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Isentress Side Effects

Generic Name: raltegravir

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

For the Consumer

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

In addition to its needed effects, some unwanted effects may be caused by raltegravir (the active ingredient contained in Isentress). In the event that any of these side effects do occur, they may require medical attention.

Severity: Major

You should check with your doctor immediately if any of these side effects occur when 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 abdominal or 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

Severity: Minor

Some of the side effects that can occur with raltegravir may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common:
  • Dizziness
  • trouble sleeping
Less common or rare:
  • Acid or sour stomach
  • 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 raltegravir (the active ingredient contained in Isentress) is based on 281 treatment-naive and 462 treatment-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 treatment-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 treatment-experienced patients at a higher rate compared to placebo was headache. The rates of discontinuation due to side effects were 5% and 10% in treatment-naive subjects receiving raltegravir and efavirenz, respectively, and 4% and 5% in treatment-experienced subjects receiving raltegravir and placebo, respectively.[Ref]


Common (1% to 10%): Elevated alanine transaminase (ALT; Grade 2: up to 11%, Grade 3: up to 4%, Grade 4: up to 2%), elevated aspartate transaminase (AST; Grade 2: up to 9%, Grade 3: up to 5%, Grade 4: 1%), elevated total bilirubin (Grade 2: up to 6%, Grade 3: up to 3%), hepatitis (less than 2%)
Uncommon (0.1% to 1%): Elevated total bilirubin (Grade 4: up to 1%)
Frequency not reported: AST and ALT abnormalities
Postmarketing reports: Hepatic failure (with and without associated hypersensitivity)[Ref]

The rates of AST and ALT abnormalities were higher in patients with hepatitis B and/or hepatitis C virus coinfection. In treatment-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 treated with raltegravir as compared to 13%, 13%, and 5% of all other patients treated with raltegravir. In treatment-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 treated with raltegravir as compared to 11%, 10%, and 9% of all other patients treated with raltegravir.

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


Common (1% to 10%): Elevated serum glucose (Grade 2: up to 10%, Grade 3: up to 3%), elevated alkaline phosphatase (Grade 2: up to 2%)
Uncommon (0.1% to 1%): Elevated alkaline phosphatase (Grade 3: less than 1%, Grade 4: up to 1%)
Frequency not reported: Acquired lipodystrophy, elevated triglycerides, elevated fasting cholesterol, elevated low density lipoprotein cholesterol[Ref]


Common (1% to 10%): Elevated lipase (Grade 2: 5%, Grade 3: 2%), nausea (moderate to severe intensity: 3%), elevated pancreatic amylase (Grade 2: 2%, Grade 3: 4%), abdominal pain (less than 2%), gastritis (less than 2%), dyspepsia (less than 2%), vomiting (less than 2%)
Uncommon (0.1% to 1%): Elevated pancreatic amylase (Grade 4: less than 1%)
Rare (less than 0.1%): Mouth ulceration (at least 1 case), peritonitis (including perihepatitis; at least 1 case)
Postmarketing reports: Diarrhea[Ref]

Nervous system

Common (1% to 10%): Headache (moderate to severe intensity: up to 4%), dizziness (moderate to severe intensity: 2%)
Postmarketing reports: Cerebellar ataxia[Ref]


Common (1% to 10%): Insomnia (moderate to severe intensity: 4%), depression (including suicidal ideation and behaviors; less than 2%)
Frequency not reported: Abnormal dreams, exacerbation of depression
Postmarketing reports: Anxiety, paranoia[Ref]

Depression occurred particularly in patients with history of psychiatric illness.[Ref]


Common (1% to 10%): Decreased absolute neutrophil count (Grade 2: up to 4%, Grade 3: 3%, Grade 4: 1%), decreased platelet count (Grade 2: up to 3%), decreased hemoglobin (Grade 2: 1%, Grade 3: 1%)
Uncommon (0.1% to 1%): Decreased platelet count (Grade 3: up to 1%, Grade 4: up to 1%), decreased hemoglobin (Grade 4: less than 1%)
Postmarketing reports: Thrombocytopenia[Ref]


Common (1% to 10%): Fatigue (moderate to severe intensity: 2%), asthenia (less than 2%), genital herpes (less than 2%), herpes zoster (less than 2%)
Frequency not reported: Pyrexia, diaphoresis[Ref]


Common (1% to 10%): Elevated creatine kinase (Grade 2: 2%, Grade 3: 4%, Grade 4: 3%)
Frequency not reported: Myopathy, rhabdomyolysis
Postmarketing reports: Rhabdomyolysis[Ref]


Frequency not reported: Myocardial infarction[Ref]


Common (1% to 10%): Nephrolithiasis (less than 2%), renal failure (less than 2%)
Frequency not reported: Toxic nephropathy, chronic renal failure, renal tubular necrosis[Ref]


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


Frequency not reported: Skin rash; pruritus; severe, potentially life-threatening, and fatal skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis)[Ref]

Rashes considered drug related were mild to moderate in severity and did not limit treatment.[Ref]


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 raltegravir use.[Ref]


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


1. The Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children Francois-Xavier Bagnoud Center, UMDNJ, The Health Resources and Services Administration, The National Institutes of Health "Guidelines for the use of antiretroviral agents in pediatric HIV infection. Available from: URL:" ([2008 Feb 28]):

2. "Two new drugs for HIV infection." Med Lett Drugs Ther 50 (2008): 2-4

3. Cocohoba J, Dong BJ "Raltegravir: The first HIV integrase inhibitor." Clin Ther 30 (2008): 1747-65

4. Croxtall JD, Keam SJ "Raltegravir: A Review of its Use in the Management of HIV Infection in Treatment-Experienced Patients." Drugs 69 (2009): 1059-75

5. "Drugs for HIV infection." Treat Guidel Med Lett 7 (2009): 11-22

6. Iwamoto M, Wenning LA, Petry AS, et al. "Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects." Mol Ther 83 (2008): 293-9

7. Panel on Antiretroviral Guidelines for Adult and Adolescents. NIH. National Institute of Health "Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available from: URL:" ([2008 Jan 29]):

8. Croxtall JD, Lyseng-Williamson KA, Perry CM "Raltegravir." Drugs 68 (2008): 131-8

9. "Product Information. Isentress (raltegravir)." Merck & Company Inc, West Point, PA.

10. Reiss KA, Bailey JR, Pham PA, Gallant JE "Raltegravir-induced cerebellar ataxia." AIDS 24 (2010): 2757

11. Madeddu G, Menzaghi B, Ricci E, et al. "Raltegravir central nervous system tolerability in clinical practice: results from a multicenter observational study." AIDS 26 (2012): 2412-5

12. Fleischbein E, O'Brien J, Martelino R, Fenstersheib M "Elevated alkaline phosphatase with raltegravir in a treatment experienced HIV patient." AIDS 22 (2008): 2404-5

13. "Anti-HIV agents. Merck integrase inhibitor." TreatmentUpdate 18 (2006): 3-4

14. Iwamoto M, Hanley WD, Petry AS, et al. "Lack of a Clinically Important Effect of Moderate Hepatic Insufficiency and Severe Renal Insufficiency on Raltegravir Pharmacokinetics." Antimicrob Agents Chemother (2009):

15. Wenning LA, Hanley WD, Brainard DM, et al. "Effect of rifampin, a potent inducer of drug metabolizing enzymes, on the pharmacokinetics of raltegravir." Antimicrob Agents Chemother 53 (2009): 2852-6

16. Harris M, Larsen G, Montaner JS "Exacerbation of depression associated with starting raltegravir: a report of four cases." AIDS 22 (2008): 1890-2

17. "Anti-HIV agents. Integrase inhibitor raltegravir makes its mark." TreatmentUpdate 19 (2007): 8-9

18. Borras-Blasco J, Navarro-Ruiz A, Borras C, Castera E "Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection." J Antimicrob Chemother 62 (2008): 879-88

19. Zembower TR, Gerzenshtein L, Coleman K, Palella FJ Jr "Severe rhabdomyolysis associated with raltegravir use." AIDS 22 (2008): 1382-4

20. Monteiro P, Perez I, Pich J, Gatell JM, Martinez E "Creatine kinase elevation in HIV-1-infected patients receiving raltegravir-containing antiretroviral therapy: a cohort study." J Antimicrob Chemother 68 (2013): 404-8

21. Dori L, Buonomini AR, Viscione M, Sarmati L, Andreoni M "A case of rhabdomiolysis associated with raltegravir use." AIDS 24 (2010): 473-5

22. Vassallo M, Dunais B, Naqvi A, Garaffo R, Durant J "Raltegravir-induced nephrolithiasis: a case report." AIDS 26 (2012): 1323-4

Not all side effects for Isentress may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.