Summary

Commonly reported side effects of efavirenz/emtricitabine/tenofovir include: dizziness, insomnia, and skin rash. Other side effects include: drowsiness, lack of concentration, and abnormal dreams. Continue reading for a comprehensive list of adverse effects.

Applies to efavirenz / emtricitabine / tenofovir: oral tablet.

Serious side effects

Along with its needed effects, efavirenz / emtricitabine / tenofovir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking efavirenz / emtricitabine / tenofovir:

Less common

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

Other side effects

Some side effects of efavirenz / emtricitabine / tenofovir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Diarrhea
• dizziness

Less common

• Abnormal dreams
• decreased appetite
• decreased awareness or responsiveness
• discouragement
• feeling sad or empty
• irritability
• loss of appetite
• loss of interest or pleasure
• mild rash
• mimicry of speech or movements
• mutism
• negativism
• pain or tenderness around the eyes and cheekbones
• peculiar postures or movements, mannerisms or grimacing
• severe sleepiness
• trouble sleeping
• unusual drowsiness

For Healthcare Professionals

Applies to efavirenz / emtricitabine / tenofovir: oral tablet.

General

The most common side effects reported with this drug were psychiatric disorders, nervous system disorders, and gastrointestinal disorders. During a clinical trial using the individual components, the most common side effects were diarrhea, nausea, headache, fatigue, dizziness, depression, insomnia, abnormal dreams, and rash.

In general, the most common side effects associated with efavirenz in combination with other antiretroviral drugs of at least moderate severity included rash, dizziness, nausea, headache, and fatigue; the most significant side effects were nervous system symptoms, psychiatric symptoms, and rash.

In general, the most common side effects associated with emtricitabine in combination with other antiretroviral drugs of mild to moderate severity included headache, diarrhea, nausea, and rash; mild and asymptomatic skin discoloration (hyperpigmentation on the palms and/or soles) occurred more often with emtricitabine than the control treatment.

In general, the most common side effects associated with tenofovir disoproxil fumarate (DF) in combination with other antiretroviral drugs were mild to moderate gastrointestinal events, including nausea, diarrhea, vomiting, and flatulence.^[Ref]

Metabolic

Very common (10% or more): Elevated fasting cholesterol (up to 22%)

Common (1% to 10%): Anorexia, elevated fasting triglycerides, altered serum glucose, hyperglycemia, elevated alkaline phosphatase

Uncommon (0.1% to 1%): Increased appetite

Efavirenz:

-Common (1% to 10%): Anorexia, hypertriglyceridemia

-Uncommon (0.1% to 1%): Hypercholesterolemia

-Postmarketing reports: Redistribution/accumulation of body fat (in areas such as back of neck, breasts, abdomen, retroperitoneum)

Emtricitabine:

-Common (1% to 10%): Hyperglycemia, hypertriglyceridemia

Tenofovir DF:

-Very common (10% or more): Hypophosphatemia

-Uncommon (0.1% to 1%): Hypokalemia

-Rare (less than 0.1%): Lactic acidosis

Combination antiretroviral therapy:

-Frequency not reported: Redistribution of body fat (lipodystrophy)

Antiretroviral therapy:

-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased glucose levels^[Ref]

Elevated fasting cholesterol (greater than 240 mg/dL), elevated fasting triglycerides (greater than 750 mg/dL), altered serum glucose (less than 40 mg/dL or greater than 250 mg/dL), hyperglycemia (greater than 250 mg/dL), and elevated alkaline phosphatase (greater than 550 units/L) have been reported in up to 22%, 4%, up to 3%, up to 2%, and 1% of patients, respectively.

Hypercholesterolemia and hypertriglyceridemia have also been reported during postmarketing experience with efavirenz.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

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

Hypokalemia, lactic acidosis, and hypophosphatemia have also been reported during postmarketing experience with tenofovir.^[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, nausea, elevated serum amylase, vomiting

Uncommon (0.1% to 1%): Dry mouth

Emtricitabine or tenofovir DF:

-Common (1% to 10%): Dyspepsia, abdominal pain, elevated pancreatic amylase, elevated serum lipase

Efavirenz:

-Common (1% to 10%): Dyspepsia, abdominal pain, diarrhea, vomiting, nausea

-Uncommon (0.1% to 1%): Pancreatitis

-Postmarketing reports: Constipation, malabsorption

Emtricitabine:

-Very common (10% or more): Diarrhea, nausea

-Common (1% to 10%): Elevated amylase (including elevated pancreatic amylase), elevated serum lipase, vomiting, abdominal pain, dyspepsia

Tenofovir DF:

-Very common (10% or more): Diarrhea, vomiting, nausea

-Common (1% to 10%): Abdominal pain, abdominal distension, flatulence

-Uncommon (0.1% to 1%): Pancreatitis

-Postmarketing reports: Increased amylase^[Ref]

Elevated serum amylase (greater than 175 units/L) has been reported in up to 8% of patients.

Elevated pancreatic amylase (greater than 2 x ULN) and serum lipase (greater than 2 x ULN) have each been reported with emtricitabine or tenofovir in up to 3% of patients.

Pancreatitis and abdominal pain have also been reported during postmarketing experience with efavirenz and tenofovir.^[Ref]

Psychiatric

Common (1% to 10%): Depression, anxiety, insomnia

Uncommon (0.1% to 1%): Decreased libido

Efavirenz:

-Very common (10% or more): Insomnia (up to 16.3%)

-Common (1% to 10%): Depression, anxiety, severe depression, abnormal dreams, nervousness, hallucination

-Uncommon (0.1% to 1%): Suicidal ideation, nonfatal suicide attempts, aggression, paranoia, mania, psychosis, euphoric mood, affect/emotional lability, confusional state, agitation

-Frequency not reported: Depersonalization, delirium

-Postmarketing reports: Delusions, neurosis, psychosis-like behavior, completed suicide, catatonia

Emtricitabine:

-Common (1% to 10%): Insomnia, abnormal dreams^[Ref]

Serious psychiatric side effects associated with efavirenz have included severe depression, suicidal ideation, nonfatal suicide attempts, aggression, paranoia, and mania.

Aggression, agitation, affect lability, psychosis, paranoia, and mania have also been reported during postmarketing experience with efavirenz.^[Ref]

Nervous system

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; generally began the first or second day of therapy and often resolved after 2 to 4 weeks. Therapy was discontinued in 2.1% of patients due to these side effects.

Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, tremor, tinnitus, and vertigo have also been reported during postmarketing experience with efavirenz.^[Ref]

Common (1% to 10%): Dizziness, headache

Uncommon (0.1% to 1%): Incoherent speech

Emtricitabine or tenofovir DF:

-Common (1% to 10%): Paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy)

Efavirenz:

-Very common (10% or more): Nervous system symptoms (53%), dizziness (up to 28.1%)

-Common (1% to 10%): Impaired concentration, somnolence, cerebellar coordination and balance disturbances, headache, disturbance in attention

-Uncommon (0.1% to 1%): Convulsions, amnesia, abnormal thinking, ataxia, abnormal coordination, tremor, vertigo, tinnitus

-Frequency not reported: Stupor

-Postmarketing reports: Hypoesthesia, paresthesia, neuropathy, encephalopathy

Emtricitabine:

-Very common (10% or more): Headache

-Common (1% to 10%): Dizziness

Tenofovir DF:

-Very common (10% or more): Dizziness

-Common (1% to 10%): Headache^[Ref]

Dermatologic

Common (1% to 10%): Rash event (including rash, exfoliative rash, generalized rash, macular rash, maculopapular rash, pruritic rash, vesicular rash)

Emtricitabine or tenofovir DF:

-Common (1% to 10%): Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, allergic reaction)

Efavirenz:

-Very common (10% or more): Skin rash of any grade (up to 26.3%), grade 2 rash (diffuse maculopapular rash, dry desquamation; 14.7%), grade 1 rash (erythema, pruritus; 10.7%)

-Common (1% to 10%): Pruritus

-Uncommon (0.1% to 1%): Grade 3 rash (vesiculation, moist desquamation, ulceration), grade 4 rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, necrosis requiring surgery, exfoliative dermatitis)

-Rare (less than 0.1%): Photoallergic dermatitis

-Frequency not reported: Nail disorders, skin discoloration, leukocytoclastic vasculitis

Emtricitabine:

-Common (1% to 10%): Vesiculobullous rash, pustular rash, maculopapular rash, rash, pruritus, urticaria, skin discoloration (palmar-plantar hyperpigmentation)

-Postmarketing reports: Angioedema

Tenofovir DF:

-Very common (10% or more): Rash

-Rare (less than 0.1%): Angioedema^[Ref]

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 who continued therapy, the rash resolved within 1 month. Treatment was discontinued in 1.7% of patients due to rash.

There was limited experience using efavirenz in patients who previously discontinued other nonnucleoside reverse transcriptase inhibitors due to rash. In 19 such patients formerly on nevirapine, about half developed a mild to moderate rash; 2 of those patients discontinued efavirenz because of the rash.

Erythema multiforme, pruritus, photoallergic dermatitis, and Stevens-Johnson syndrome have also been reported during postmarketing experience with efavirenz. Rash has also been reported during postmarketing experience with tenofovir.^[Ref]

Other

False-positive urine cannabinoid test results have been reported with some screening assays in uninfected and HIV-infected patients receiving efavirenz.

Flushing and asthenia have also been reported during postmarketing experience with efavirenz and tenofovir, respectively.^[Ref]

Common (1% to 10%): Fatigue

Frequency not reported: Increased body weight

Emtricitabine or tenofovir DF:

-Common (1% to 10%): Fever, pain, back pain

Efavirenz:

-Common (1% to 10%): Pain, fatigue

-Uncommon (0.1% to 1%): Flushing

-Frequency not reported: False-positive urine cannabinoid test results

-Postmarketing reports: Contraceptive failure (with an implantable hormonal contraceptive), asthenia

Emtricitabine:

-Common (1% to 10%): Pain, asthenia

Tenofovir DF:

-Very common (10% or more): Asthenia

-Frequency not reported: Higher 1,25 vitamin D levels

Antiretroviral therapy:

-Frequency not reported: Increased weight, increased blood lipid levels^[Ref]

Respiratory

Common (1% to 10%): Sinusitis, upper respiratory tract infections, nasopharyngitis

Emtricitabine or tenofovir DF:

-Common (1% to 10%): Increased cough, pneumonia, rhinitis

Efavirenz:

-Postmarketing reports: Dyspnea

Tenofovir DF:

-Postmarketing reports: Dyspnea^[Ref]

Hepatic

Elevated AST (greater than 180 units/L in males and 170 units/L in females) and ALT (greater than 215 units/L in males and 170 units/L in females) have been reported in 3% and 2% of patients, respectively.

AST and ALT elevations were reported more often in patients who were coinfected with hepatitis B or C than in patients without coinfection.

Elevated bilirubin (greater than 2.5 times the upper limit of normal [2.5 x ULN]) has been reported with emtricitabine or tenofovir in up to 3% of patients.

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.

Hepatic steatosis and hepatitis have also been reported during postmarketing experience with tenofovir.^[Ref]

Common (1% to 10%): Elevated AST, elevated ALT

Emtricitabine or tenofovir DF:

-Common (1% to 10%): Elevated bilirubin

-Frequency not reported: Severe acute exacerbations of hepatitis B

Efavirenz:

-Common (1% to 10%): Elevated ALT, elevated AST, elevated GGT

-Uncommon (0.1% to 1%): Acute hepatitis

-Postmarketing reports: Hepatic enzyme increase, hepatic failure, hepatitis

Emtricitabine:

-Common (1% to 10%): Elevated serum AST and/or elevated serum ALT, hyperbilirubinemia

-Frequency not reported: Liver failure, liver decompensation

Tenofovir DF:

-Common (1% to 10%): Increased transaminases

-Rare (less than 0.1%): Hepatic steatosis, hepatitis

-Frequency not reported: Lactic acidosis/severe hepatomegaly with steatosis

-Postmarketing reports: Elevated liver enzymes (primarily AST, ALT, GGT)^[Ref]

Hematologic

Common (1% to 10%): Decreased neutrophils

Frequency not reported: Increased hemoglobin

Emtricitabine:

-Common (1% to 10%): Neutropenia

-Uncommon (0.1% to 1%): Anemia^[Ref]

Decreased neutrophils (less than 750/mm3) has been reported in 3% of patients.^[Ref]

Musculoskeletal

Elevated creatine kinase (greater than 990 units/L in males and 845 units/L in females) has been reported in up to 9% of patients.

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

Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy have also been reported during postmarketing experience with tenofovir.^[Ref]

Common (1% to 10%): Elevated creatine kinase

Uncommon (0.1% to 1%): Myalgia

Emtricitabine or tenofovir DF:

-Common (1% to 10%): Arthralgia, myalgia

Emtricitabine:

-Very common (10% or more): Elevated creatine kinase

Efavirenz:

-Postmarketing reports: Arthralgia, myalgia, myopathy

Tenofovir DF:

-Uncommon (0.1% to 1%): Rhabdomyolysis, muscular weakness

-Rare (less than 0.1%): Myopathy, osteomalacia (manifested as bone pain and infrequently contributing to fractures)

-Frequency not reported: Decreased bone mineral density, increased biochemical markers of bone metabolism

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

Genitourinary

Hematuria (greater than 75 red blood cells/high power field) and glycosuria (3+ or greater) have been reported in up to 3% and less than 1% of patients, respectively.

Proteinuria has also been reported during postmarketing experience with tenofovir.^[Ref]

Common (1% to 10%): Hematuria

Uncommon (0.1% to 1%): Glycosuria

Tenofovir DF:

-Uncommon (0.1% to 1%): Proteinuria

-Postmarketing reports: Polyuria^[Ref]

Renal

Tenofovir DF:

-Uncommon (0.1% to 1%): Increased creatinine, proximal renal tubulopathy (including Fanconi syndrome)

-Rare (less than 0.1%): Renal failure (acute and chronic), acute tubular necrosis, nephrogenic diabetes insipidus

-Frequency not reported: New onset or worsening renal impairment

-Postmarketing reports: Renal insufficiency, nephritis (including acute interstitial nephritis)^[Ref]

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

Renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, acute tubular necrosis, and nephrogenic diabetes insipidus have also been reported during postmarketing experience with tenofovir.^[Ref]

Immunologic

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

Efavirenz-, Emtricitabine-, and/or Tenofovir DF-Containing Products:

-Postmarketing reports: Autoimmune hepatitis, immune reconstitution syndrome^[Ref]

Hypersensitivity

Efavirenz:

-Uncommon (0.1% to 1%): Hypersensitivity

-Postmarketing reports: Allergic reactions

Emtricitabine:

-Common (1% to 10%): Allergic reaction

Tenofovir DF:

-Postmarketing reports: Allergic reaction (including angioedema)^[Ref]

Cardiovascular

Efavirenz:

-Frequency not reported: QT interval prolongation, torsades de pointes

-Postmarketing reports: Palpitations^[Ref]

Endocrine

Efavirenz:

-Uncommon (0.1% to 1%): Gynecomastia

Tenofovir DF:

-Frequency not reported: Higher serum parathyroid hormone levels^[Ref]

Gynecomastia has also been reported during postmarketing experience with efavirenz.^[Ref]

Ocular

Efavirenz:

-Uncommon (0.1% to 1%): Blurred vision

-Postmarketing reports: Abnormal vision^[Ref]

Blurred vision has also been reported during postmarketing experience with efavirenz.^[Ref]