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

Serious side effects

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

Less common

• Stomach pain

Rare

• Changes in behavior
• thoughts or attempts of killing oneself

Incidence not known

• Blistering, peeling, or loosening of the skin
• bloody or cloudy urine
• chills
• confusion
• cough
• dark urine
• decreased appetite
• decreased frequency or amount of urine
• diarrhea
• difficult or painful urination
• fast, shallow breathing
• general feeling of discomfort
• hives or welts, itching, skin rash
• increased blood pressure
• increased thirst
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• loss of appetite
• lower back or side pain
• muscle pain or cramps
• nausea
• rapid weight gain
• red irritated eyes
• red skin lesions, often with a purple center
• right upper abdominal or stomach pain and fullness
• sleepiness
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• stomach discomfort
• sudden decrease in the amount of urine
• swelling of the face, fingers, or lower legs
• trouble breathing
• unusual tiredness or weakness
• vomiting
• weight gain
• yellow eyes and skin

Other side effects

Some side effects of bictegravir / emtricitabine / 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:

Less common

• Abnormal dreams
• belching
• bloated feeling
• discouragement
• dizziness
• excess air or gas in the stomach or bowels
• feeling of fullness
• feeling sad or empty
• headache
• heartburn
• indigestion
• irritability
• loss of interest or pleasure
• passing gas
• stomach upset
• trouble concentrating
• trouble sleeping

For Healthcare Professionals

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

General

In clinical trials, the most common side effects reported were diarrhea, nausea, and headache. This drug was discontinued due to side effects in 1% of patients.^[Ref]

Hepatic

Elevated total bilirubin was reported in 17% of patients through week 144; grade 1 (1 to 1.5 times the upper limit of normal [1 to 1.5 x ULN]) and grade 2 (1.5 to 2.5 x ULN) increases were reported in 12% and 4% of patients, respectively. These increases were not associated with hepatic side effects or other liver-related laboratory abnormalities. Grade 3 bilirubin increases (not considered related to study drug) were reported in 5 patients using this drug (1%). No discontinuations due to hepatic side effects were reported through week 144 in clinical studies.

Elevated AST (greater than 5 x ULN) and ALT (greater than 5 x ULN) have been reported in up to 3% and up to 2% of patients, respectively.

Out of 16 patients coinfected with HIV-1 and hepatitis B virus (HBV), hepatic flare (ALT greater than 10 x ULN) was reported in 1 patient; ALT returned to normal limits without interrupting therapy.

Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients coinfected with HIV-1 and HBV after discontinuation of products containing emtricitabine and/or tenofovir DF.

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

Very common (10% or more): Elevated total bilirubin (up to 15%)

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

Uncommon (0.1% to 1%): Hyperbilirubinemia

Frequency not reported: Hepatic flare

Emtricitabine and/or tenofovir disoproxil fumarate (DF):

-Frequency not reported: Severe hepatomegaly with steatosis, severe acute exacerbations of hepatitis B, liver decompensation, liver failure^[Ref]

Gastrointestinal

Elevated amylase (greater than 2 x ULN) was reported in 2% of patients.^[Ref]

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

Uncommon (0.1% to 1%): Vomiting, flatulence, dyspepsia, abdominal pain

Frequency not reported: Abdominal discomfort

Emtricitabine plus tenofovir alafenamide (with cobicistat and elvitegravir as a fixed-dose combination tablet):

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

Nervous system

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

Musculoskeletal

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

Uncommon (0.1% to 1%): Arthralgia

Frequency not reported: Osteonecrosis

Emtricitabine plus tenofovir alafenamide (with cobicistat and elvitegravir as a fixed-dose combination tablet):

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

Elevated creatine kinase (at least 10 x ULN) has been reported in up to 6% of patients.^[Ref]

Psychiatric

Suicidal ideation, suicide attempt, and suicidal depression were reported in less than 1% of patients; all events were serious and observed primarily in patients with history of depression, prior suicide attempt, or psychiatric illness.^[Ref]

Common (1% to 10%): Abnormal dreams, insomnia, depression

Uncommon (0.1% to 1%): Suicidal ideation, suicide attempt, anxiety, sleep disorders

Frequency not reported: Suicidal depression

Bictegravir, emtricitabine, and/or tenofovir alafenamide:

-Postmarketing reports: Suicidal behavior, anxiety, sleep disorder, depression^[Ref]

Other

Common (1% to 10%): Fatigue, elevated low-density lipoprotein (LDL) cholesterol (fasted)

Antiretroviral therapy:

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

Elevated LDL cholesterol (fasted) (greater than 190 mg/dL) has been reported in up to 3% of patients.^[Ref]

Hematologic

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

Common (1% to 10%): Decreased neutrophils

Emtricitabine:

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

Renal

Common (1% to 10%): Elevated serum creatinine

Bictegravir / emtricitabine / tenofovir alafenamide or tenofovir alafenamide-containing products:

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

Tenofovir prodrugs:

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

Increased serum creatinine occurred with bictegravir due to inhibition of tubular secretion of creatinine without affecting renal glomerular function. Increased serum creatinine was reported by 4 weeks of therapy and remained stable through 144 weeks; serum creatinine increased by 0.11 mg/dL from baseline to week 144. No discontinuations due to renal side effects were reported through week 144 in patients using this drug in clinical studies; renal serious side effects occurred in less than 1% of patients using this drug through week 48 in clinical trials.

Renal impairment (including cases of acute renal failure and Fanconi syndrome) has been reported with the use of tenofovir prodrugs; no cases of Fanconi syndrome or proximal renal tubulopathy were reported in clinical trials of this drug.^[Ref]

Dermatologic

Uncommon (0.1% to 1%): Rash, pruritus

Postmarketing reports: Stevens-Johnson syndrome

Bictegravir / emtricitabine / tenofovir alafenamide or tenofovir alafenamide-containing products:

-Postmarketing reports: Angioedema, Stevens-Johnson syndrome/toxic epidermal necrolysis, urticaria

Bictegravir, emtricitabine, and/or tenofovir alafenamide:

-Postmarketing reports: Angioedema, Stevens-Johnson syndrome, urticaria

Emtricitabine- and tenofovir alafenamide-containing products:

-Postmarketing reports: Angioedema

Tenofovir alafenamide-containing products:

-Postmarketing reports: Urticaria^[Ref]

Metabolic

Emtricitabine plus tenofovir alafenamide (with cobicistat and elvitegravir as a fixed-dose combination tablet):

-Very common (10% or more): Hyperkalemia

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

Emtricitabine and tenofovir DF:

-Frequency not reported: Lactic acidosis

Antiretroviral therapy:

-Frequency not reported: Increased glucose^[Ref]

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

Immunologic

Bictegravir, emtricitabine, and/or tenofovir alafenamide:

-Postmarketing reports: Autoimmune hepatitis

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]

Respiratory

Emtricitabine plus tenofovir alafenamide (with cobicistat and elvitegravir as a fixed-dose combination tablet):

-Very common (10% or more): Pneumonia