Applies to efavirenz / lamivudine / tenofovir: oral tablet.

Serious side effects

Along with its needed effects, efavirenz / lamivudine / 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 / lamivudine / tenofovir:

More common

• Anxiety
• discouragement
• feeling sad or empty
• fever
• irritability
• lack of appetite
• loss of interest or pleasure
• rash
• stomach pain
• trouble concentrating
• trouble sleeping

Less common

• Body aches or pain
• burning, numbness, tingling, or painful sensations
• chest pain
• chills
• cough
• diarrhea
• difficulty in moving
• ear congestion
• headache
• joint pain
• loss of voice
• muscle cramp, pain, or stiffness
• nausea
• painful blisters on the trunk of the body
• runny or stuffy nose
• sneezing
• sore throat
• swollen joints
• tightness in the chest
• troubled breathing
• unsteadiness or awkwardness
• unusual tiredness or weakness
• weakness in the arms, hands, legs, or feet

Incidence not known

• Agitation
• blistering, peeling, loosening of the skin
• bloating
• bone fractures, especially of the femur
• bone pain
• dark urine
• decreased appetite
• decreased awareness or responsiveness
• decreased urine
• difficulty having a bowel movement (stool)
• dizziness
• dry mouth
• fast, irregular heartbeat
• fast, shallow breathing
• general feeling of discomfort
• general feeling of tiredness or weakness
• hostility
• increased thirst
• indigestion
• itching
• light-colored stools
• loss of bone mineral density
• loss of consciousness
• mood changes
• muscle twitching
• pains in the stomach, side, or abdomen, possibly radiating to the back
• rapid weight gain
• red skin lesions, often with a purple center
• red, irritated eye
• seizures
• severe sleepiness
• sleepiness
• sores, ulcers, or white spots in the mouth or on the lips
• stomach discomfort
• stomach pain, continuing
• swelling of the face, ankles, or hands
• upper right abdominal or stomach pain
• vomiting
• yellow eyes or skin

Other side effects

Some side effects of efavirenz / lamivudine / 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

• Back pain
• lack or loss of strength

Less common

• Abnormal dreams
• belching
• heartburn
• indigestion
• redistribution or accumulation of body fat

For Healthcare Professionals

Applies to efavirenz / lamivudine / tenofovir: oral tablet.

General

In a controlled trial with efavirenz, lamivudine, and tenofovir disoproxil fumarate (DF), the most common side effects were mild-to-moderate gastrointestinal events and dizziness. Mild side effects (grade 1) were common and included dizziness, diarrhea, and nausea.

In a controlled trial with efavirenz (400 or 600 mg) in combination with fixed-dose emtricitabine-tenofovir DF, the most common side effects were mild-to-moderate gastrointestinal events, dizziness, abnormal dreams, and rash.^[Ref]

Nervous system

Very common (10% or more): Headache (14%)

Common (1% to 10%): Dizziness

Uncommon (0.1% to 1%): Peripheral neuropathy (included peripheral neuritis, neuropathy)

Efavirenz (with emtricitabine-tenofovir DF):

-Very common (10% or more): Dizziness (up to 35%), headache (up to 11%)

-Common (1% to 10%): Herpes zoster, somnolence

Efavirenz:

-Very common (10% or more): Central nervous system symptoms (53%), dizziness (28.1%)

-Common (1% to 10%): Impaired concentration, somnolence

-Postmarketing reports: Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, vertigo, tinnitus^[Ref]

Central nervous system (CNS) symptoms were reported in 53% of patients using efavirenz; these symptoms generally began the first or second day of therapy and often resolved after 2 to 4 weeks. CNS symptoms (any grade, regardless of causality) included, but were not limited to, dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, and hallucinations. These symptoms were severe in 2% of patients; therapy was discontinued in 2.1% of patients due to these side effects. After 4 weeks of therapy, CNS symptoms of at least moderate severity were reported in 5% to 9% of patients using efavirenz-containing regimens.^[Ref]

Dermatologic

Very common (10% or more): Rash event (included rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash; 18%)

Efavirenz (with emtricitabine-tenofovir DF):

-Very common (10% or more): Rash event (included allergic dermatitis, drug hypersensitivity, generalized pruritus, eosinophilic pustular folliculitis, rash, erythematous rash, generalized rash, macular rash, maculopapular rash, morbilliform rash, papular rash, pruritic rash, vesicular rash, urticaria; up to 32%)

-Common (1% to 10%): Grade 3 to 4 rash

Efavirenz:

-Very common (10% or more): New-onset skin rash (26%)

-Uncommon (0.1% to 1%): Rash associated with blistering/moist desquamation/ulceration, grade 4 rash (e.g., erythema, multiforme, Stevens-Johnson syndrome)

-Postmarketing reports: Erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome

Lamivudine:

-Postmarketing reports: Urticaria, alopecia, pruritus

Tenofovir DF:

-Postmarketing reports: Rash^[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 due to rash in 1.7% of patients.^[Ref]

Metabolic

Very common (10% or more): Elevated fasting cholesterol (19%)

Uncommon (0.1% to 1%): Lipodystrophy, elevated fasting triglycerides

Frequency not reported: Higher 1,25 vitamin D levels

Efavirenz (with emtricitabine-tenofovir DF):

-Common (1% to 10%): Cholesterol abnormal

Efavirenz:

-Postmarketing reports: Hypercholesterolemia, hypertriglyceridemia, redistribution/accumulation of body fat

Lamivudine:

-Postmarketing reports: Hyperglycemia, lactic acidosis, redistribution/accumulation of body fat

Tenofovir DF:

-Postmarketing reports: Lactic acidosis, hypokalemia, hypophosphatemia

Combination antiretroviral therapy:

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

Elevated fasting cholesterol (greater than 240 mg/dL) and fasting triglycerides (greater than 750 mg/dL) have been reported in 19% and 1% of patients using efavirenz, lamivudine, and tenofovir DF, respectively.

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.^[Ref]

Other

False-positive urine cannabinoid test results have been observed with some screening assays in uninfected and HIV-infected subjects using efavirenz.^[Ref]

Very common (10% or more): Pain (13%)

Common (1% to 10%): Fever, asthenia

Efavirenz (with emtricitabine-tenofovir DF):

-Common (1% to 10%): Pyrexia, phosphorus abnormal

Efavirenz:

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

-Postmarketing reports: Asthenia, flushing

Lamivudine:

-Postmarketing reports: Weakness

Tenofovir DF:

-Postmarketing reports: Asthenia^[Ref]

Musculoskeletal

Very common (10% or more): Elevated creatine phosphokinase (12%)

Common (1% to 10%): Back pain, arthralgia, myalgia

Frequency not reported: Decreased bone mineral density, increased biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C telopeptide, urinary N telopeptide), clinically relevant fractures (excluding fingers and toes)

Efavirenz:

-Postmarketing reports: Arthralgia, myalgia, myopathy

Lamivudine:

-Postmarketing reports: Muscle weakness, elevated creatine phosphokinase, rhabdomyolysis

Tenofovir DF:

-Postmarketing reports: Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy^[Ref]

Elevated creatine phosphokinase (males: greater than 990 units/L; females: greater than 845 units/L) has been reported in 12% of patients using efavirenz, lamivudine, and tenofovir DF.

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

Gastrointestinal

Very common (10% or more): Diarrhea (11%)

Common (1% to 10%): Nausea, increased serum amylase, abdominal pain, dyspepsia, vomiting

Efavirenz (with emtricitabine-tenofovir DF):

-Common (1% to 10%): Diarrhea, vomiting, gastroenteritis

Efavirenz:

-Postmarketing reports: Constipation, malabsorption

Lamivudine:

-Frequency not reported: Pancreatitis

Tenofovir DF:

-Postmarketing reports: Pancreatitis, increased amylase, abdominal pain^[Ref]

Increased serum amylase (greater than 175 units/L) has been reported in 9% of patients using efavirenz, lamivudine, and tenofovir DF.

Pancreatitis (some cases fatal) has been reported in antiretroviral nucleoside-experienced pediatric patients using lamivudine alone or in combination with other antiretroviral agents.^[Ref]

Psychiatric

Very common (10% or more): Depression (11%)

Common (1% to 10%): Anxiety, insomnia, abnormal dreams

Efavirenz (with emtricitabine-tenofovir DF):

-Common (1% to 10%): Insomnia, abnormal dreams, depression, sleep disorder, nightmare, anxiety

Efavirenz:

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

-Common (1% to 10%): Severe depression, abnormal dreams, hallucinations

-Uncommon (0.1% to 1%): Suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, manic reactions

-Postmarketing reports: Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide, catatonia^[Ref]

Genitourinary

Hematuria (greater than 100 RBC/high power field) has been reported in 7% of patients using efavirenz, lamivudine, and tenofovir DF.^[Ref]

Common (1% to 10%): Hematuria

Tenofovir DF:

-Postmarketing reports: Proteinuria, polyuria^[Ref]

Hepatic

Elevated AST (males: greater than 180 units/L; females: greater than 170 units/L) and ALT (males: greater than 215 units/L; females: greater than 170 units/L) have been reported in 5% and 4% patients using efavirenz, lamivudine, and tenofovir DF, respectively.

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

Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and hepatitis B virus after discontinuation of lamivudine or tenofovir DF.

Hepatic decompensation (some fatal) has been reported in patients coinfected with HIV-1 and hepatitis C receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin.^[Ref]

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

Efavirenz (with emtricitabine-tenofovir DF):

-Common (1% to 10%): ALT abnormal, AST abnormal

-Uncommon (0.1% to 1%): Bilirubin abnormal

Efavirenz:

-Postmarketing reports: Increased hepatic enzymes, hepatic failure, hepatitis (including fulminant hepatitis progressing to liver failure requiring transplantation or resulting in death)

Lamivudine:

-Postmarketing reports: Hepatic steatosis, posttreatment exacerbation of hepatitis B

Tenofovir DF:

-Postmarketing reports: Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT, GGT)

Combination antiretroviral therapy:

-Frequency not reported: Hepatic decompensation^[Ref]

Hematologic

Decreased neutrophils (less than 750/mm3) has been reported in 3% of patients using efavirenz, lamivudine, and tenofovir DF.^[Ref]

Common (1% to 10%): Decreased neutrophils

Efavirenz (with emtricitabine-tenofovir DF):

-Common (1% to 10%): Neutrophils abnormal

Lamivudine:

-Postmarketing reports: Anemia (including pure red cell aplasia and severe anemias progressing on therapy)^[Ref]

Respiratory

Common (1% to 10%): Pneumonia

Efavirenz (with emtricitabine-tenofovir DF):

-Common (1% to 10%): Upper respiratory tract infection, nasopharyngitis

Efavirenz:

-Postmarketing reports: Dyspnea

Tenofovir DF:

-Postmarketing reports: Dyspnea^[Ref]

Renal

Tenofovir DF:

-Postmarketing reports: Renal insufficiency, acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, increased creatinine^[Ref]

Hypersensitivity

Efavirenz:

-Postmarketing reports: Allergic reactions

Lamivudine:

-Postmarketing reports: Anaphylaxis

Tenofovir DF:

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

Cardiovascular

Efavirenz:

-Frequency not reported: QTc prolongation

-Postmarketing reports: Palpitations^[Ref]

Immunologic

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

Endocrine

Frequency not reported: Higher serum parathyroid hormone levels

Efavirenz:

-Postmarketing reports: Gynecomastia^[Ref]

Ocular

Efavirenz:

-Postmarketing reports: Abnormal vision^[Ref]