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Atripla (Efavirenz / Emtricitabine / Tenofovir Disoproxil Fumarate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Efavirenz, Emtricitabine and Tenofovir Disoproxil Fumarate: 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].
  • Psychiatric Symptoms [See Warnings and Precautions].
  • Nervous System Symptoms [See Warnings and Precautions].
  • New Onset or Worsening Renal Impairment [See Warnings and Precautions].
  • Rash [See Warnings and Precautions].
  • Hepatotoxicity [See Warnings and Precautions].
  • Decreases in Bone Mineral Density [See Warnings and Precautions].
  • Immune Reconstitution Syndrome [See Warnings and Precautions].
  • Drug Interactions [See Contraindications, Warnings and Precautions and Drug Interactions (7) ].

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.

Clinical Trials in Adult Subjects

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 ReactionsFrequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. (Grades 2–4) Reported in ≥5% in Either Treatment Group in Study 934 (0–144 Weeks)
FTC + TDF + EFVFrom 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. AZT/3TC + EFV
N=257 N=254
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 EventRash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular. 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], psychiatric symptoms [See Warnings and Precautions], and rash [See Warnings and Precautions].

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.

Clinical Trials in Pediatric Subjects

Efavirenz: In a pediatric clinical trial in 57 NRTI-experienced subjects aged 3 to 16 years, the type and frequency of adverse experiences was generally similar to that of adult subjects with the exception of a higher incidence of rash, which was reported in 46% (26/57) of pediatric subjects compared to 26% of adults, and a higher frequency of Grade 3 or 4 rash reported in 5% (3/57) of pediatric subjects compared to 0.9% of adults [See Warnings and Precautions]. For additional information, please consult the SUSTIVA prescribing information.

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 emtricitabine 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 tenofovir DF were consistent with those observed in clinical trials of tenofovir DF in adults [See Warnings and Precautions].

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 + EFVFrom 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. AZT/3TC + EFV
N=257 N=254
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 abnormalities of increased bilirubin (greater than 2.5 × upper limit of normal (ULN)), increased pancreatic amylase (greater than 2.0 × ULN), increased or decreased serum glucose (less than 40 or greater than 250 mg/dL), and increased serum lipase (greater than 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].

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], 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.



REPORTS OF SUSPECTED ATRIPLA SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Atripla. The information is not vetted and should not be considered as verified clinical evidence.

Possible Atripla side effects / adverse reactions in 54 year old male

Reported by a physician from United States on 2011-10-04

Patient: 54 year old male

Reactions: Vomiting, Nausea, Cough

Adverse event resulted in: hospitalization

Suspect drug(s):
Atripla

Erbitux
    Dosage: 447.5 mg total
    Indication: non-Small Cell Lung Cancer
    Start date: 2011-04-11

Carboplatin
    Dosage: 545 mg total
    Indication: non-Small Cell Lung Cancer
    Start date: 2011-04-11
    End date: 2011-01-01

Lortab

Fentanyl

Taxol
    Dosage: 269 mg total
    Indication: non-Small Cell Lung Cancer
    Start date: 2011-04-11
    End date: 2011-01-01



Possible Atripla side effects / adverse reactions in 37 year old female

Reported by a physician from United Kingdom on 2011-10-05

Patient: 37 year old female

Reactions: Overdose, Convulsion, Lower Respiratory Tract Infection

Suspect drug(s):
Efavirenz
    Dosage: 600 mg, qd
    Administration route: Oral
    Indication: HIV Infection
    Start date: 2010-03-01
    End date: 2010-08-01

Atripla
    Dosage: 1 df, qd
    Administration route: Oral
    Indication: HIV Infection
    Start date: 2010-03-01
    End date: 2010-08-01

Truvada
    Dosage: 1 df, qd
    Administration route: Oral
    Indication: HIV Infection
    Start date: 2010-03-01
    End date: 2010-08-01



Possible Atripla side effects / adverse reactions in 43 year old male

Reported by a pharmacist from United States on 2011-10-25

Patient: 43 year old male weighing 958.9 kg (2109.6 pounds)

Reactions: Paraesthesia

Suspect drug(s):
Atripla



See index of all Atripla side effect reports >>

Drug label data at the top of this Page last updated: 2013-05-03

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