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Isentress Side Effects

Generic Name: raltegravir

Note: This document contains side effect information about raltegravir. Some of the dosage forms listed on this page may not apply to the brand name Isentress.

For the Consumer

Applies to raltegravir: oral powder for suspension, oral tablet, oral tablet chewable

Along with its needed effects, raltegravir (the active ingredient contained in Isentress) 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 raltegravir:

Less common or rare
  • Blood in the urine
  • burning or stinging of the skin
  • dark urine
  • decreased frequency or amount of urine
  • fast heartbeat
  • fever
  • general tiredness and weakness
  • hoarseness
  • increased thirst
  • irritation
  • joint pain, stiffness, or swelling
  • light-colored stools
  • loss of appetite
  • lower back or side pain
  • nausea and vomiting
  • pain in the groin or genitals
  • painful blisters on the trunk of the body
  • painful cold sores or blisters on the lips, nose, eyes, or genitals
  • rash, hives, or itching
  • redness of the skin
  • sharp back pain just below the ribs
  • swelling of the eyelids, face, lips, hands, lower legs, or feet
  • tightness in the chest
  • troubled breathing or swallowing
  • unusual tiredness or weakness
  • upper right stomach pain
  • weight gain
  • yellow eyes and skin
Incidence not known
  • Black, tarry stools
  • bleeding gums
  • headache
  • muscle cramps or spasms
  • muscle pain or stiffness
  • pinpoint red spots on the skin
  • stomach pain, continuing
  • unusual bleeding or bruising

Some side effects of raltegravir 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
  • Dizziness
  • trouble sleeping
Less common or rare
  • Belching
  • depression
  • heartburn
  • indigestion
  • lack or loss of strength
  • stomach discomfort, upset, or pain
  • tenderness in the stomach area
  • thoughts of killing oneself or changes in behavior
Incidence not known
  • Delusions of persecution, mistrust, suspiciousness, or combativeness
  • diarrhea
  • fear or nervousness

For Healthcare Professionals

Applies to raltegravir: oral granule for reconstitution, oral tablet, oral tablet chewable


The safety report of this drug is based on 281 therapy-naive and 462 therapy-experienced HIV-infected patients receiving the indicated twice daily dosing regimen in combination with emtricitabine plus tenofovir and optimized background therapy, respectively. The most common side effects of moderate to severe intensity which occurred in therapy-naive patients at a higher rate compared to efavirenz were insomnia, headache, nausea, dizziness, and fatigue. The most common side effect of moderate to severe intensity which occurred in therapy-experienced patients at a higher rate compared to placebo was headache. The rates of discontinuation due to side effects were 5% and 10% in therapy-naive subjects receiving this drug and efavirenz, respectively, and 4% and 5% in therapy-experienced subjects receiving this drug and placebo, respectively.[Ref]


Very common (10% or more): Elevated ALT (up to 11%)
Common (1% to 10%): Elevated AST, elevated total bilirubin
Uncommon (0.1% to 1%): Hepatitis, hepatic steatosis, alcoholic hepatitis, hepatic failure
Frequency not reported: AST and ALT abnormalities[Ref]

Grade 2, 3, and 4 elevations in ALT have been reported in up to 11%, up to 4.8%, and up to 2% of patients, respectively. Grade 2, 3, and 4 elevations in AST have been reported in up to 9.5%, up to 5%, and up to 1.1% of patients, respectively. Grade 2, 3, and 4 elevations in total bilirubin have been reported in up to 6%, up to 3%, and up to 1% of patients, respectively.

The rates of AST and ALT abnormalities were higher in patients with hepatitis B and/or hepatitis C virus coinfection. In therapy-naive patients, grade 2 or higher laboratory abnormalities indicating a worsening grade from baseline of AST, ALT, or total bilirubin occurred in 22%, 44%, and 17%, respectively, of coinfected patients using this drug as compared to 13%, 13%, and 5% of all other patients using this drug. In therapy-experienced patients, grade 2 or higher laboratory abnormalities indicating a worsening grade from baseline of AST, ALT, or total bilirubin occurred in 29%, 34%, and 13%, respectively, of coinfected patients using this drug as compared to 11%, 10%, and 9% of all other patients using this drug.

Hepatic failure (with and without associated hypersensitivity) has been reported during postmarketing experience in patients with underlying liver disease and/or concomitant medications.[Ref]


Very common (10% or more): Elevated serum glucose (up to 11.3%)
Common (1% to 10%): Elevated alkaline phosphatase, decreased appetite, elevated blood triglycerides
Uncommon (0.1% to 1%): Cachexia, diabetes mellitus, dyslipidemia, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperphagia, increased appetite, polydipsia, body fat disorder, decreased blood albumin, elevated blood cholesterol, elevated fasting blood glucose, elevated high-density lipoprotein, elevated low-density lipoprotein cholesterol
Frequency not reported: Elevated fasting cholesterol[Ref]

Grade 2 and 3 elevations in fasting (nonrandom) serum glucose test have been reported in up to 11.3% and up to 3% of patients, respectively. Grade 2, 3, and 4 elevations in alkaline phosphatase have been reported in up to 2.2%, less than 1%, and up to 1% of patients, respectively.[Ref]


Very common (10% or more): Diarrhea (up to 26.6%), nausea (up to 16.7%), vomiting (up to 11%)
Common (1% to 10%): Elevated lipase, elevated blood pancreatic amylase, abdominal pain, dyspepsia, abdominal distention, flatulence
Uncommon (0.1% to 1%): Gastroenteritis, gastritis, abdominal discomfort, upper abdominal pain, abdominal tenderness, anorectal discomfort, constipation, dry mouth, epigastric discomfort, erosive duodenitis, eructation, gastroesophageal reflux disease, gingivitis, glossitis, odynophagia, acute pancreatitis, peptic ulcer, rectal hemorrhage, elevated blood amylase
Frequency not reported: Mouth ulceration, peritonitis (including perihepatitis)[Ref]

Grade 2 and 3 elevations in lipase have been reported in 5% and 2% of patients, respectively. Grade 2, 3, and 4 elevations in pancreatic amylase have been reported in 2%, 4%, and less than 1% of patients, respectively.

Diarrhea has also been reported during postmarketing experience.[Ref]

Nervous system

Very common (10% or more): Central nervous system (CNS) side effects/symptoms (up to 28.8%), headache (up to 26%), dizziness (up to 16.4%)
Common (1% to 10%): Psychomotor hyperactivity, vertigo
Uncommon (0.1% to 1%): Amnesia, carpal tunnel syndrome, cognitive disorder, disturbance in attention/concentration impaired, postural dizziness, dysgeusia, hypersomnia, hypoesthesia, lethargy, memory impairment, migraine, peripheral neuropathy, paresthesia, somnolence, tension headache, tremor, poor quality sleep, tinnitus
Frequency not reported: Nervous system disorder, depressed level of consciousness
Postmarketing reports: Cerebellar ataxia[Ref]

CNS side effects were reported less often in therapy-naive patients using this drug (with emtricitabine and tenofovir) than those using efavirenz (with emtricitabine and tenofovir). By weeks 8, 48, and 96, at least 1 CNS symptom was reported in 20.3%, 26.3%, and 28.8% of patients using this drug, respectively, compared with 52.1%, 58.5%, and 60.6% of patients using efavirenz, respectively. CNS side effects included dizziness, insomnia, concentration impaired, somnolence, depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, auditory hallucination, completed suicide, and major depression.[Ref]


Very common (10% or more): Insomnia (up to 15.7%), depression (up to 10.3%)
Common (1% to 10%): Abnormal dreams, nightmare, abnormal behavior, anxiety
Uncommon (0.1% to 1%): Mental disorder, suicide attempt, confusional state, depressed mood, major depression, middle insomnia, mood altered, panic attack, sleep disorder, suicidal ideation, suicidal behavior
Frequency not reported: Exacerbation of depression, psychotic disorder, acute psychosis, delirium, hallucination, auditory hallucination, completed suicide
Postmarketing reports: Paranoia[Ref]

Depression (including suicidal ideation and behaviors) has been reported in clinical studies and during postmarketing experience, particularly in patients with history of psychiatric illness or depression.

Anxiety, suicidal ideation, and suicidal behavior (particularly in patients with history of psychiatric illness) have also been reported during postmarketing experience.[Ref]


Grade 2, 3, and 4 decreases in absolute neutrophil count have been reported in up to 4%, 3%, and 1% of patients, respectively. Grade 2, 3, and 4 decreases in platelet count have been reported in up to 3%, up to 1%, and up to 1% of patients, respectively. Grade 2, 3, and 4 decreases in hemoglobin have been reported in 1%, 1%, and less than 1% of patients, respectively.

Thrombocytopenia has also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Decreased absolute neutrophil count, decreased platelet count, decreased hemoglobin, atypical lymphocytes
Uncommon (0.1% to 1%): Anemia, iron deficiency anemia, lymph node abscess, lymph node pain, lymphadenopathy, neutropenia, thrombocytopenia, elevated INR, decreased WBC count[Ref]


Very common (10% or more): Pyrexia (up to 15.7%), fatigue (up to 12.1%)
Common (1% to 10%): Asthenia
Uncommon (0.1% to 1%): Herpes virus infection, hot flush, menopausal symptoms, chest discomfort, chills, face edema, increased fat tissue, feeling jittery, malaise, submandibular mass, peripheral edema, pain, increased waist circumference, increased weight, accidental overdose
Frequency not reported: Decreased weight[Ref]


Grade 2, 3, and 4 elevations in creatine phosphokinase have been reported in 2.6%, 4.1%, and 3% of patients, respectively.

Rhabdomyolysis has also been reported during postmarketing experience.[Ref]

Very common (10% or more): Back pain (up to 12.1%)
Common (1% to 10%): Elevated creatine phosphokinase, arthralgia
Uncommon (0.1% to 1%): Arthritis, flank pain, musculoskeletal pain, myalgia, neck pain, osteopenia, pain in extremity, tendonitis, rhabdomyolysis
Frequency not reported: Myopathy, osteonecrosis, osteoporosis, polyarthritis[Ref]


Uncommon (0.1% to 1%): Palpitations, sinus bradycardia, ventricular extrasystoles, hypertension
Frequency not reported: Myocardial infarction[Ref]


Uncommon (0.1% to 1%): Nephrolithiasis, renal failure, nephritis, renal cyst, renal impairment, tubulointerstitial nephritis, elevated blood creatinine, elevated BUN
Frequency not reported: Toxic nephropathy, chronic renal failure, renal tubular necrosis[Ref]


Common (1% to 10%): Hypersensitivity (less than 2%)
Uncommon (0.1% to 1%): Drug hypersensitivity
Frequency not reported: Hypersensitivity reactions (characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure)[Ref]


Rashes considered drug related were mild to moderate in severity and did not limit treatment. In clinical trials of therapy-experienced patients, rash occurred more often with regimens containing this drug and darunavir compared to those containing this drug without darunavir or darunavir without this drug.

Severe, potentially life-threatening, and fatal skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported.

Stevens-Johnson syndrome and DRESS have also been reported during postmarketing experience.[Ref]

Common (1% to 10%): Rash
Uncommon (0.1% to 1%): Pruritus, acne, alopecia, dermatitis acneiform, dry skin, erythema, facial wasting, hyperhidrosis, lipoatrophy, acquired lipodystrophy, lipohypertrophy, night sweats, prurigo, generalized pruritus, macular rash, maculopapular rash, pruritic rash, skin lesion, urticaria, xeroderma, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), folliculitis, herpes simplex, herpes zoster, molluscum contagiosum
Frequency not reported: Severe skin reactions, toxic epidermal necrolysis, diaphoresis[Ref]


Uncommon (0.1% to 1%): Skin papilloma
Frequency not reported: Kaposi's sarcoma, lymphoma, squamous cell carcinoma, skin cancer, hepatocellular carcinoma, rectal adenocarcinoma, anal cancer[Ref]

The types and rates of specified cancers were expected in a highly immunodeficient population and most patients had other risk factors for cancer, including tobacco use, papillomavirus, and active hepatitis B virus infection. It is unknown if these cancer diagnoses were related to use of this drug.[Ref]


Uncommon (0.1% to 1%): Immune reconstitution syndrome
Frequency not reported: Autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)[Ref]


Uncommon (0.1% to 1%): Gynecomastia


Uncommon (0.1% to 1%): Genital herpes, nocturia, erectile dysfunction, glucose present in urine, positive for RBCs in urine[Ref]


Uncommon (0.1% to 1%): Visual impairment[Ref]


Very common (10% or more): Nasopharyngitis (up to 26.7%), upper respiratory tract infection (up to 21.4%), cough (up to 16.7%), influenza (up to 11.7%)
Uncommon (0.1% to 1%): Dysphonia, epistaxis, nasal congestion[Ref]


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Some side effects of Isentress may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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