Applies to dolutegravir: oral tablet, oral tablet for suspension.

Serious side effects of Dolutegravir

Along with its needed effects, dolutegravir 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 dolutegravir:

Less common

• Black, tarry stools
• blistering or peeling skin
• bloody urine
• burning, dry, or itching eyes
• chest pain
• chills
• cough
• dark urine
• decreased frequency or amount of urine
• discharge or excessive tearing
• fever
• general feeling of discomfort or illness
• increased thirst
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• light-colored stools
• loss of appetite
• lower back or side pain
• muscle or joint aches
• nausea
• painful or difficult urination
• rash with fever
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• severe rash
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swelling of the face, fingers, feet, or lower legs
• swollen glands
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• upper right abdominal or stomach pain
• vomiting
• weight gain
• yellow eyes and skin

Incidence not known

• Clay-colored stools
• decreased appetite
• headache
• stomach pain or tenderness

Other side effects of Dolutegravir

Some side effects of dolutegravir 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

• Itching skin
• stomach discomfort
• trouble sleeping

Rare

• Abnormal dreams
• diarrhea
• dizziness

Incidence not known

• Anxiety
• difficulty in moving
• joint pain or swelling
• muscle cramp or stiffness

For Healthcare Professionals

Applies to dolutegravir: oral tablet, oral tablet dispersible.

General

The most common side effects were diarrhea, nausea, and headache. The most common side effects of moderate to severe intensity were insomnia, fatigue, and headache.^[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (up to 18%), nausea (up to 13%), elevated lipase

Common (1% to 10%): Abdominal pain, abdominal discomfort, flatulence, upper abdominal pain, vomiting^[Ref]

Grade 2 and grade 3 to 4 elevations in lipase were reported in up to 11% and up to 5% of therapy-naive patients, respectively. Elevated lipase was reported in 10% of therapy-experienced integrase strand transfer inhibitor (INSTI)-experienced patients.^[Ref]

Nervous system

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

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

Hepatic

Grade 2 and grade 3 to 4 elevations in AST were reported in up to 5% and up to 3% of therapy-naive patients, respectively. Grade 2 and grade 3 to 4 elevations in ALT were reported in 4% and up to 2% of therapy-naive patients, respectively. Grade 2 and grade 3 to 4 elevations in total bilirubin were reported in up to 3% and less than 1% of therapy-naive patients, respectively. Elevated ALT and AST were reported in 9% and 8% of therapy-experienced INSTI-experienced patients, respectively.

The rates of AST and ALT abnormalities were higher patients coinfected with hepatitis B and/or C virus. ALT abnormalities (grade 2 to 4) in hepatitis B and/or C coinfected patients compared with HIV monoinfected patients were reported in 18% versus 3% with 50 mg once a day and 13% versus 8% with 50 mg twice a day.

Liver chemistry elevations consistent with immune reconstitution syndrome were reported in some patients with hepatitis B and/or C at the start of therapy, especially when antihepatitis therapy was stopped.

Acute liver failure has been reported in a regimen containing this drug; contribution of this drug was unclear.^[Ref]

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

Uncommon (0.1% to 1%): Hepatitis

Rare (0.01% to 0.1%): Increased bilirubin (in combination with increased transaminases)

Frequency not reported: Liver chemistry elevations consistent with immune reconstitution syndrome

Postmarketing reports: Acute liver failure, hepatotoxicity^[Ref]

Metabolic

Common (1% to 10%): Hyperglycemia

Frequency not reported: Fasted lipid values increased (including cholesterol, HDL cholesterol, LDL cholesterol, triglycerides)

Antiretroviral therapy:

-Frequency not reported: Increased glucose levels^[Ref]

Grade 2 and grade 3 hyperglycemia were reported in up to 9% and up to 2% of therapy-naive patients, respectively. Hyperglycemia and elevated cholesterol were reported in 14% and 10% of therapy-experienced INSTI-experienced patients, respectively.^[Ref]

Psychiatric

Suicidal ideation, attempt, behavior, or completion were observed primarily in patients with history of depression or other psychiatric illness.^[Ref]

Common (1% to 10%): Insomnia, abnormal dreams, depression

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

Frequency not reported: Suicidal behavior, suicide completion

Postmarketing reports: Anxiety^[Ref]

Musculoskeletal

Grade 2 and grade 3 to 4 elevations in CPK were reported in up to 5% and up to 7% of therapy-naive patients, respectively. Elevated CPK was reported in 6% of therapy-experienced INSTI-experienced patients.

Arthralgia and myalgia have also been reported during postmarketing experience.^[Ref]

Common (1% to 10%): Elevated creatine phosphokinase (CPK)

Uncommon (0.1% to 1%): Arthralgia, myalgia

Frequency not reported: Myositis^[Ref]

Hematologic

Grade 2 and grade 3 to 4 reductions in total neutrophils were reported in up to 4% and up to 3% of therapy-naive patients, respectively. Hematology laboratory abnormality (grade 3 to 4) was reported in 2% of therapy-experienced INSTI-experienced patients, with neutropenia (2%) reported most often.^[Ref]

Common (1% to 10%): Decreased total neutrophils, hematology laboratory abnormality

Frequency not reported: Decreased neutrophil count, decreased hemoglobin^[Ref]

Dermatologic

Common (1% to 10%): Pruritus, rash (includes rash, generalized rash, macular rash, maculopapular rash, pruritic rash, drug eruption)^[Ref]

Renal

Frequency not reported: Renal impairment, increased serum creatinine (due to inhibition of tubular secretion of creatinine), changes in median serum creatinine^[Ref]

Increased serum creatinine occurred due to inhibition of tubular secretion of creatinine without affecting renal glomerular function. Increased serum creatinine was reported within the first week of therapy and remained stable through 48 weeks; a mean change of 9.96 mcmol/L (range of -53 to 54.8 mcmol/L) was reported after 48 weeks of therapy in therapy-naive patients. Increased serum creatinine was reported within the first 4 weeks of therapy and remained stable through 96 weeks; a mean change of 0.15 mg/dL (range of -0.32 to 0.65 mg/dL) was reported after 96 weeks of therapy in therapy-naive patients.^[Ref]

Other

Common (1% to 10%): Fatigue

Frequency not reported: Decreased blood bicarbonate, increased blood potassium

Postmarketing reports: Increased weight

Antiretroviral therapy:

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

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity reactions (characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury)^[Ref]

Immunologic

Uncommon (0.1% to 1%): Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome, autoimmune hepatitis)

Frequency not reported: Immune reconstitution inflammatory syndrome^[Ref]