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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].
  • 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.

Study 934 was an open-label active-controlled study in which 511 antiretroviral-naive patients 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 ≥ 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 studies 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 study, patients 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%

In addition to the adverse reactions in Study 934, 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 patients 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 ≥2% of efavirenz-treated patients 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 patients treated with efavirenz 600 mg than in control patients.

Emtricitabine and Tenofovir Disoproxil Fumarate: Adverse reactions that occurred in at least 5% of treatment-experienced or treatment-naive patients 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 patients; 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 studies (Table 3).

Table 3 Significant Laboratory Abnormalities Reported in ≥1% of Patients in Either Treatment Group in Study 934 (0—144 Weeks)
FTC + TDF + EFVFrom Weeks 96 to 144 of the study, patients 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%

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

Hepatic Events: In Study 934, 19 patients treated with efavirenz, emtricitabine, and tenofovir DF and 20 patients treated with efavirenz and fixed-dose zidovudine/lamivudine were hepatitis B surface antigen or hepatitis C antibody positive. Among these coinfected patients, one patient (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 patients (2/20) had elevations in transaminases to greater than five times ULN through 144 weeks. No HBV and/or HCV coinfected patient discontinued from the study 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

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

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 balancedisturbances, 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, nail disorders, photoallergic dermatitis, skin discoloration, Stevens-Johnson syndrome

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

Tenofovir Disoproxil Fumarate:

Immune System Disorders
Allergic reaction

Metabolism and Nutrition Disorders
Hypophosphatemia, lactic acidosis

Respiratory, Thoracic, and Mediastinal Disorders
Dyspnea

Gastrointestinal Disorders
Abdominal pain, increased amylase, pancreatitis

Hepatobiliary disorders
Increased liver enzymes (most commonly AST, ALT, gamma GT), hepatitis

Skin and Subcutaneous Tissue Disorders
Rash

Musculoskeletal and Connective Tissue Disorders
Myopathy, osteomalacia (both associated with proximal renal tubulopathy)

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

General Disorders and Administration Site Conditions
Asthenia



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: 2009-05-26

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