observed; however, coadministration of Viread/Stribild/Truvada/Complera/Atripla  with drugs that are eliminated by active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the coadministered drug. Some examples include, but are not limited to acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs. Drugs that decrease renal function may increase concentrations of emtricitabine and/or tenofovir.