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Atripla Side Effects

Please note - some side effects for Atripla may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Atripla - for the Consumer

Atripla

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Atripla:

Back pain; cough; darkened skin color on the palms of hands or soles of feet; diarrhea; dizziness; drowsiness; gas or indigestion; headache; loss of appetite; mild stomach pain; muscle or joint aches; nausea; skin discoloration (small spots or freckles); stomach upset; strange dreams; stuffy or runny nose; tiredness; trouble concentrating; trouble sleeping; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Atripla:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bone pain; change in personality; chest pain; confusion; decreased coordination; delusions; fever, chills, or persistent sore throat; hallucinations; memory loss; mental, mood, or behavior changes (eg, abnormal thoughts, agitation, aggression, anxiety, depression, nervousness, paranoia); muscle pain or weakness; numbness, burning, pain, or tingling of the hands, feet, or skin; red, swollen, blistered, or peeling skin; seizures; severe or persistent stomach pain, nausea, or vomiting; shortness of breath; suicidal thoughts or actions; symptoms of kidney problems (eg, increased or decreased urination, increased thirst); symptoms of lactic acidosis (eg, dizziness or lightheadedness; fast or difficult breathing; fast or irregular heartbeat; feeling cold, especially in the arms and legs; stomach pain with nausea and vomiting; unusual muscle pain; unusual weakness or tiredness); symptoms of liver problems (eg, dark urine; pale stools; persistent loss of appetite; yellowing of the skin or eyes).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Atripla Side Effects - for the Professional

Atripla

Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate: The following adverse reactions are discussed in other sections of the labeling:

For additional safety information about SUSTIVA (efavirenz), EMTRIVA (emtricitabine), or VIREAD (tenofovir DF) in combination with other antiretroviral agents, consult the prescribing information for these products.

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.

Study 934

Study 934 was an open-label active-controlled trial in which 511 antiretroviral-naive subjects received either emtricitabine + tenofovir DF administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254).

The most common adverse reactions (incidence greater than or equal to 10%, any severity) occurring in Study 934 include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. Adverse reactions observed in Study 934 were generally consistent with those seen in previous trials of the individual components (Table 2).

Table 2 Selected Treatment-Emergent Adverse Reactions* (Grades 2–4) Reported in ≥5% in Either Treatment Group in Study 934 (0–144 Weeks)
FTC + TDF + EFV† AZT/3TC + EFV
N=257 N=254
*
Frequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug.
†
From Weeks 96 to 144 of the trial, subjects received emtricitabine/tenofovir DF administered in combination with efavirenz in place of emtricitabine + tenofovir DF with efavirenz.
‡
Rash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular.
Gastrointestinal Disorder
  Diarrhea 9% 5%
  Nausea 9% 7%
  Vomiting 2% 5%
General Disorders and Administration Site Condition
  Fatigue 9% 8%
Infections and Infestations
  Sinusitis 8% 4%
  Upper respiratory tract infections 8% 5%
  Nasopharyngitis 5% 3%
Nervous System Disorders
  Headache 6% 5%
  Dizziness 8% 7%
Psychiatric Disorders
  Anxiety 5% 4%
  Depression 9% 7%
  Insomnia 5% 7%
Skin and Subcutaneous Tissue Disorders
  Rash Event‡ 7% 9%

Study 073

In Study 073, subjects with stable, virologic suppression on antiretroviral therapy and no history of virologic failure were randomized to receive Atripla or to stay on their baseline regimen. The adverse reactions observed in Study 073 were generally consistent with those seen in Study 934 and those seen with the individual components of Atripla when each was administered in combination with other antiretroviral agents.

Efavirenz, Emtricitabine, or Tenofovir Disoproxil Fumarate

In addition to the adverse reactions in Study 934 and Study 073 the following adverse reactions were observed in clinical trials of efavirenz, emtricitabine, or tenofovir DF in combination with other antiretroviral agents.

Efavirenz: The most significant adverse reactions observed in subjects treated with efavirenz are nervous system symptoms [See Warnings and Precautions (5.6)], psychiatric symptoms [See Warnings and Precautions (5.5)], and rash [See Warnings and Precautions (5.9)].

Selected adverse reactions of moderate-severe intensity observed in greater than or equal to 2% of efavirenz-treated subjects in two controlled clinical trials included pain, impaired concentration, abnormal dreams, somnolence, anorexia, dyspepsia, abdominal pain, nervousness, and pruritus.

Pancreatitis has also been reported, although a causal relationship with efavirenz has not been established. Asymptomatic increases in serum amylase levels were observed in a significantly higher number of subjects treated with efavirenz 600 mg than in control subjects.

Emtricitabine and Tenofovir Disoproxil Fumarate: Adverse reactions that occurred in at least 5% of treatment-experienced or treatment-naive subjects receiving emtricitabine or tenofovir DF with other antiretroviral agents in clinical trials include arthralgia, increased cough, dyspepsia, fever, myalgia, pain, abdominal pain, back pain, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), pneumonia, rhinitis and rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash and allergic reaction).

Skin discoloration has been reported with higher frequency among emtricitabine-treated subjects; it was manifested by hyperpigmentation on the palms and/or soles and was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Laboratory Abnormalities

Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate: Laboratory abnormalities observed in Study 934 were generally consistent with those seen in previous trials (Table 3).

Table 3 Significant Laboratory Abnormalities Reported in ≥1% of Subjects in Either Treatment Group in Study 934 (0–144 Weeks)
FTC + TDF + EFV* AZT/3TC + EFV
N=257 N=254
*
From Weeks 96 to 144 of the trial, subjects received emtricitabine/tenofovir DF administered in combination with efavirenz in place of emtricitabine + tenofovir DF with efavirenz.
Any ≥ Grade 3 Laboratory Abnormality 30% 26%
Fasting Cholesterol (>240 mg/dL) 22% 24%
Creatine Kinase
(M: >990 U/L)
(F: >845 U/L)		 9% 7%
Serum Amylase (>175 U/L) 8% 4%
Alkaline Phosphatase (>550 U/L) 1% 0%
AST
(M: >180 U/L)
(F: >170 U/L)		 3% 3%
ALT
(M: >215 U/L)
(F: >170 U/L)		 2% 3%
Hemoglobin (<8.0 mg/dL) 0% 4%
Hyperglycemia (>250 mg/dL) 2% 1%
Hematuria (>75 RBC/HPF) 3% 2%
Glycosuria (≥3+) <1% 1%
Neutrophils (<750/mm3) 3% 5%
Fasting Triglycerides (>750 mg/dL) 4% 2%

Laboratory abnormalities observed in Study 073 were generally consistent with those in Study 934.

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

Hepatic Events: In Study 934, 19 subjects treated with efavirenz, emtricitabine, and tenofovir DF and 20 subjects treated with efavirenz and fixed-dose zidovudine/lamivudine were hepatitis B surface antigen or hepatitis C antibody positive. Among these coinfected subjects, one subject (1/19) in the efavirenz, emtricitabine and tenofovir DF arm had elevations in transaminases to greater than five times ULN through 144 weeks. In the fixed-dose zidovudine/lamivudine arm, two subjects (2/20) had elevations in transaminases to greater than five times ULN through 144 weeks. No HBV and/or HCV coinfected subject discontinued from the trial due to hepatobiliary disorders [See Warnings and Precautions (5.10)].

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of efavirenz, emtricitabine, or tenofovir DF. 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.

Efavirenz:

Cardiac Disorders
Palpitations

Ear and Labyrinth Disorders
Tinnitus, vertigo

Endocrine Disorders
Gynecomastia

Eye Disorders
Abnormal vision

Gastrointestinal Disorders
Constipation, malabsorption

General Disorders and Administration Site Conditions
Asthenia

Hepatobiliary Disorders
Hepatic enzyme increase, hepatic failure, hepatitis. 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.

Immune System Disorders
Allergic reactions

Metabolism and Nutrition Disorders
Redistribution/accumulation of body fat [See Warnings and Precautions (5.14)], hypercholesterolemia, hypertriglyceridemia

Musculoskeletal and Connective Tissue Disorders
Arthralgia, myalgia, myopathy

Nervous System Disorders
Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor

Psychiatric Disorders
Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide

Respiratory, Thoracic and Mediastinal Disorders
Dyspnea

Skin and Subcutaneous Tissue Disorders
Flushing, erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome

Emtricitabine: No postmarketing adverse reactions have been identified for inclusion in this section.

Tenofovir Disoproxil Fumarate:

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.

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Side Effects by Body System - for Healthcare Professionals

General

The most common side effects (any severity; greater than or equal to 10%) reported during a clinical study of efavirenz, emtricitabine, and tenofovir included diarrhea, nausea, headache, fatigue, dizziness, depression, insomnia, abnormal dreams, and rash. The most significant side effects associated with efavirenz are nervous system symptoms, psychiatric symptoms, and rash.

Hepatic

Hepatic side effects have included elevated AST (greater than 180 units/L in males and 170 units/L in females; 3%) and ALT (greater than 215 units/L in males and 170 units/L in females; 2%). Elevated bilirubin (greater than 2.5 times ULN) has been reported in up to 3% of patients treated with emtricitabine or tenofovir. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogs, including tenofovir, in combination with other antiretrovirals. Hepatic enzyme increase, hepatic failure (a few reports were characterized by a fulminant course, with some cases progressing to transplantation or death), and hepatitis have been reported during postmarketing experience with efavirenz. Hepatic steatosis, hepatitis, and increased liver enzymes (primarily AST, ALT, and gamma glutamyl transferase) have been reported during postmarketing experience with tenofovir. Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and hepatitis B after discontinuation of emtricitabine or tenofovir and were associated with liver failure and liver decompensation in some of the emtricitabine-treated patients.

Some of the postmarketing reports of hepatic failure with efavirenz occurred in patients with no preexisting liver disease or other identifiable risk factors.

Gastrointestinal

Gastrointestinal side effects (Grades 2 to 4) have included diarrhea (9%), nausea (9%), and vomiting (2%). Selected side effects of moderate to severe intensity have included anorexia, dyspepsia, and abdominal pain in greater than or equal to 2% of efavirenz-treated patients. Pancreatitis has been reported with efavirenz, although causality was not determined. Dyspepsia and abdominal pain have been reported in at least 5% of patients receiving emtricitabine or tenofovir. Constipation and malabsorption have been reported during postmarketing experience with efavirenz. Pancreatitis, abdominal pain, and increased amylase have been reported during postmarketing experience with tenofovir.

Psychiatric

Psychiatric side effects (Grades 2 to 4) have included depression (9%), anxiety (5%), and insomnia (5%). Selected side effects of moderate to severe intensity have included abnormal dreams and nervousness in greater than or equal to 2% of efavirenz-treated patients. Serious psychiatric side effects associated with efavirenz have included severe depression (2.4%), suicidal ideation (0.7%), nonfatal suicide attempts (0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%), and manic reactions (0.2%). Aggressive reactions, agitation, delusions, emotional lability, mania neurosis, paranoia, psychosis, and suicide have been reported during postmarketing experience with efavirenz.

Dermatologic

Dermatologic side effects (Grades 2 to 4) have included rash event (including rash, exfoliative rash, generalized rash, macular rash, maculopapular rash, pruritic rash, and vesicular rash; 7%). Selected side effects of moderate to severe intensity have included pruritus in greater than or equal to 2% of efavirenz-treated patients. In patients treated with 600 mg of efavirenz during clinical trials, skin rash of any grade (26%) included Grade 1 rash (erythema, pruritus; approximately 10%), Grade 2 rash (diffuse maculopapular rash, dry desquamation;,14.7%), Grade 3 rash (vesiculation, moist desquamation, ulceration; less than 1%), and Grade 4 rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, necrosis requiring surgery, exfoliative dermatitis; 0.1%). Treatment was discontinued in 1.7% of patients due to rash. Nail disorders, skin discoloration, and leukocytoclastic vasculitis have also been reported with efavirenz. Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, and allergic reaction) has been reported in at least 5% of patients receiving emtricitabine or tenofovir. Skin discoloration (palmar-plantar hyperpigmentation) has been reported with emtricitabine. Erythema multiforme, photoallergic dermatitis, and Stevens-Johnson syndrome have been reported during postmarketing experience with efavirenz. Rash has also been reported during postmarketing experience with tenofovir.

Rashes associated with efavirenz are usually mild-to-moderate maculopapular skin eruptions. The median time to onset of rash was 11 days. In most patients, the rash resolved within one month despite continued use of the drug. Patients who discontinue efavirenz therapy because of rash may be reinstated with the use of appropriate antihistamines and/or corticosteroids. The drug should be withdrawn if severe rash develops, such as that associated with blistering, desquamation, mucosal involvement, or fever.

There is limited experience with the use of efavirenz in patients who have previously discontinued other nonnucleoside reverse transcriptase inhibitors (NNRTIs) due to rash. In 19 such patients formerly on nevirapine, approximately half developed a mild to moderate rash, and two of them discontinued efavirenz because of the rash.

Nervous system

Nervous system side effects (Grades 2 to 4) have included dizziness (8%) and headache (6%). Selected side effects of moderate to severe intensity have included impaired concentration and somnolence in greater than or equal to 2% of efavirenz-treated patients. Nervous system symptoms of any grade and regardless of causality (53%) included dizziness (28.1%), insomnia (16.3%), impaired concentration (8.3%), somnolence (7%), abnormal dreams (6.2%), hallucinations (1.2%), amnesia, agitation, euphoria, depersonalization, confusion, abnormal thinking, and stupor during clinical trials of efavirenz in combination with other antiretroviral agents. These symptoms were mild in 33.3%, moderate in 17.4%, and severe in 2% of patients. Therapy was discontinued in 2.1% of patients due to these side effects. Paresthesia and peripheral neuropathy (including peripheral neuritis and neuropathy) have been reported in at least 5% of patients receiving emtricitabine or tenofovir. Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, vertigo, and tinnitus have been reported during postmarketing experience with efavirenz.

Other

Other side effects (Grades 2 to 4) have included fatigue (9%). Pain (moderate to severe intensity; 2% or greater) has been reported with efavirenz. Fever, pain, and back pain have been reported in at least 5% of patients receiving emtricitabine or tenofovir. Asthenia has been reported during postmarketing experience with efavirenz and tenofovir. Contraceptive failure (with an implantable hormonal contraceptive) has been reported during postmarketing experience with efavirenz.

Metabolic

Metabolic side effects have included hyperglycemia (greater than 250 mg/dL; up to 2%), altered serum glucose (less than 40 mg/dL or greater than 250 mg/dL; up to 3%), and elevated fasting cholesterol (greater than 240 mg/dL; up to 22%), creatine kinase (greater than 990 units/L in males and 845 units/L in females; up to 9%), serum amylase (greater than 175 units/L; up to 8%), fasting triglycerides (greater than 750 mg/dL; 4%), and alkaline phosphatase (greater than 550 units/L; 1%). Elevated pancreatic amylase (greater than 2 times ULN; up to 3%) and serum lipase (greater than 2 times ULN; up to 3%) have been reported in up to 3% of patients treated with emtricitabine or tenofovir. Increased body weight has also been reported. Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. Hypercholesterolemia and hypertriglyceridemia have been reported during postmarketing experience with efavirenz. Hypokalemia, lactic acidosis, and hypophosphatemia have been reported during postmarketing experience with tenofovir.

Hypokalemia and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Respiratory

Respiratory side effects (Grades 2 to 4) have included sinusitis (8%), upper respiratory tract infections (8%), and nasopharyngitis (5%). Increased cough, pneumonia, and rhinitis have been reported in at least 5% of patients receiving emtricitabine or tenofovir. Dyspnea has been reported during postmarketing experience with efavirenz and tenofovir.

Renal

Renal side effects have included new onset or worsening renal impairment with tenofovir. Renal insufficiency, renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, acute tubular necrosis, nephrogenic diabetes insipidus, and interstitial nephritis (including acute cases) have been reported during postmarketing experience with tenofovir.

Rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Hematologic

Hematologic side effects have included decreased neutrophils (less than 750/mm3; 3%). Increased hemoglobin has been reported.

Endocrine

Endocrine side effects have included gynecomastia during postmarketing experience with efavirenz.

Cardiovascular

Cardiovascular side effects have included flushing and palpitations during postmarketing experience with efavirenz. QT interval prolongation and torsades de pointes have been reported with efavirenz.

Musculoskeletal

Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy may occur as a result of proximal renal tubulopathy.

Musculoskeletal side effects have included arthralgia and myalgia in at least 5% of patients receiving emtricitabine or tenofovir. Arthralgia, myalgia, and myopathy have been reported during postmarketing experience with efavirenz. Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, and myopathy have been reported during postmarketing experience with tenofovir.

Hypersensitivity

Hypersensitivity side effects have included allergic reactions during postmarketing experience with efavirenz. Allergic reaction (including angioedema) has been reported during postmarketing experience with tenofovir.

Ocular

Ocular side effects have included abnormal vision during postmarketing experience with efavirenz.

Genitourinary

Genitourinary side effects have included hematuria (greater than 75 RBC/HPF; up to 3%) and glycosuria (3 plus or greater; less than 1%). Proteinuria and polyuria have been reported during postmarketing experience with tenofovir.

Immunologic

Immunologic side effects have included immune reconstitution syndrome.

Other

False positive urine drug screening test results for tetrahydrocannabinol and benzodiazepines have been reported in HIV-infected patients receiving efavirenz. False positive cannabinoid test results have been observed with the CEDIA DAU Multilevel THC assay and the InstaCheck multidrug Screen Panel. The Triage 8 and the Drug Screen Multi 5 have shown false-positive results for benzodiazepines and tetrahydrocannabinol.

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