INDICATION

ATRIPLA is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients at least 12 years of age and weighing ≥40 kg (88 lbs).

SELECTED IMPORTANT SAFETY INFORMATION

WARNING: POSTTREATMENT EXACERBATION OF HEPATITIS B

ATRIPLA is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of ATRIPLA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA® (emtricitabine) or VIREAD® (tenofovir DF), which are components of ATRIPLA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue ATRIPLA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

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ATRIPLA—once-daily single-tablet dosing1

Recommended dosage of ATRIPLA

Indication:
ATRIPLA® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate [DF] 300 mg) is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients at least 12 years of age and weighing ≥40 kg (88 lbs).

ATRIPLA dosing and administration ATRIPLA dosing and administration

Renal impairment

Because ATRIPLA is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment, such as those with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min).1

Rifampin coadministration

When ATRIPLA is administered with rifampin to patients weighing 50 kg (110 lbs) or more, an additional 200 mg/day of efavirenz is recommended.1

Contraindications

  • Hypersensitivity to efavirenz: ATRIPLA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of ATRIPLA.
  • Voriconazole: ATRIPLA should not be administered concurrently with voriconazole. Efavirenz, a component of ATRIPLA, significantly decreases voriconazole plasma concentrations, which may decrease voriconazole efficacy. Voriconazole significantly increases efavirenz plasma concentrations, which may increase the risk of efavirenz-associated side effects.

ATRIPLA 3-YEAR SAFETY DATA

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Reference: 1. ATRIPLA [package insert]. Foster City, CA: Bristol-Myers Squibb Company & Gilead Sciences, LLC.

More Important Safety Information 

IMPORTANT SAFETY INFORMATION

WARNING: POSTTREATMENT EXACERBATION OF HEPATITIS B

ATRIPLA is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of ATRIPLA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B
have been reported in patients
who have discontinued
EMTRIVA® (emtricitabine) or
VIREAD® (tenofovir DF), which are components of ATRIPLA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue ATRIPLA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Contraindications

  • ATRIPLA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of ATRIPLA.
  • ATRIPLA should not be administered concurrently with voriconazole. Efavirenz, a component of ATRIPLA, significantly decreases voriconazole plasma concentrations, which may decrease voriconazole efficacy. Voriconazole significantly increases efavirenz plasma concentrations, which may increase the risk of efavirenz-associated side effects.

Warnings and Precautions

  • Efavirenz plasma concentrations may be altered by substrates, inhibitors, or inducers of CYP3A. Efavirenz may alter plasma concentrations of drugs metabolized by CYP3A or CYP2B6. The most prominent effect of efavirenz at steady state is induction of CYP3A and CYP2B6.
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir DF and emtricitabine, components of ATRIPLA, alone or in combination with other antiretrovirals. Suspend treatment with ATRIPLA in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
  • ATRIPLA is a fixed-dose combination of efavirenz, emtricitabine, and tenofovir DF. Do not coadminister ATRIPLA with COMPLERA® (emtricitabine/rilpivirine/
    tenofovir DF), DESCOVY® (emtricitabine
    /tenofovir alafenamide),
    EMTRIVA® (emtricitabine),
    GENVOYA® (elvitegravir/cobicistat
    /emtricitabine/tenofovir alafenamide),
    ODEFSEY® (emtricitabine/rilpivirine/
    tenofovir alafenamide),
    STRIBILD® (elvitegravir/cobicistat/
    emtricitabine/tenofovir DF), TRUVADA® (emtricitabine/tenofovir DF), VEMLIDY® (tenofovir alafenamide), or VIREAD® (tenofovir DF). ATRIPLA should not be coadministered with SUSTIVA® (efavirenz) unless needed for dose-adjustment (e.g., with rifampin). Due to similarities between emtricitabine and lamivudine, ATRIPLA should not be coadministered with drugs containing lamivudine, including
    Combivir® (lamivudine/zidovudine),
    Epivir® or Epivir-HBV® (lamivudine),
    Epzicom® (abacavir sulfate/lamivudine),
    or Trizivir® (abacavir sulfate
    /lamivudine/zidovudine).
  • QTc prolongation has been observed with efavirenz. Consider alternatives to ATRIPLA when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes.
  • ATRIPLA should not be administered with HEPSERA® (adefovir dipivoxil).
  • Serious psychiatric adverse experiences, including severe depression (2.4%, 0.9%), suicidal ideation (0.7%, 0.3%),
    nonfatal suicide attempts (0.5%, 0%), aggressive behavior (0.4%, 0.5%), paranoid reactions (0.4%, 0.3%), and
    manic reactions (0.2%, 0.3%), have been reported in patients receiving efavirenz (N=1,008) and control (N=635) regimens, respectively. In addition to efavirenz, factors identified in a clinical trial that were associated with an increase in psychiatric symptoms included history of injection drug use, psychiatric history, and use of psychiatric medication. There have been occasional reports of suicide, delusions, psychosis-like behavior, and catatonia, but it could not be determined if efavirenz was the cause. Patients with serious psychiatric adverse experiences should be evaluated immediately to determine whether the risks of continued therapy outweigh the benefits.
  • Fifty-three percent of patients (N=1,008) reported central nervous system (CNS) symptoms (including dizziness [28.1%], insomnia [16.3%], impaired concentration [8.3%], somnolence [7.0%],
    abnormal dreams [6.2%], and
    hallucinations [1.2%]) when taking efavirenz compared to 25% of patients (N=635) receiving control regimens. These symptoms usually begin during Days 1-2 of therapy and generally resolve after the first 2-4 weeks of therapy; they were severe in 2.0% of patients, mild to moderate in 50.7% of patients, and 2.1% of patients discontinued therapy. After 4 weeks of therapy, the prevalence of CNS symptoms of at least moderate severity ranged from 5% to 9% in patients treated with regimens containing efavirenz. Nervous system symptoms are not predictive of the less frequent psychiatric symptoms. Patients receiving ATRIPLA should be alerted to the potential for additive CNS effects when ATRIPLA is used concomitantly with alcohol or psychoactive drugs. Patients who experience CNS symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.
  • Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia) has been reported with the use of tenofovir DF. ATRIPLA should not be given to patients with estimated creatinine clearance (CrCl) <50 mL/min. It is recommended that estimated CrCl be assessed in all patients prior to initiating therapy and as clinically appropriate. Estimated CrCl, serum phosphorus, urine glucose, and urine protein should be assessed for patients at risk of renal dysfunction prior to initiation and periodically during therapy, including patients who have previously experienced renal events while receiving adefovir dipivoxil.
    • ATRIPLA should be avoided with concurrent or recent use of a nephrotoxic agent (e.g. high-dose and/or multiple non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs, some requiring hospitalization and renal replacement therapy, have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir DF; consider alternatives to NSAIDs in these patients. Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function.
  • ATRIPLA may cause fetal harm when administered during the first trimester to a pregnant woman. Women should not become pregnant or breastfeed while taking ATRIPLA. Barrier contraception must always be used in combination with other methods of contraception (e.g., oral or other hormonal contraceptives). Because of the long half-life of efavirenz, adequate contraceptive measures are recommended for 12 weeks after discontinuation of ATRIPLA. If the patient becomes pregnant while taking ATRIPLA, she should be apprised of the potential harm to the fetus. Efavirenz, emtricitabine, and tenofovir have been detected in human milk. Mothers should be instructed not to breastfeed because the risks of exposure to these products to the infant are unknown, and because of the potential risks of HIV-1 transmission.
  • Mild-to-moderate rash is a common side effect of efavirenz. In controlled clinical trials in adults, 26% of patients (N=1,008) treated with efavirenz experienced new-onset skin rash compared with 17% of patients (N=635) treated in control groups. ATRIPLA should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. For patients who have had a life-threatening cutaneous reaction (e.g., Stevens-Johnson syndrome), alternative therapy should be considered.
    • Rash was reported in 32% (N=182) of pediatric patients receiving efavirenz. Grade 3 or 4 rash was reported in 3% of pediatric patients compared to 0.9% of adults receiving efavirenz. Consider antihistamine prophylaxis before initiating ATRIPLA in pediatric patients.
  • Liver enzymes should be monitored before and during treatment in patients with underlying hepatic disease, including hepatitis B or C infection; in patients with marked transaminase elevations; and when ATRIPLA is administered with ritonavir or other medications associated with liver toxicity. A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing in some cases to transplantation or death. Liver enzyme monitoring should be considered for patients without pre-existing hepatic dysfunction or other risk factors. The benefit of continued ATRIPLA should be weighed against unknown risks of significant liver toxicity in patients with persistent elevations of serum transaminases >5 times the upper limit of normal.
  • Bone mineral density (BMD) assessment should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Slightly greater decreases in BMD and increases in biochemical markers of bone metabolism have been seen with tenofovir DF in clinical trials in HIV-1 infected adults, suggesting increased bone turnover vs. comparators.
  • Bone 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 tenofovir DF. 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.
  • Use ATRIPLA with caution in patients with a history of seizures. Convulsions have been observed in adult and pediatric patients receiving efavirenz, generally in the presence of known medical history of seizures. Monitor plasma levels of coadministered anticonvulsants metabolized by the liver.
  • Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of ATRIPLA. Autoimmune disorders (e.g., Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
  • Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy, including efavirenz.

Adverse Reactions

  • In Study 934, through 144 weeks,
    the most frequently reported
    Grades 2-4 adverse reactions in ≥5% of subjects receiving efavirenz + emtricitabine + tenofovir DF were diarrhea (9%), nausea (9%),
    fatigue (9%), depression (9%),
    dizziness (8%), sinusitis (8%),
    upper respiratory tract infection (8%), rash event (7%), headache (6%),
    insomnia (5%), anxiety (5%),
    and nasopharyngitis (5%).
  • The most common adverse reactions (incidence ≥10%, any severity) occurring in Study 934 include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.
  • Skin discoloration, associated with emtricitabine, may also occur.
  • Pediatric patients: A higher incidence of rash was reported in pediatric patients (32%) compared to adults (26%). In addition to common adverse events reported in adults, anemia (7%) and hyperpigmentation (32%) were observed in pediatric patients treated with emtricitabine.

Drug Interactions

  • Coadministration of ATRIPLA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine and tenofovir, and/or other renally eliminated drugs.
  • Coadministration of ATRIPLA with didanosine should be undertaken with caution. Patients receiving this combination should be monitored closely for didanosine-associated adverse reactions including pancreatitis, lactic acidosis, and neuropathy. Dose reduction of didanosine is recommended when coadministered with tenofovir DF. Discontinue didanosine in patients who develop didanosine-associated adverse reactions.
  • Coadministration of ATRIPLA with either darunavir and ritonavir or lopinavir/ritonavir increases tenofovir concentrations. These patients should be monitored for tenofovir-associated adverse reactions. Do not use once daily lopinavir/ritonavir with ATRIPLA. Dose increase of lopinavir/ritonavir is recommended when coadministered with efavirenz. Discontinue ATRIPLA in patients who develop tenofovir-associated adverse reactions.
  • Coadministration of ATRIPLA and atazanavir is not recommended. Efavirenz and tenofovir DF have been shown to decrease concentrations of atazanavir. Atazanavir has also been shown to increase tenofovir concentrations.
  • ATRIPLA should not be coadministered with other NNRTIs since combining 2 NNRTIs has not been shown to be beneficial.
  • The combination of ATRIPLA and boceprevir should be avoided. Plasma trough concentrations of boceprevir were decreased when coadministered with efavirenz, which may result in loss of therapeutic effect.
  • The combination of ATRIPLA and simeprevir is not recommended because it may result in loss of therapeutic effect of simeprevir.
  • Coadministration of ATRIPLA and EPCLUSA® (sofosbuvir/velpatasvir) is not recommended.
  • Coadministration of ATRIPLA and atovaquone/proguanil is not recommended.
  • See Full Prescribing Information for complete list of drug-drug interactions.

Hepatic Impairment

ATRIPLA is not recommended for patients with moderate or severe hepatic impairment because of insufficient data; use caution in patients with mild hepatic impairment.

Additional Dosing Considerations

Take ATRIPLA orally on an empty stomach; dosing at bedtime may improve the tolerability of nervous system symptoms. When ATRIPLA is administered with rifampin to patients weighing ≥50 kg, an additional
200 mg/day of efavirenz is recommended.

Please see Full Prescribing Information, for ATRIPLA, including Boxed WARNING.

697US1500695-02-01 08/16

697US1500695-04-01 03/17

More Important Safety Information  

SELECTED IMPORTANT SAFETY INFORMATION

WARNING: POSTTREATMENT EXACERBATION OF HEPATITIS B

ATRIPLA is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of ATRIPLA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA® (emtricitabine) or VIREAD® (tenofovir DF), which are components of ATRIPLA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue ATRIPLA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Contraindications

  • ATRIPLA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of ATRIPLA.
  • ATRIPLA should not be administered concurrently with voriconazole. Efavirenz, a component of ATRIPLA, significantly decreases voriconazole plasma concentrations, which may decrease voriconazole efficacy. Voriconazole significantly increases efavirenz plasma concentrations, which may increase the risk of efavirenz-associated side effects.

Warnings and Precautions

  • Efavirenz plasma concentrations may be altered by substrates, inhibitors, or inducers of CYP3A. Efavirenz may alter plasma concentrations of drugs metabolized by CYP3A or CYP2B6. The most prominent effect of efavirenz at steady state is induction of CYP3A and CYP2B6.
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir DF and emtricitabine, components of ATRIPLA, alone or in combination with other antiretrovirals. Suspend treatment with ATRIPLA in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
  • ATRIPLA is a fixed-dose combination efavirenz, emtricitabine, and tenofovir DF. Do not coadminister ATRIPLA with COMPLERA® (emtricitabine/rilpivirine/tenofovir DF), DESCOVY® (emtricitabine
    /tenofovir alafenamide), EMTRIVA® (emtricitabine), GENVOYA® (elvitegravir/cobicistat/
    emtricitabine/tenofovir alafenamide), ODEFSEY® (emtricitabine/rilpivirine/tenofovir alafenamide), STRIBILD® (elvitegravir/ cobicistat/emtricitabine/tenofovir DF), TRUVADA® (emtricitabine/tenofovir DF), VEMLIDY® (tenofovir alafenamide), or VIREAD® (tenofovir DF). ATRIPLA should not be coadministered with SUSTIVA® (efavirenz) unless needed for dose-adjustment (e.g., with rifampin). Due to similarities between emtricitabine and lamivudine, ATRIPLA should not be coadministered with drugs containing lamivudine, including Combivir® (lamivudine/zidovudine), Epivir® or Epivir-HBV® (lamivudine), Epzicom® (abacavir sulfate/lamivudine), or Trizivir® (abacavir sulfate
    /lamivudine/zidovudine).

Warnings and Precautions

  • ATRIPLA is a fixed-dose combination of efavirenz, emtricitabine, and tenofovir DF. Do not coadminister ATRIPLA with COMPLERA® (emtricitabine/rilpivirine/tenofovir DF), DESCOVY® (emtricitabine/tenofovir alafenamide), EMTRIVA® (emtricitabine), GENVOYA® (elvitegravir/cobicistat
    /emtricitabine/tenofovir alafenamide), ODEFSEY® (emtricitabine/rilpivirine/tenofovir alafenamide), STRIBILD® (elvitegravir/cobicistat/emtricitabine/tenofovir DF), TRUVADA® (emtricitabine/tenofovir DF), VEMLIDY® (tenofovir alafenamide), or VIREAD® (tenofovir DF). ATRIPLA should not be coadministered with SUSTIVA® (efavirenz) unless needed for dose-adjustment (e.g., with rifampin). Due to similarities between emtricitabine and lamivudine, ATRIPLA should not be coadministered with drugs containing lamivudine, including Combivir® (lamivudine/zidovudine), Epivir® or Epivir-HBV® (lamivudine), Epzicom® (abacavir sulfate/lamivudine), or Trizivir® (abacavir sulfate/
    lamivudine/zidovudine).

Warnings and Precautions

  • QTc prolongation has been observed with efavirenz. Consider alternatives to ATRIPLA when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes.
  • ATRIPLA should not be administered with HEPSERA® (adefovir dipivoxil).

Warnings and Precautions

  • In Study 934, through 144 weeks, the most frequently reported Grades 2-4 adverse reactions in ≥5% of subjects receiving efavirenz + emtricitabine + tenofovir DF were diarrhea (9%), nausea (9%), fatigue (9%), depression (9%), dizziness (8%), sinusitis (8%), upper respiratory tract infection (8%), rash event (7%), headache (6%), insomnia (5%), anxiety (5%), and nasopharyngitis (5%).
  • The most common adverse reactions (incidence ≥10%, any severity) occurring in Study 934 include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.
  • Skin discoloration, associated with emtricitabine, may also occur.
  • Pediatric patients: A higher incidence of rash was reported in pediatric patients (32%) compared to adults (26%). In addition to common adverse events reported in adults, anemia (7%) and hyperpigmentation (32%) were observed in pediatric patients treated with emtricitabine.

Warnings and Precautions

  • Serious psychiatric adverse experiences, including severe depression (2.4%, 0.9%), suicidal ideation (0.7%, 0.3%), nonfatal suicide attempts (0.5%, 0%), aggressive behavior (0.4%, 0.5%), paranoid reactions (0.4%, 0.3%), and manic reactions (0.2%, 0.3%), have been reported in patients receiving efavirenz (N=1,008) and control (N=635) regimens, respectively. In addition to efavirenz, factors identified in a clinical trial that were associated with an increase in psychiatric symptoms included history of injection drug use, psychiatric history, and use of psychiatric medication. There have been occasional reports of suicide, delusions, psychosis-like behavior, and catatonia, but it could not be determined if efavirenz was the cause. Patients with serious psychiatric adverse experiences should be evaluated immediately to determine whether the risks of continued therapy outweigh the benefits.

Warnings and Precautions

  • Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia) has been reported with the use of tenofovir DF. ATRIPLA should not be given to patients with estimated creatinine clearance (CrCl) <50 mL/min. It is recommended that estimated CrCl be assessed in all patients prior to initiating therapy and as clinically appropriate. Estimated CrCl, serum phosphorus, urine glucose, and urine protein should be assessed for patients at risk of renal dysfunction prior to initiation and periodically during therapy, including patients who have previously experienced renal events while receiving adefovir dipivoxil.
    • ATRIPLA should be avoided with concurrent or recent use of a nephrotoxic agent (e.g. high-dose and/or multiple non-steroidal anti-inflammatory drugs [NSAIDs]). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs, some requiring hospitalization and renal replacement therapy, have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on tenofovir DF; consider alternatives to NSAIDs in these patients. Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function.

Warnings and Precautions

  • Mild-to-moderate rash is a common side effect of efavirenz. In controlled clinical trials in adults, 26% of patients (N=1,008) treated with efavirenz experienced new-onset skin rash compared with 17% of patients (N=635) treated in control groups. ATRIPLA should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. For patients who have had a life-threatening cutaneous reaction (e.g., Stevens-Johnson syndrome), alternative therapy should be considered.
    • Rash was reported in 32% (N=182) of pediatric patients receiving efavirenz. Grade 3 or 4 rash was reported in 3% of pediatric patients compared to 0.9% of adults receiving efavirenz. Consider antihistamine prophylaxis before initiating ATRIPLA in pediatric patients.
Warnings and Precautions
  • Liver enzymes should be monitored before and during treatment in patients with underlying hepatic disease, including hepatitis B or C infection; in patients with marked transaminase elevations; and when ATRIPLA is administered with ritonavir or other medications associated with liver toxicity. A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing in some cases to transplantation or death. Liver enzyme monitoring should be considered for patients without pre-existing hepatic dysfunction or other risk factors. The benefit of continued ATRIPLA should be weighed against unknown risks of significant liver toxicity in patients with persistent elevations of serum transaminases >5 times the upper limit of normal.

Warnings and Precautions

  • Bone mineral density (BMD) assessment should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Slightly greater decreases in BMD and increases in biochemical markers of bone metabolism have been seen with tenofovir DF in clinical trials in HIV-1 infected adults, suggesting increased bone turnover vs. comparators.
  • Bone 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 tenofovir DF. 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.

Warnings and Precautions

  • ATRIPLA may cause fetal harm when administered during the first trimester to a pregnant woman. Women should not become pregnant or breastfeed while taking ATRIPLA. Barrier contraception must always be used in combination with other methods of contraception (e.g., oral or other hormonal contraceptives). Because of the long half-life of efavirenz, adequate contraceptive measures are recommended for 12 weeks after discontinuation of ATRIPLA. If the patient becomes pregnant while taking ATRIPLA, she should be apprised of the potential harm to the fetus. Efavirenz, emtricitabine, and tenofovir have been detected in human milk. Mothers should be instructed not to breastfeed because the risks of exposure to these products to the infant are unknown, and because of the potential risks of HIV-1 transmission.

Warnings and Precautions

  • Liver enzymes should be monitored before and during treatment in patients with underlying hepatic disease, including hepatitis B or C infection; in patients with marked transaminase elevations; and when ATRIPLA is administered with ritonavir or other medications associated with liver toxicity. A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing in some cases to transplantation or death. Liver enzyme monitoring should be considered for patients without pre-existing hepatic dysfunction or other risk factors. The benefit of continued ATRIPLA should be weighed against unknown risks of significant liver toxicity in patients with persistent elevations of serum transaminases >5 times the upper limit of normal.

WARNING: POSTTREATMENT EXACERBATION OF HEPATITIS B

ATRIPLA is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of ATRIPLA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA® (emtricitabine) or VIREAD® (tenofovir DF), which are components of ATRIPLA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue ATRIPLA. If appropriate, initiation of anti-hepatitis B therapy may be warranted.