Note: This document contains side effect information about emtricitabine / tenofovir. Some dosage forms listed on this page may not apply to the brand name AccessPak for HIV PEP Basic.

Applies to emtricitabine / tenofovir: oral tablet.

Serious side effects

Along with its needed effects, 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 emtricitabine / tenofovir:

More common

• Blisters under the skin
• body aches or pain
• chills
• difficulty in breathing
• ear congestion
• fever
• loss of voice
• pain or tenderness around the eyes and cheekbones
• rash with flat lesions or small raised lesions on the skin
• redness of the skin
• runny or stuffy nose
• sore throat
• spots on your skin resembling a blister or pimple
• unusual tiredness or weakness

Less common

• Blindness or vision changes
• burning of the face or mouth
• burning, crawling, itching, numbness, painful, prickling, "pins and needles", or tingling feelings in the hands, arms, feet, or legs
• chest pain
• clumsiness or unsteadiness
• stabbing pain
• weakness in the hands or feet

Incidence not known

• Agitation
• bloating
• bloody or cloudy urine
• bone pain
• change in how much or how often you urinate
• confusion
• constipation
• cough
• dark urine
• decreased awareness or responsiveness
• difficult or painful urination
• difficulty in swallowing
• fast heartbeat
• fast, shallow breathing
• general feeling of discomfort
• increased thirst
• indigestion
• irritability
• itching skin, hives, welts
• loss of appetite
• loss of consciousness
• lower back or side pain
• muscle pain, cramp, or twitching
• pains in the stomach, side, or abdomen, possibly radiating to the back
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• seizures
• severe sleepiness
• stomach pain
• sudden decrease in the amount of urine
• swelling of the face, fingers, hands, lower legs, or ankles
• tightness in the chest
• unusual drowsiness, dullness, or feeling of sluggishness
• yellow eyes or skin

Other side effects

Some side effects of 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

• Depression
• diarrhea
• nausea

Less common

• Anxiety
• back pain
• belching
• difficulty in moving
• heartburn
• joint pain or swelling
• lack or loss of strength
• pain
• passing of gas
• stomach upset
• sweating
• trouble sleeping
• vomiting
• weight loss

For Healthcare Professionals

Applies to emtricitabine / tenofovir: oral kit, oral tablet.

General

In clinical trials, the most common side effects reported with emtricitabine and tenofovir alafenamide (with elvitegravir and cobicistat) were nausea, diarrhea, and headache.

Side effects have been reported for emtricitabine and/or tenofovir disoproxil fumarate (DF) when taken in combination with other antiretroviral agents. The most common side effects reported in HIV-1-infected patients during a clinical study of efavirenz, emtricitabine, and tenofovir DF included diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. In this trial, emtricitabine-tenofovir DF (with efavirenz) was used from weeks 96 to 144, replacing emtricitabine plus tenofovir DF (with efavirenz).

In HIV-1-uninfected patients in HIV-1 preexposure prophylaxis trials, the most common side effect reported with emtricitabine-tenofovir alafenamide was diarrhea while the most common side effects reported with emtricitabine-tenofovir DF were headache, abdominal pain, and decreased weight.^[Ref]

Dermatologic

Skin discoloration (hyperpigmentation) was very common in pediatric patients using emtricitabine.

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

Emtricitabine-tenofovir DF:

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

Emtricitabine plus tenofovir alafenamide:

-Common (1% to 10%): Rash

-Uncommon (0.1% to 1%): Pruritus

Emtricitabine:

-Very common (10% or more): Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, allergic reaction)

-Common (1% to 10%): Skin discoloration (palmar-plantar hyperpigmentation)

-Frequency not reported: Lipodystrophy

-Postmarketing reports: Angioedema

Products containing emtricitabine and/or tenofovir alafenamide:

-Postmarketing reports: Angioedema, urticaria

Tenofovir alafenamide-containing products:

-Postmarketing reports: Angioedema, urticaria, rash

Tenofovir DF:

-Very common (10% or more): Rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash)

-Common (1% to 10%): Sweating

-Uncommon (0.1% to 1%): Lipodystrophy

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

Endocrine

Tenofovir DF:

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

Gastrointestinal

Increased serum amylase (greater than 175 units/L) has been reported in up to 8% of patients using emtricitabine-tenofovir DF.

In clinical trials, nausea was the most common side effect reported in antiretroviral therapy-naive HIV-1-infected patients using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat.

Increased amylase (greater than 2 times the upper limit of normal [2 x ULN]) has been reported in 3% and 5% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat. Increased lipase has been reported in 5% and 8% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat.

Pancreatitis, abdominal pain, and increased amylase have also been reported during postmarketing experience with tenofovir DF.^[Ref]

Emtricitabine-tenofovir alafenamide:

-Common (1% to 10%): Diarrhea, nausea, abdominal pain (included abdominal pain, upper abdominal pain, lower abdominal pain, gastrointestinal pain, abdominal discomfort)

Emtricitabine-tenofovir DF:

-Common (1% to 10%): Diarrhea, nausea, increased serum amylase, abdominal pain (included abdominal pain, upper abdominal pain, lower abdominal pain, gastrointestinal pain, abdominal discomfort), vomiting, increased lipase

-Frequency not reported: Flatulence

Emtricitabine plus tenofovir alafenamide:

-Very common (10% or more): Nausea

-Common (1% to 10%): Diarrhea, vomiting, abdominal pain, flatulence, increased amylase, increased lipase

-Uncommon (0.1% to 1%): Dyspepsia

Emtricitabine:

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

-Common (1% to 10%): Increased amylase (including increased pancreatic amylase), increased serum lipase, vomiting, dyspepsia

Tenofovir DF:

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

-Common (1% to 10%): Abdominal pain, abdominal distension, flatulence, dyspepsia, increased serum amylase

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

Genitourinary

Hematuria (greater than 75 RBC/high power field: up to 3%) and glycosuria (3+ or greater: less than 1%) have been reported with emtricitabine-tenofovir DF.

Hematuria (greater than 75 RBC/high power field) has been reported in 3% and 3% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat.

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

Emtricitabine-tenofovir DF:

-Common (1% to 10%): Proteinuria, urethritis, urinary tract infection, hematuria, genital ulceration, anogenital warts

-Uncommon (0.1% to 1%): Glycosuria

Emtricitabine plus tenofovir alafenamide:

-Common (1% to 10%): Hematuria

Tenofovir DF:

-Common (1% to 10%): Glycosuria, hematuria

-Uncommon (0.1% to 1%): Proteinuria

-Postmarketing reports: Polyuria^[Ref]

Hematologic

Decreased neutrophils (1000 to 1300 cells/mm3: up to 13%; less than 750 cells/mm3: up to 5%) and hemoglobin (8.5 to 10 mg/dL: 4%; less than 9.4 mg/dL: up to 2%) have been reported with emtricitabine-tenofovir DF.

Anemia was common in pediatric patients using emtricitabine.^[Ref]

Emtricitabine-tenofovir DF:

-Very common (10% or more): Decreased neutrophils (up to 13%)

-Common (1% to 10%): Decreased hemoglobin

Emtricitabine:

-Common (1% to 10%): Neutropenia

-Uncommon (0.1% to 1%): Anemia

Tenofovir DF:

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

Hepatic

Increased AST (1.25 to less than 2.5 x ULN: up to 14%; greater than 2.6 x ULN: up to 5%) and ALT (1.25 to less than 2.5 x ULN: up to 14%; greater than 2.6 x ULN: up to 7%) have been reported with emtricitabine-tenofovir DF.

Increased AST (greater than 180 units/L) and ALT (greater than 215 units/L) have been reported in 3% and 2% of males using emtricitabine-tenofovir DF, respectively. Increased AST (greater than 170 units/L) and ALT (greater than 170 units/L) have been reported in 3% and 2% of females using emtricitabine-tenofovir DF, respectively.

Increased AST (greater than 5 x ULN) has been reported in 3% and 4% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat. Increased ALT (greater than 5 x ULN) has been reported in 3% and 3% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat.

Severe acute exacerbations of hepatitis have been reported in patients with hepatitis B after discontinuation of this drug and were associated with liver failure and liver decompensation in some emtricitabine-treated patients.

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

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

Emtricitabine-tenofovir DF:

-Very common (10% or more): Increased AST (up to 14%), increased ALT (up to 14%)

-Frequency not reported: Severe acute exacerbations of hepatitis B

Emtricitabine plus tenofovir alafenamide:

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

Emtricitabine:

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

-Frequency not reported: Liver failure, liver decompensation, severe hepatomegaly with steatosis

Products containing emtricitabine and/or tenofovir alafenamide:

-Postmarketing reports: Autoimmune hepatitis

Tenofovir DF:

-Common (1% to 10%): Increased transaminases (AST and/or ALT)

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

-Frequency not reported: Severe hepatomegaly with steatosis

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

Hypersensitivity

Emtricitabine:

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

Tenofovir DF:

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

Immunologic

Emtricitabine-tenofovir DF:

-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)

Metabolic

Emtricitabine-tenofovir alafenamide:

-Common (1% to 10%): Fluid overload, hyperkalemia

Emtricitabine-tenofovir DF:

-Common (1% to 10%): Hyperglycemia

Emtricitabine:

-Common (1% to 10%): Hyperglycemia, hypertriglyceridemia, increased or decreased serum glucose

-Frequency not reported: Lactic acidosis

Tenofovir DF:

-Very common (10% or more): Hypophosphatemia

-Common (1% to 10%): Anorexia, increased serum glucose

-Uncommon (0.1% to 1%): Hypokalemia

-Rare (less than 0.1%): Lactic acidosis

Antiretroviral therapy:

-Frequency not reported: Redistribution of body fat (lipodystrophy), increased glucose levels^[Ref]

Hyperglycemia (greater than 250 mg/dL) has been reported in up to 2% of patients using emtricitabine-tenofovir DF.

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 DF.^[Ref]

Musculoskeletal

Emtricitabine-tenofovir alafenamide:

-Common (1% to 10%): Decreased bone mineral density (BMD), osteomyelitis

-Frequency not reported: Increased BMD

Emtricitabine-tenofovir DF:

-Very common (10% or more): Decreased BMD

-Common (1% to 10%): Increased creatine kinase, bone fractures, back pain

Emtricitabine plus tenofovir alafenamide:

-Very common (10% or more): Decreased BMD, increased creatine kinase

-Uncommon (0.1% to 1%): Arthralgia

-Frequency not reported: Increased biochemical markers of bone metabolism, increased BMD, fractures (excluding fingers and toes)

Emtricitabine:

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

-Common (1% to 10%): Myalgia, arthralgia

Tenofovir DF:

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

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

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

-Rare (less than 0.1%): Myopathy

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

-Postmarketing reports: Osteomalacia (manifested as bone pain and which may contribute to fractures)

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

In clinical trials of HIV-1-uninfected patients, decreased BMD was reported. During treatment with emtricitabine-tenofovir DF, 13% of patients lost at least 5% of BMD at the spine.

Increased creatine kinase (males: greater than 990 units/L; females: greater than 845 units/L) has been reported in up to 9% of patients using emtricitabine-tenofovir DF.

Increased creatine kinase (at least 10 x ULN) has been reported in 11% and 10% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat.

In virologically-suppressed tenofovir DF-treated patients who switched to emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean BMD increased between baseline and week 48; decreased BMD was also reported.

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

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

Nervous system

Emtricitabine-tenofovir alafenamide:

-Common (1% to 10%): Headache

Emtricitabine-tenofovir DF:

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

-Frequency not reported: Somnolence

Emtricitabine plus tenofovir alafenamide:

-Common (1% to 10%): Headache, dizziness

Emtricitabine:

-Very common (10% or more): Dizziness, headache

-Common (1% to 10%): Neuropathy/peripheral neuritis, paresthesia

Tenofovir DF:

-Very common (10% or more): Dizziness, headache

-Common (1% to 10%): Peripheral neuropathy (including neuropathy, peripheral neuritis)^[Ref]

Other

Increased fasting cholesterol (greater than 240 mg/dL: up to 22%), decreased phosphorus (2.5 to less than the lower limit of normal: up to 7%; less than 2 mg/dL: up to 10%), increased fasting triglycerides (greater than 750 mg/dL: up to 5%), and increased alkaline phosphatase (greater than 550 units/L: 1%) have been reported with emtricitabine-tenofovir DF.

In clinical trials, the following mean increases were reported in antiretroviral therapy-naive patients after using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat for 48 weeks: total cholesterol increased by 30 mg/dL, LDL cholesterol by 15 mg/dL, HDL cholesterol by 7 mg/dL, triglycerides by 29 mg/dL. In clinical trials, the following mean increases were reported in patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat for 144 weeks: fasted total cholesterol increased by 31 and 14 mg/dL, fasted LDL cholesterol by 20 and 8 mg/dL, fasted HDL cholesterol by 7 and 3 mg/dL, fasted triglycerides by 29 and 17 mg/dL.

Increased fasting LDL cholesterol (greater than 190 mg/dL) has been reported in 11% and 5% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat. Increased fasting total cholesterol (greater than 300 mg/dL) has been reported in 4% and 3% of patients using emtricitabine plus tenofovir alafenamide and emtricitabine plus tenofovir DF, respectively, each with elvitegravir plus cobicistat.

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

Emtricitabine-tenofovir alafenamide:

-Common (1% to 10%): Fatigue

-Frequency not reported: Decreased high-density lipoprotein (HDL) cholesterol (fasted), increased triglycerides (fasted), increased total cholesterol to HDL ratio

Emtricitabine-tenofovir DF:

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

-Common (1% to 10%): Fatigue, syphilis, secondary syphilis, decreased phosphorus, increased fasting triglycerides, weight decreased, increased alkaline phosphatase

-Frequency not reported: Decreased total cholesterol (fasted), decreased HDL cholesterol (fasted), decreased low-density lipoprotein (LDL) cholesterol (fasted), decreased triglycerides (fasted), increased total cholesterol to HDL ratio

Emtricitabine plus tenofovir alafenamide:

-Very common (10% or more): Increased fasting LDL cholesterol

-Common (1% to 10%): Fatigue, increased fasting total cholesterol

-Frequency not reported: Increased HDL cholesterol, increased triglycerides

Emtricitabine:

-Very common (10% or more): Asthenia

-Common (1% to 10%): Pain

Tenofovir DF:

-Very common (10% or more): Pain, asthenia, increased triglycerides

-Common (1% to 10%): Chest pain, fever, weight loss

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

Antiretroviral therapy:

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

Psychiatric

Emtricitabine-tenofovir DF:

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

Emtricitabine plus tenofovir alafenamide:

-Common (1% to 10%): Abnormal dreams

Emtricitabine:

-Very common (10% or more): Insomnia, abnormal dreams

-Common (1% to 10%): Depressive disorders

Tenofovir DF:

-Very common (10% or more): Depression

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

Renal

Increased creatinine (1.1 to 1.3 x ULN: up to 2%; greater than 1.4 x ULN: less than 1%) has been reported with emtricitabine-tenofovir DF.

In 2 trials in antiretroviral therapy-naive HIV-1-infected patients (median estimated glomerular filtration rate [eGFR] 115 mL/min at baseline) using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine increased by 0.1 mg/dL from baseline to week 48; median UPCR was 44 mg/g at baseline and at week 48. In a trial in virologically-suppressed tenofovir DF-treated patients (mean eGFR 112 mL/min at baseline) who switched to emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine was similar to baseline; median UPCR was 61 mg/g at baseline and 46 mg/g at week 48. In a trial in renal dysfunction patients (baseline eGFR 30 to 69 mL/min) using emtricitabine plus tenofovir alafenamide with elvitegravir plus cobicistat, mean serum creatinine was 1.5 mg/dL at baseline and week 24; median UPCR was 161 mg/g at baseline and 93 mg/g at week 24.

Proximal renal tubulopathy generally resolved or improved after tenofovir DF was stopped; however, decreased CrCl did not completely resolve in some HIV-1-infected patients after stopping the drug. Rhabdomyolysis, osteomalacia, bone abnormalities (infrequently contributing to fractures), 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, nephrogenic diabetes insipidus, and acute tubular necrosis have also been reported during postmarketing experience with tenofovir DF.^[Ref]

Emtricitabine-tenofovir alafenamide:

-Uncommon (0.1% to 1%): Increased urine protein-to-creatinine ratio (UPCR)

-Frequency not reported: Decreased serum creatinine, increased estimated glomerular filtration rate (eGFR)

Emtricitabine-tenofovir DF:

-Common (1% to 10%): Increased creatinine, increased UPCR

-Frequency not reported: Decreased eGFR

Emtricitabine plus tenofovir alafenamide:

-Frequency not reported: Increased serum creatinine, decreased UPCR, worsening renal function

Products containing emtricitabine and/or tenofovir alafenamide:

-Postmarketing reports: Acute renal failure, proximal renal tubulopathy, Fanconi syndrome

Tenofovir alafenamide-containing products:

-Postmarketing reports: Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, Fanconi syndrome

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, interstitial nephritis (including acute cases)

Tenofovir prodrugs:

-Frequency not reported: Renal impairment (including renal failure, Fanconi syndrome)^[Ref]

Respiratory

Emtricitabine-tenofovir alafenamide:

-Very common (10% or more): Pneumonia (up to 13%)

Emtricitabine-tenofovir DF:

-Very common (10% or more): Pharyngitis (up to 13%)

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

Emtricitabine:

-Very common (10% or more): Rhinitis, increased cough

Tenofovir DF:

-Common (1% to 10%): Pneumonia

-Postmarketing reports: Dyspnea^[Ref]