Applies to dolutegravir / rilpivirine: oral tablet.
Serious side effects
Along with its needed effects, dolutegravir/rilpivirine 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 / rilpivirine:
Less common
- Abnormal dreams
- anxiety
- cloudy or bloody urine
- dark urine
- decreased frequency or amount of urine
- depressed mood
- gaseous stomach pain
- increased blood pressure
- increased thirst
- indigestion
- light-colored stools
- loss of appetite
- lower back or side pain
- nausea
- recurrent fever
- severe nausea or vomiting
- stomach fullness or pain
- swelling of the face, fingers, feet, or lower legs
- thoughts or attempts at killing oneself
- trouble sleeping
- trouble breathing
- unusual tiredness or weakness
- upper right abdominal or stomach pain
- vomiting
- weight gain
- yellow eyes or skin
Incidence not known
- Black, tarry stools
- chest pain
- chills
- cough
- decreased appetite
- difficulty swallowing
- fast heartbeat
- fever
- headache
- painful or difficult urination
- skin itching, rash, or redness
- sore throat
- sores, ulcers, or white spots on the lips or in the mouth
- stomach tenderness
- stomach pain, continuing
- swelling of the face, throat, or tongue
- swollen glands
- unusual bleeding or bruising
Other side effects
Some side effects of dolutegravir / rilpivirine 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
- Bloated feeling
- diarrhea
- dizziness
- excess air or gas in the stomach or bowels
- feeling of fullness
- muscle pain
- passing gas
- sleepiness or unusual drowsiness
Incidence not known
- Difficulty in moving
- joint pain or swelling
- muscle ache, cramp, or stiffness
For Healthcare Professionals
Applies to dolutegravir / rilpivirine: oral tablet.
General
In clinical trials, dolutegravir plus rilpivirine was discontinued due to side effects in 4% of patients. The most common side effects leading to discontinuation were psychiatric disorders.[Ref]
Nervous system
Very common (10% or more): Headache, dizziness
Common (1% to 10%): Somnolence
Dolutegravir:
-Very common (10% or more): Headache
-Common (1% to 10%): Dizziness
Rilpivirine:
-Common (1% to 10%): Headache, dizziness
-Uncommon (0.1% to 1%): Somnolence[Ref]
Gastrointestinal
Very common (10% or more): Nausea, increased pancreatic amylase, diarrhea
Common (1% to 10%): Abdominal pain, vomiting, elevated lipase, gastroenteritis, dyspepsia, upper abdominal pain, constipation, flatulence, abdominal distention, abdominal discomfort, dry mouth
Dolutegravir:
-Very common (10% or more): Nausea, diarrhea
-Common (1% to 10%): Abdominal pain, vomiting, flatulence, upper abdominal pain, abdominal discomfort
Rilpivirine:
-Common (1% to 10%): Abdominal pain, nausea, vomiting
-Uncommon (0.1% to 1%): Abdominal discomfort[Ref]
Grade 2 and grade 3 to 4 elevations in lipase were reported in 5% and 2% of patients, respectively.[Ref]
Other
Very common (10% or more): Increased fasted total cholesterol, increased fasted low-density lipoprotein cholesterol
Common (1% to 10%): Fatigue, asthenia, syphilis, increased fasted triglycerides
Dolutegravir:
-Common (1% to 10%): Fatigue
-Postmarketing reports: Increased weight
Rilpivirine:
-Common (1% to 10%): Fatigue[Ref]
Psychiatric
Very common (10% or more): Insomnia
Common (1% to 10%): Depression, abnormal dreams, sleep disorders, depressed mood, anxiety
Uncommon (0.1% to 1%): Suicidal ideation, suicide attempt
Frequency not reported: Depressive disorders (including depressed mood, depression, suicidal ideation/attempt/behavior/completion)
Dolutegravir:
-Common (1% to 10%): Insomnia, abnormal dreams, depression, anxiety
-Uncommon (0.1% to 1%): Suicidal ideation, suicide attempt
Rilpivirine:
-Common (1% to 10%): Depression, insomnia, abnormal dreams, sleep disorders
-Uncommon (0.1% to 1%): Depressed mood[Ref]
Suicidal ideation or suicide attempt was reported, mainly in patients with history of depression or psychiatric illness.
Depressive disorders occurred primarily in patients with history of depression or other psychiatric illness.[Ref]
Hepatic
Grade 2 and grade 3 to 4 elevations in ALT were reported in 2% and less than 1% of patients, respectively. Grade 2 elevations in total bilirubin were reported in 2% of patients. Grade 2 and grade 3 to 4 elevations in AST were each reported in less than 1% of patients.
The incidence of liver chemistry elevations was higher in patients coinfected with hepatitis C than in those who were not coinfected.
In some patients using dolutegravir-containing regimens, elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, especially when antihepatitis therapy was stopped.[Ref]
Very common (10% or more): Increased transaminases (elevated ALT and/or AST)
Common (1% to 10%): Elevated ALT, elevated total bilirubin
Uncommon (0.1% to 1%): Hepatitis
Frequency not reported: Cholecystitis, cholelithiasis, elevated AST, hepatic toxicity, elevated serum liver biochemistries, liver chemistry elevations
Dolutegravir:
-Uncommon (0.1% to 1%): Hepatitis
-Frequency not reported: Elevations in transaminases (consistent with immune reconstitution syndrome or hepatitis B reactivation)
-Postmarketing reports: Acute liver failure, hepatotoxicity
Rilpivirine:
-Common (1% to 10%): Increased transaminases[Ref]
Metabolic
Common (1% to 10%): Hyperglycemia, decreased appetite
Rilpivirine:
-Common (1% to 10%): Decreased appetite[Ref]
Grade 2 and grade 3 to 4 hyperglycemia were reported in 4% and less than 1% of patients, respectively.[Ref]
Musculoskeletal
Common (1% to 10%): Elevated creatine phosphokinase, decreased bone mineral density (BMD), arthralgia, back pain, pain in extremity
Uncommon (0.1% to 1%): Fractures (excluding fingers and toes), myalgia
Frequency not reported: Myositis, increased BMD, asymptomatic elevated creatine phosphokinase
Dolutegravir:
-Postmarketing reports: Arthralgia, myalgia[Ref]
BMD increased (total hip and lumbar spine) from baseline to week 48 in patients who switched from a tenofovir disoproxil fumarate (DF)-containing antiretroviral regimen to dolutegravir plus rilpivirine compared with patients who continued using a tenofovir DF-containing antiretroviral regimen. BMD declines of at least 5% at the lumbar spine were reported in 2% of patients using this drug and 5% of patients who continued using a tenofovir DF-containing antiretroviral regimen. The long-term clinical relevance of such BMD changes has not been established.
Grade 2 and grade 3 to 4 elevations in creatine phosphokinase were reported in less than 1% and 1% of patients, respectively.
Elevated creatine phosphokinase was reported, primarily associated with exercise.[Ref]
Dermatologic
Common (1% to 10%): Rash, pruritus
Dolutegravir:
-Common (1% to 10%): Rash, pruritus
Rilpivirine:
-Common (1% to 10%): Rash
-Postmarketing reports: Severe skin and hypersensitivity reactions (including drug reaction with eosinophilia and systemic symptoms [DRESS])[Ref]
Grade 2 to 3 therapy-related rashes were reported in 3% of patients during phase 3 trials of rilpivirine.[Ref]
Respiratory
Common (1% to 10%): Nasopharyngitis, upper respiratory tract infection, bronchitis, sinusitis, influenza
Hematologic
Common (1% to 10%): Decreased WBC count, decreased hemoglobin, decreased platelet count
Hypersensitivity
Uncommon (0.1% to 1%): Hypersensitivity
Dolutegravir:
-Uncommon (0.1% to 1%): Hypersensitivity reactions (characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury)[Ref]
Renal
Frequency not reported: Membranous glomerulonephritis, mesangioproliferative glomerulonephritis, nephrolithiasis, renal impairment, increased serum creatinine
Rilpivirine:
-Postmarketing reports: Nephrotic syndrome[Ref]
Both components of this drug have increased serum creatinine due to inhibition of tubular secretion of creatinine without affecting renal glomerular function. Increased serum creatinine was reported within the first 4 weeks of therapy and remained stable through 48 weeks. A mean change from baseline of 0.093 mg/dL (range: -0.3 to 0.58 mg/dL) or 8.22 mcmol/L (range: -26.5 to 51.2 mcmol/L) was reported after 48 weeks of therapy; these changes were not considered clinically significant.[Ref]
Immunologic
Frequency not reported: Immune reconstitution syndrome
Dolutegravir:
-Uncommon (0.1% to 1%): 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]
Endocrine
Rilpivirine:
-Frequency not reported: Decreased basal cortisol, abnormal 250 mcg adrenocorticotropic hormone (ACTH) stimulation test, adrenal insufficiency[Ref]
In the pooled phase 3 trials, at week 96, there was an overall mean change from baseline in basal cortisol of -0.69 mcg/dL in the rilpivirine group, and of -0.02 mcg/dL in the efavirenz group.
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. Overall, there were no serious side effects, deaths, or treatment discontinuations that could clearly be attributed to adrenal insufficiency. Clinical significance of abnormal 250 mcg ACTH stimulation tests in the rilpivirine group has not been established.[Ref]
