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The following adverse reactions are discussed in other sections of the labeling:

• Lactic Acidosis/Severe Hepatomegaly with Steatosis [See BOXED WARNING, WARNINGS AND PRECAUTIONS].
• Severe Acute Exacerbations of hepatitis B [See BOXED WARNING, WARNINGS AND PRECAUTIONS].
• New Onset or Worsening Renal Impairment [See WARNINGS AND PRECAUTIONS].
• Decreases in Bone Mineral Density [See WARNINGS AND PRECAUTIONS].
• Immune Reconstitution Syndrome [See WARNINGS AND PRECAUTIONS].

Adverse Reactions from Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials in Adult Subjects

The most common adverse reactions (incidence greater than or equal to 10%, any severity) occurring in Study 934, an active-controlled clinical trial of efavirenz, emtricitabine, and tenofovir disoproxil fumarate, include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. See also Table 2 for the frequency of treatment-emergent adverse reactions (Grade 2–4) occurring in greater than or equal to 5% of subjects treated with efavirenz, emtricitabine, and tenofovir disoproxil fumarate in this trial.

Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Study 934 - Treatment Emergent Adverse Reactions

In Study 934, 511 antiretroviralnaive subjects received either VIREAD + EMTRIVA administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this trial were generally consistent with those seen in other trials in treatment-experienced or treatment-naive subjects receiving VIREAD and/or EMTRIVA (Table 2).

Table 2 : Selected Treatment-Emergent Adverse Reactions^a (Grades 2–4) Reported in ≥ 5% in Any Treatment Group in Study 934 (0–144 Weeks)

Laboratory Abnormalities

Laboratory abnormalities observed in this trial were generally consistent with those seen in other trials of VIREAD and/or EMTRIVA (Table 3).

Table 3 : Significant Laboratory Abnormalities Reported in ≥ 1% of Subjects in Any Treatment Group in Study 934 (0–144 Weeks)

In addition to the events described above for Study 934, other adverse reactions that occurred in at least 5% of subjects receiving EMTRIVA or VIREAD with other antiretroviral agents in clinical trials include anxiety, arthralgia, increased cough, dyspepsia, fever, myalgia, pain, abdominal pain, back pain, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), pneumonia, and rhinitis.

In addition to the laboratory abnormalities described above for Study 934, Grade 3/4 laboratory abnormalities of increased bilirubin ( > 2.5 x ULN), increased pancreatic amylase ( > 2.0 x ULN), increased or decreased serum glucose ( < 40 or > 250 mg/dL), and increased serum lipase ( > 2.0 x ULN) occurred in up to 3% of subjects treated with EMTRIVA or VIREAD with other antiretroviral agents in clinical trials.

Clinical Trials in Pediatric Subjects 12 Years of Age and Older

Emtricitabine: In addition to the adverse reactions reported in adults, anemia and hyperpigmentation were observed in 7% and 32%, respectively, of pediatric subjects (3 months to less than 18 years of age) who received treatment with EMTRIVA in the larger of two open-label, uncontrolled pediatric trials (N=116). For additional information, please consult the EMTRIVA prescribing information.

Tenofovir Disoproxil Fumarate: In a pediatric clinical trial conducted in subjects 12 to less than 18 years of age, the adverse reactions observed in pediatric subjects who received treatment with VIREAD were consistent with those observed in clinical trials of VIREAD in adults [See WARNINGS AND PRECAUTIONS].

Postmarketing Experience

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

allergic reaction, including angioedema

Metabolism and Nutrition Disorders

lactic acidosis, hypokalemia, hypophosphatemia

Respiratory, Thoracic, and Mediastinal Disorders

dyspnea

Gastrointestinal Disorders

pancreatitis, increased amylase, abdominal pain

Hepatobiliary Disorders

hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)

Skin and Subcutaneous Tissue Disorders

rash

Musculoskeletal and Connective Tissue Disorders

rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy

Renal and Urinary Disorders

acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

General Disorders and Administration Site Conditions

asthenia

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.

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 [See CLINICAL PHARMACOLOGY].

Didanosine

Coadministration of TRUVADA and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosineassociated adverse reactions. Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions.

When tenofovir disoproxil fumarate was administered with didanosine the Cmax and AUC of didanosine administered as either the buffered or enteric-coated formulation increased significantly [See CLINICAL PHARMACOLOGY]. The mechanism of this interaction is unknown. Higher didanosine concentrations could potentiate didanosineassociated 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

Atazanavir has been shown to increase tenofovir concentrations [See CLINICAL PHARMACOLOGY]. 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 Cmin of atazanavir [See CLINICAL PHARMACOLOGY]. 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.

Lopinavir/Ritonavir

Lopinavir/ritonavir has been shown to increase tenofovir concentrations [See CLINICAL PHARMACOLOGY]. The mechanism of this interaction is unknown. Patients receiving lopinavir/ritonavir and TRUVADA should be monitored for TRUVADA-associated adverse reactions. TRUVADA should be discontinued in patients who develop 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 [See CLINICAL PHARMACOLOGY]. No drug-drug interactions due to competition for renal excretion have been observed; however, coadministration of TRUVADA 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, and valganciclovir. Drugs that decrease renal function may increase concentrations of emtricitabine and/or tenofovir.

Last reviewed on RxList: 8/2/2011
This monograph has been modified to include the generic and brand name in many instances.