Note: This document contains side effect information about emtricitabine / rilpivirine / tenofovir alafenamide. Some dosage forms listed on this page may not apply to the brand name Odefsey.

Summary

Common side effects of Odefsey include: depression. Other side effects include: skin rash. Continue reading for a comprehensive list of adverse effects.

Applies to emtricitabine / rilpivirine / tenofovir alafenamide: oral tablet.

Serious side effects of Odefsey

Along with its needed effects, emtricitabine / rilpivirine / tenofovir alafenamide 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 / rilpivirine / tenofovir alafenamide:

More common

• Discouragement
• feeling sad or empty
• irritability
• lack of appetite
• loss of interest or pleasure
• mental depression
• thoughts of killing oneself
• tiredness
• trouble concentrating
• trouble sleeping

Less common

• Body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• chills
• cough
• difficulty with breathing
• ear congestion
• fever
• headache
• loss of voice
• runny or stuffy nose
• sneezing
• sore throat
• tightness in the chest
• unsteadiness or awkwardness
• unusual tiredness or weakness
• weakness in the arms, hands, legs, or feet

Incidence not known

• Agitation
• bloating
• bloody or cloudy urine
• confusion
• constipation
• dark urine
• decreased appetite
• decreased urination
• diarrhea
• difficulty swallowing
• dizziness
• dry mouth
• fast heartbeat
• fast, shallow breathing
• frequent urination
• hostility
• increased thirst
• indigestion
• irritability
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• light-colored stools
• muscle pain or cramps
• muscle tenderness, wasting, or weakness
• nausea
• pain in the stomach, side, or abdomen, possibly radiating to the back
• rapid weight gain
• seizures
• skin rash, hives, itching
• sleepiness
• stomach discomfort
• swelling of the face, ankles, hands, feet, or lower legs
• unusual drowsiness, dullness, or feeling of sluggishness
• vomiting
• yellow eyes or skin

Other side effects of Odefsey

Some side effects of emtricitabine / rilpivirine / tenofovir alafenamide 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

• Abnormal dreams

Less common

• Back pain
• belching
• difficulty with moving
• heartburn
• pain in the joints
• pain or tenderness around the eyes and cheekbones
• stomach discomfort or upset

Incidence not known

• Lack or loss of strength

For Healthcare Professionals

Applies to emtricitabine / rilpivirine / tenofovir alafenamide: oral tablet.

General

The most common side effects reported with emtricitabine / rilpivirine / tenofovir alafenamide in virologically-suppressed patients with HIV-1 infection were headache and sleep disturbances.

During clinical studies, antiretroviral therapy-naive patients received rilpivirine in combination with emtricitabine-tenofovir disoproxil fumarate (DF). The most common side effects were depression/depressive disorders, nausea, dizziness, abnormal dreams, headache, diarrhea, and insomnia. In virologically-suppressed patients switching to emtricitabine/rilpivirine/tenofovir DF, the most common side effects were fatigue, diarrhea, nausea, and insomnia.

The manufacturer product information for emtricitabine, rilpivirine, tenofovir alafenamide, and tenofovir DF should be consulted.^[Ref]

Gastrointestinal

Increased pancreatic amylase (greater than 2 times the upper limit of normal [2 x ULN]) and lipase (greater than 3 x ULN) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

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 x ULN) and lipase have been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF; lipase test was performed only for patients with serum amylase greater than 1.5 x ULN.

Diarrhea and nausea have been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Abdominal pain, dyspepsia, and vomiting have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.

Increased pancreatic amylase (greater than 2 x ULN), serum amylase (greater than 175 units/L), and lipase (greater than 3 x ULN) have been reported with emtricitabine and/or tenofovir DF.^[Ref]

Emtricitabine / rilpivirine / tenofovir alafenamide:

-Common (1% to 10%): Flatulence, diarrhea, nausea

Emtricitabine/rilpivirine/tenofovir DF:

-Common (1% to 10%): Diarrhea, nausea

Emtricitabine-tenofovir DF plus rilpivirine:

-Common (1% to 10%): Nausea, increased pancreatic amylase

-Uncommon (0.1% to 1%): Increased lipase

Emtricitabine and tenofovir alafenamide:

-Very common (10% or more): Nausea

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

Emtricitabine and/or tenofovir DF:

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

-Common (1% to 10%): Abdominal pain, dyspepsia, vomiting, increased serum amylase, increased lipase

-Frequency not reported: Increased pancreatic amylase

-Postmarketing reports: Increased amylase, abdominal pain, pancreatitis

Emtricitabine:

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

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

Rilpivirine:

-Very common (10% or more): Nausea, increased pancreatic amylase, vomiting

-Common (1% to 10%): Diarrhea, abdominal discomfort, abdominal pain, increased lipase, dry mouth

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, pancreatitis, abdominal pain^[Ref]

Nervous system

Headache and dizziness have been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Paresthesia and peripheral neuropathy (including peripheral neuritis and neuropathy) have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.^[Ref]

Emtricitabine / rilpivirine / tenofovir alafenamide:

-Common (1% to 10%): Headache

Emtricitabine-tenofovir DF plus rilpivirine:

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

Emtricitabine and tenofovir alafenamide:

-Very common (10% or more): Headache, dizziness

Emtricitabine and/or tenofovir DF:

-Very common (10% or more): Headache, dizziness

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

Emtricitabine:

-Very common (10% or more): Headache, dizziness

Rilpivirine:

-Very common (10% or more): Headache, dizziness

-Common (1% to 10%): Somnolence

Tenofovir DF:

-Very common (10% or more): Dizziness, headache^[Ref]

Psychiatric

Depression, insomnia, and abnormal dreams have been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Anxiety has been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.

During Phase 3 trials through 96 weeks, depressive disorders (regardless of causality, severity) were reported in 9% of patients receiving rilpivirine.^[Ref]

Emtricitabine / rilpivirine / tenofovir alafenamide:

-Common (1% to 10%): Sleep disturbances, abnormal dreams

Emtricitabine/rilpivirine/tenofovir DF:

-Common (1% to 10%): Insomnia

Emtricitabine-tenofovir DF plus rilpivirine:

-Common (1% to 10%): Depression, depressive disorders (reported as depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation), insomnia, abnormal dreams

Emtricitabine and tenofovir alafenamide:

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

Emtricitabine and/or tenofovir DF:

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

-Common (1% to 10%): Anxiety

Emtricitabine:

-Very common (10% or more): Insomnia

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

Rilpivirine:

-Very common (10% or more): Insomnia

-Common (1% to 10%): Depressive disorders, abnormal dreams, depression, sleep disorders, depressed mood

-Frequency not reported: Anxiety^[Ref]

Musculoskeletal

Emtricitabine / rilpivirine / tenofovir alafenamide:

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

-Frequency not reported: Increased BMD

Emtricitabine/rilpivirine/tenofovir DF:

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

Emtricitabine and tenofovir alafenamide:

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

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

-Uncommon (0.1% to 1%): Arthralgia

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

Emtricitabine and/or tenofovir DF:

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

-Frequency not reported: Increased creatine kinase

-Postmarketing reports: Rhabdomyolysis, muscular weakness, myopathy, osteomalacia (manifested as bone pain and infrequently contributing to fractures)

Emtricitabine:

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

Tenofovir DF:

-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, bone abnormalities

-Postmarketing reports: Osteomalacia (manifested as bone pain and infrequently contributing to fractures), rhabdomyolysis, muscular weakness, myopathy

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

In 2 trials, BMD increased in patients who switched to emtricitabine / rilpivirine / tenofovir alafenamide and remained stable or decreased in patients who remained on emtricitabine/rilpivirine/tenofovir DF. BMD decreases occurred more often in patients using emtricitabine/rilpivirine/tenofovir DF than those using emtricitabine / rilpivirine / tenofovir alafenamide.

Arthralgia, back pain, and myalgia have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.

Increased creatine kinase (at least 10 x ULN) has been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF. Increased creatine kinase (males: greater than 990 units/L; females: greater than 845 units/L) has been reported with emtricitabine or tenofovir DF.

Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy may occur due to proximal renal tubulopathy.^[Ref]

Other

Emtricitabine / rilpivirine / tenofovir alafenamide:

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

Emtricitabine/rilpivirine/tenofovir DF:

-Common (1% to 10%): Fatigue

-Frequency not reported: Increased fasted LDL cholesterol, decreased fasted triglycerides, increased total cholesterol to HDL ratio, decreased fasted total cholesterol, decreased fasted HDL cholesterol, decreased fasted LDL cholesterol, increased fasted triglycerides

-Postmarketing reports: Weight increased

Emtricitabine-tenofovir DF plus rilpivirine:

-Very common (10% or more): Increased fasted total cholesterol (up to 14%), increased fasted LDL cholesterol (up to 13%)

-Common (1% to 10%): Increased fasted triglycerides, fatigue

Emtricitabine and tenofovir alafenamide:

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

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

-Frequency not reported: Increased total cholesterol, increased LDL cholesterol, increased HDL cholesterol, increased triglycerides

Emtricitabine and/or tenofovir DF:

-Very common (10% or more): Fatigue

-Common (1% to 10%): Fever, pain, increased fasted LDL cholesterol, increased fasted total cholesterol

-Frequency not reported: Increased alkaline phosphatase

-Postmarketing reports: Asthenia

Emtricitabine:

-Very common (10% or more): Asthenia

-Common (1% to 10%): Pain

Rilpivirine:

-Very common (10% or more): Increased fasted total cholesterol, increased fasted LDL cholesterol

-Common (1% to 10%): Fatigue, increased fasted triglycerides

-Postmarketing reports: Weight increased

Tenofovir DF:

-Very common (10% or more): Asthenia

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

-Postmarketing reports: Asthenia

Antiretroviral therapy:

-Frequency not reported: Increased weight^[Ref]

In patients using emtricitabine / rilpivirine / tenofovir alafenamide from baseline to week 48, fasted total cholesterol, fasted HDL cholesterol, fasted LDL cholesterol, and fasted triglycerides increased in 1 trial and decreased in another trial; total cholesterol to HDL ratio increased in both trials. In patients using emtricitabine/rilpivirine/tenofovir DF from baseline to week 48, fasted total cholesterol and fasted HDL cholesterol did not change, fasted LDL cholesterol increased, fasted triglycerides decreased, and total cholesterol to HDL ratio increased in 1 trial while in another trial fasted total cholesterol, fasted HDL cholesterol, and fasted LDL cholesterol decreased, fasted triglycerides increased, and total cholesterol to HDL ratio did not change.

Increased fasted total cholesterol (grade 1: 14%; grade 2: 6%; grade 3: less than 1%), fasted LDL cholesterol (grade 1: 13%; grade 2: 5%; grade 3: 1%) and fasted triglycerides (grade 2: 1%; grade 3: 1%) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

Increased fasted total cholesterol (greater than 300 mg/dL), fasted LDL cholesterol (greater than 191 mg/dL), and fasted triglycerides (greater than 751 mg/dL) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

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, and triglycerides by 29 mg/dL.

Increased fasted LDL cholesterol (greater than 190 mg/dL) and fasted total cholesterol (greater than 300 mg/dL) have been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF.

Increased alkaline phosphatase (greater than 550 units/L) has been reported with emtricitabine or tenofovir DF.

Other side effects have included fatigue in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF. Fever and pain have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.^[Ref]

Renal

Emtricitabine / rilpivirine / tenofovir alafenamide:

-Frequency not reported: Decreased serum creatinine, increased serum creatinine

Emtricitabine-tenofovir DF plus rilpivirine:

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

Emtricitabine and tenofovir alafenamide:

-Frequency not reported: Increased serum creatinine, decreased urine protein-to-creatinine ratio (UPCR), worsening renal function

Emtricitabine and/or tenofovir DF:

-Postmarketing reports: Increased creatinine, renal insufficiency, renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, nephrogenic diabetes insipidus, acute tubular necrosis, interstitial nephritis (including acute cases)

Rilpivirine:

-Common (1% to 10%): Membranous glomerulonephritis, mesangioproliferative glomerulonephritis, nephrolithiasis

-Frequency not reported: Increased serum creatinine, decreased estimated glomerular filtration rate (eGFR)

-Frequency not reported: Membranous glomerulonephritis, mesangioproliferative glomerulonephritis, nephrolithiasis

-Postmarketing reports: Nephrotic 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, nephritis (including acute interstitial nephritis), renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, nephrogenic diabetes insipidus, acute tubular necrosis

Tenofovir prodrugs:

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

In 1 trial, baseline eGFR averaged 104 mL/min for patients who switched to emtricitabine / rilpivirine / tenofovir alafenamide from emtricitabine/rilpivirine/tenofovir DF; serum creatinine decreased by 0.02 mg/dL from baseline to week 48. In another trial, baseline eGFR averaged 110 mL/min for patients who switched to emtricitabine / rilpivirine / tenofovir alafenamide from emtricitabine/rilpivirine/tenofovir DF; serum creatinine increased by 0.1 mg/dL from baseline to week 48.

Increased creatinine (grade 1: 6%; grade 2: 1%; grade 3: less than 1%) has been reported with emtricitabine-tenofovir DF plus rilpivirine.

During phase 3 trials, an increase in serum creatinine and decrease in eGFR were seen over 96 weeks of therapy with rilpivirine. Most of these changes occurred within the first 4 weeks of therapy, with a mean change of 0.1 mg/dL (range: -0.3 to 0.6 mg/dL) for creatinine and -13.3 mL/min/1.73 m2 (range: -63.7 to 40.1 mL/min/1.73 m2) for eGFR observed after 96 weeks of therapy. In subjects with mild or moderate baseline renal dysfunction, the serum creatinine increase observed was similar to that seen in subjects with normal renal function. These changes were not considered clinically relevant and no subject discontinued therapy due to increases in serum creatinine.

Proximal renal tubulopathy generally resolved or improved after tenofovir DF was stopped; however, decreased CrCl did not completely resolve in some patients after stopping the drug. Rhabdomyolysis, osteomalacia, bone abnormalities (infrequently contributing to fractures), hypokalemia, muscular weakness, myopathy, and hypophosphatemia have occurred as a result of proximal renal tubulopathy.^[Ref]

Dermatologic

Emtricitabine/rilpivirine/tenofovir DF:

-Postmarketing reports: Severe skin and hypersensitivity reactions (including drug reaction with eosinophilia and systemic symptoms [DRESS]), severe skin reactions with systemic symptoms (including rashes with fever, blisters, conjunctivitis, angioedema, elevated liver function tests, and/or eosinophilia)

Emtricitabine-tenofovir DF plus rilpivirine:

-Common (1% to 10%): Rash

Emtricitabine and tenofovir alafenamide:

-Common (1% to 10%): Rash

-Uncommon (0.1% to 1%): Pruritus

Emtricitabine and/or tenofovir DF:

-Very common (10% or more): Rash

-Frequency not reported: Lipodystrophy

-Postmarketing reports: Rash

Emtricitabine:

-Very common (10% or more): Rash

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

-Postmarketing reports: Angioedema

Rilpivirine:

-Very common (10% or more): Rash

-Postmarketing reports: Severe skin and hypersensitivity reactions (including DRESS)

Tenofovir alafenamide:

-Postmarketing reports: Angioedema, urticaria, rash

Tenofovir DF:

-Very common (10% or more): Rash

-Uncommon (0.1% to 1%): Angioedema

-Postmarketing reports: Angioedema, rash^[Ref]

During phase 3 trials, 1% of patients using rilpivirine with emtricitabine and tenofovir DF reported at least grade 2 therapy-related rashes; most rashes were grade 1 or 2 and developed in the first 4 to 6 weeks of therapy.

Rash has been reported in at least 10% of therapy-naive patients treated with emtricitabine and tenofovir DF.^[Ref]

Hypersensitivity

Emtricitabine/rilpivirine/tenofovir DF:

-Postmarketing reports: Severe skin and hypersensitivity reactions (including DRESS)

Emtricitabine and/or tenofovir DF:

-Postmarketing reports: Allergic reaction (including angioedema)

Emtricitabine:

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

Rilpivirine:

-Postmarketing reports: Severe skin and hypersensitivity reactions (including DRESS)

Tenofovir DF:

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

Hepatic

Emtricitabine-tenofovir DF plus rilpivirine:

-Very common (10% or more): Increased ALT (up to 19%), increased AST (up to 16%)

-Common (1% to 10%): Increased total bilirubin

Emtricitabine and tenofovir alafenamide:

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

Emtricitabine and/or tenofovir DF:

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

-Frequency not reported: Severe hepatomegaly with steatosis, severe acute exacerbations of hepatitis B

-Postmarketing reports: Autoimmune hepatitis, hepatic steatosis, hepatitis, increased liver enzymes (primarily AST, ALT, GGT), posttherapy exacerbations of hepatitis

Emtricitabine:

-Very common (10% or more): Increased transaminases (AST and/or ALT)

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

-Frequency not reported: Liver failure, liver decompensation

Rilpivirine:

-Very common (10% or more): Increased transaminases (AST and/or ALT)

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

-Frequency not reported: Cholecystitis, cholelithiasis, hepatic enzyme elevation, hepatotoxicity, drug-induced acute allergic hepatitis

Tenofovir DF:

-Very common (10% or more): Increased transaminases (AST and/or ALT)

-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), hepatic steatosis, hepatitis^[Ref]

Increased ALT (grade 1: 19%; grade 2: 5%; grade 3: 1%; grade 4: 1%), AST (grade 1: 16%; grade 2: 4%; grade 3: 2%; grade 4: 1%), and total bilirubin (grade 1: 6%; grade 2: 3%; grade 3: 1%) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

Increased ALT (greater than 5 x ULN) and AST (greater than 5 x ULN) have been reported with emtricitabine-tenofovir DF plus rilpivirine.

Increased ALT (greater than 5 x ULN) and AST (greater than 5 x ULN) have been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF.

Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HBV and HIV-1 after discontinuation of emtricitabine or tenofovir DF and were associated with liver failure and liver decompensation in some emtricitabine-treated patients.

The incidence of hepatic enzyme elevation was higher in patients receiving rilpivirine who were coinfected with hepatitis B or C than in patients without coinfection.

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

Metabolic

Emtricitabine-tenofovir DF plus rilpivirine:

-Common (1% to 10%): Hypophosphatemia

Emtricitabine and/or tenofovir DF:

-Frequency not reported: Increased or decreased serum glucose, lactic acidosis

-Postmarketing reports: Hypokalemia, hypophosphatemia, lactic acidosis

Emtricitabine:

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

Rilpivirine:

-Common (1% to 10%): Decreased appetite, hypertriglyceridemia

Tenofovir DF:

-Very common (10% or more): Hypophosphatemia

-Uncommon (0.1% to 1%): Hypokalemia

-Rare (less than 0.1%): Lactic acidosis

-Postmarketing reports: Lactic acidosis, hypokalemia, hypophosphatemia

Antiretroviral therapy:

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

Increased or decreased serum glucose (less than 40 or greater than 250 mg/dL) has been reported with emtricitabine or tenofovir DF.

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

Hypokalemia and hypophosphatemia have occurred as a result of proximal renal tubulopathy.^[Ref]

Immunologic

Emtricitabine, rilpivirine, and/or 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)

Emtricitabine and/or tenofovir DF:

-Postmarketing reports: Immune reconstitution syndrome

Emtricitabine:

-Postmarketing reports: Immune reconstitution syndrome

Rilpivirine:

-Uncommon (0.1% to 1%): Immune reactivation syndrome

Tenofovir DF:

-Postmarketing reports: Immune reconstitution syndrome

Combination antiretroviral therapy:

-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)^[Ref]

Genitourinary

Emtricitabine and tenofovir alafenamide:

-Common (1% to 10%): Increased urine RBC (hematuria)

Emtricitabine and/or tenofovir DF:

-Common (1% to 10%): Increased urine RBC (hematuria)

-Frequency not reported: Increased glycosuria

-Postmarketing reports: Proteinuria, polyuria

Tenofovir DF:

-Uncommon (0.1% to 1%): Proteinuria

-Postmarketing reports: Polyuria, proteinuria^[Ref]

Increased urine RBC (hematuria; greater than 75 RBC/high power field) has been reported with products containing emtricitabine-tenofovir alafenamide and products containing emtricitabine-tenofovir DF.

Increased glycosuria (3+ or greater) and hematuria (greater than 75 RBC/high power field) have been reported with emtricitabine or tenofovir DF.^[Ref]

Respiratory

Emtricitabine and/or tenofovir DF:

-Common (1% to 10%): Nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, increased cough, rhinitis

-Postmarketing reports: Dyspnea

Tenofovir DF:

-Postmarketing reports: Dyspnea^[Ref]

Nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, increased cough, and rhinitis have been reported in at least 5% of therapy-experienced or therapy-naive patients treated with emtricitabine or tenofovir DF.^[Ref]

Hematologic

Emtricitabine or tenofovir DF:

-Frequency not reported: Decreased neutrophils

Emtricitabine:

-Common (1% to 10%): Neutropenia

-Uncommon (0.1% to 1%): Anemia

Rilpivirine:

-Common (1% to 10%): Decreased WBC count, decreased hemoglobin, decreased platelet count^[Ref]

Decreased neutrophils (less than 750/mm3) have been reported with emtricitabine or tenofovir DF.^[Ref]

Endocrine

Rilpivirine:

-Frequency not reported: Decreased basal cortisol, decreased adrenocorticotropic hormone (ACTH)-stimulated cortisol levels, adrenal insufficiency, abnormal 250 mcg ACTH stimulation test

Tenofovir DF:

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

In the pooled phase 3 trials, at week 96, there was an overall mean change from baseline in basal cortisol of -19.1 nmol/L (-0.69 mcg/dL) in the rilpivirine group, and of -0.6 nmol/L (-0.02 mcg/dL) in the efavirenz group. At week 96, the mean change from baseline in ACTH-stimulated cortisol levels was lower in the rilpivirine group (+18.4 nmol/L) than in the efavirenz group (+54.1 nmol/L). Mean values for both basal and ACTH-stimulated cortisol values at week 96 were within the normal range.

In the rilpivirine group, 43 of 588 patients with normal 250 mcg ACTH stimulation test at baseline developed abnormal 250 mcg ACTH stimulation test (peak cortisol level less than 18.1 mcg/dL) during the trial versus 18 of 561 patients in the efavirenz group. Abnormal 250 mcg ACTH stimulation test at week 96 was seen in 14 of the 43 rilpivirine patients and 9 of the 18 efavirenz patients. Clinical significance of abnormal 250 mcg ACTH stimulation tests (or the higher rate in the rilpivirine group) has not been established.

Overall, there were no serious side effects, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency.^[Ref]