Atripla Side Effects

Generic Name: efavirenz / emtricitabine / tenofovir

Note: This page contains information about the side effects of efavirenz / emtricitabine / tenofovir. Some of the dosage forms included on this document may not apply to the brand name Atripla.

Not all side effects for Atripla may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to efavirenz / emtricitabine / tenofovir: oral tablet

In addition to its needed effects, some unwanted effects may be caused by efavirenz / emtricitabine / tenofovir. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking efavirenz / emtricitabine / tenofovir:

Less common
  • Abdominal or stomach pain or tenderness
  • blistering, peeling, or loosening of the skin
  • body aches or pain
  • clay-colored stools
  • cough
  • dark urine
  • ear congestion
  • fever or chills
  • headache
  • itching
  • loss of voice
  • muscle aches
  • nausea and vomiting
  • severe skin rash
  • sore throat
  • swelling of the feet or lower legs
  • tightness of the chest
  • trouble concentrating
  • yellow eyes or skin

Some of the side effects that can occur with efavirenz / emtricitabine / tenofovir may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Diarrhea
  • dizziness
  • unusual tiredness or weakness
Less common
  • Abnormal dreams
  • decreased appetite
  • discouragement
  • feeling sad or empty
  • irritability
  • loss of appetite
  • loss of interest or pleasure
  • mild rash
  • pain or tenderness around the eyes and cheekbones
  • sleepiness
  • trouble sleeping
  • unusual drowsiness

For Healthcare Professionals

Applies to efavirenz / emtricitabine / tenofovir: oral tablet

General

The most common side effects (10% or more; any severity) 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 were nervous system symptoms, psychiatric symptoms, and rash.

Hepatic

Common (1% to 10%): Elevated AST (greater than 180 units/L in males and 170 units/L in females: 3%), elevated ALT (greater than 215 units/L in males and 170 units/L in females: 2%)

Emtricitabine or tenofovir:
Common (1% to 10%): Elevated bilirubin (greater than 2.5 times upper limit of normal [ULN]: up to 3%)
Frequency not reported: Severe acute exacerbations of hepatitis B

Efavirenz:
Postmarketing reports: Hepatic enzyme increase, hepatic failure (a few reports were characterized by a fulminant course, with some cases progressing to transplantation or death), hepatitis

Emtricitabine:
Frequency not reported: Liver failure, liver decompensation

Tenofovir:
Frequency not reported: Lactic acidosis/severe hepatomegaly with steatosis
Postmarketing reports: Hepatic steatosis, hepatitis, increased liver enzymes (primarily AST, ALT, gamma glutamyltransferase)

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.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with nucleoside analogs, including tenofovir, in combination with other antiretrovirals.

Gastrointestinal

Common (1% to 10%): Diarrhea (Grades 2 to 4: 9%), nausea (Grades 2 to 4: 9%), vomiting (Grades 2 to 4: 2%)

Emtricitabine or tenofovir:
Common (1% to 10%): Dyspepsia (at least 5%), abdominal pain (at least 5%)

Efavirenz:
Common (1% to 10%): Anorexia (moderate to severe intensity: 2% or more), dyspepsia (moderate to severe intensity: 2% or more), abdominal pain (moderate to severe intensity: 2% or more)
Frequency not reported: Pancreatitis
Postmarketing reports: Constipation, malabsorption

Tenofovir:
Postmarketing reports: Pancreatitis, abdominal pain, increased amylase

Psychiatric

Serious psychiatric side effects associated with efavirenz have included severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions.

Common (1% to 10%): Depression (Grades 2 to 4: 9%), anxiety (Grades 2 to 4: 5%), insomnia (Grades 2 to 4: 5%)

Efavirenz:
Common (1% to 10%): Severe depression (2.4%), abnormal dreams (moderate to severe intensity: 2% or more), nervousness (moderate to severe intensity: 2% or more)
Uncommon (0.1% to 1%): Suicidal ideation (0.7%), nonfatal suicide attempts (0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%), manic reactions (0.2%)
Postmarketing reports: Aggressive reactions, agitation, delusions, emotional lability, mania neurosis, paranoia, psychosis, suicide

Dermatologic

Common (1% to 10%): Rash event (including rash, exfoliative rash, generalized rash, macular rash, maculopapular rash, pruritic rash, vesicular rash; Grades 2 to 4: 7%)

Emtricitabine or tenofovir:
Common (1% to 10%): Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, allergic reaction; at least 5%)

Efavirenz:
Very common (10% or more): Skin rash of any grade (26%), Grade 2 rash (diffuse maculopapular rash, dry desquamation; 14.7%), Grade 1 rash (erythema, pruritus; about 10%)
Common (1% to 10%): Pruritus (moderate to severe intensity: 2% or more)
Uncommon (0.1% to 1%): Grade 3 rash (vesiculation, moist desquamation, ulceration; less than 1%), Grade 4 rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, necrosis requiring surgery, exfoliative dermatitis; 0.1%)
Frequency not reported: Nail disorders, skin discoloration, leukocytoclastic vasculitis
Postmarketing reports: Erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome

Emtricitabine:
Frequency not reported: Skin discoloration (palmar-plantar hyperpigmentation)

Tenofovir:
Postmarketing reports: Rash

Rashes associated with efavirenz were usually mild-to-moderate maculopapular skin eruptions. The median time to onset of rash was 11 days. In most patients, the rash resolved within 1 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. Treatment was discontinued in 1.7% of patients due to rash.

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 2 of them discontinued efavirenz because of the rash.

Nervous system

Common (1% to 10%): Dizziness (Grades 2 to 4: 8%), headache (Grades 2 to 4: 6%)

Emtricitabine or tenofovir:
Common (1% to 10%): Paresthesia (at least 5%), peripheral neuropathy (including peripheral neuritis and neuropathy; at least 5%)

Efavirenz:
Very common (10% or more): Nervous system symptoms (any grade and regardless of causality: 53%), dizziness (28.1%), insomnia (16.3%)
Common (1% to 10%): Impaired concentration (8.3%), somnolence (7%), abnormal dreams (6.2%), Selected side effects of moderate to severe intensity have included impaired concentration (moderate to severe intensity: 2% or more), somnolence (moderate to severe intensity: 2% or more), hallucinations (1.2%)
Frequency not reported: Amnesia, agitation, euphoria, depersonalization, confusion, abnormal thinking, stupor
Postmarketing reports: Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, vertigo, tinnitus

Nervous system symptoms of any grade and regardless of causality (53%) included dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, hallucinations, 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.

Metabolic

Very common (10% or more): Elevated fasting cholesterol (greater than 240 mg/dL: up to 22%)
Common (1% to 10%): Elevated creatine kinase (greater than 990 units/L in males and 845 units/L in females: up to 9%), elevated serum amylase (greater than 175 units/L: up to 8%), elevated fasting triglycerides (greater than 750 mg/dL: 4%), altered serum glucose (less than 40 mg/dL or greater than 250 mg/dL: up to 3%), hyperglycemia (greater than 250 mg/dL: up to 2%), elevated alkaline phosphatase (greater than 550 units/L: 1%)
Frequency not reported: Increased body weight, redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")

Emtricitabine or tenofovir:
Common (1% to 10%): Elevated pancreatic amylase (greater than 2 times ULN: up to 3%), elevated serum lipase (greater than 2 times ULN: up to 3%)

Efavirenz:
Postmarketing reports: Hypercholesterolemia, hypertriglyceridemia

Tenofovir:
Postmarketing reports: Hypokalemia, lactic acidosis, hypophosphatemia

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

Respiratory

Common (1% to 10%): Sinusitis (Grades 2 to 4: 8%), upper respiratory tract infections (Grades 2 to 4: 8%), nasopharyngitis (Grades 2 to 4: 5%)

Emtricitabine or tenofovir:
Common (1% to 10%): Increased cough (at least 5%), pneumonia (at least 5%), rhinitis (at least 5%)

Efavirenz:
Postmarketing reports: Dyspnea

Tenofovir:
Postmarketing reports: Dyspnea

Renal

Tenofovir:
Frequency not reported: New onset or worsening renal impairment
Postmarketing reports: Renal insufficiency, renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, acute tubular necrosis, nephrogenic diabetes insipidus, interstitial nephritis (including acute cases)

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

Hematologic

Common (1% to 10%): Decreased neutrophils (less than 750/mm3: 3%)
Frequency not reported: Increased hemoglobin

Endocrine

Efavirenz:
Postmarketing reports: Gynecomastia

Tenofovir:
Frequency not reported: Higher serum parathyroid hormone levels

Cardiovascular

Efavirenz:
Frequency not reported: QT interval prolongation, torsades de pointes
Postmarketing reports: Palpitations

Musculoskeletal

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

Emtricitabine or tenofovir:
Common (1% to 10%): Arthralgia (at least 5%), myalgia (at least 5%)

Efavirenz:
Postmarketing reports: Arthralgia, myalgia, myopathy

Tenofovir:
Frequency not reported: Decreased bone mineral density, increased biochemical markers of bone metabolism
Postmarketing reports: Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy

Hypersensitivity

Efavirenz:
Postmarketing reports: Allergic reactions

Tenofovir:
Postmarketing reports: Allergic reaction (including angioedema)

Ocular

Efavirenz:
Postmarketing reports: Abnormal vision

Genitourinary

Common (1% to 10%): Hematuria (greater than 75 red blood cells/high power field: up to 3%)
Uncommon (0.1% to 1%): Glycosuria (3+ or greater: less than 1%)

Tenofovir:
Postmarketing reports: Proteinuria, polyuria

Immunologic

Frequency not reported: Immune reconstitution syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Other

Common (1% to 10%): Fatigue (Grades 2 to 4: 9%)

Emtricitabine or tenofovir:
Common (1% to 10%): Fever (at least 5%), pain (at least 5%), back pain (at least 5%)

Efavirenz:
Common (1% to 10%): Pain (moderate to severe intensity: 2% or greater)
Frequency not reported: False positive urine drug screening test results for tetrahydrocannabinol and benzodiazepines
Postmarketing reports: Flushing, contraceptive failure (with an implantable hormonal contraceptive), asthenia

Tenofovir:
Frequency not reported: Higher 1,25 vitamin D levels
Postmarketing reports: Asthenia

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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