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

Serious side effects of Raltegravir

Along with its needed effects, raltegravir 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
• hoarseness
• increased thirst
• irritation
• joint pain, stiffness, or swelling
• light-colored stools
• loss of appetite
• lower back or side pain
• nausea
• 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
• trouble breathing or swallowing
• unusual tiredness or weakness
• upper right stomach pain
• vomiting
• weight gain
• yellow eyes and skin

Incidence not known

• Black, tarry stools
• bleeding gums
• headache
• muscle cramps, spasms, pain, or stiffness
• pinpoint red spots on the skin
• stomach pain, continuing
• unusual bleeding or bruising

Other side effects of Raltegravir

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 tenderness
• 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.

General

The most common side effects of moderate to severe intensity were insomnia, headache, nausea, dizziness, and fatigue. The most commonly reported side effects of all intensities and regardless of causality included diarrhea, nausea, headache, nasopharyngitis, fatigue, upper respiratory tract infection, pyrexia, abdominal pain, and vomiting. 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]

Hepatic

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 using 400 mg twice a day, 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 using 400 mg twice a day, 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. At 96 weeks, in therapy-naive patients using 1200 mg (as two 600 mg tablets) once a day, grade 2 or higher laboratory abnormalities indicating a worsening grade from baseline of AST, ALT, or total bilirubin occurred in 27%, 40%, and 13%, respectively, of coinfected patients treated with 1200 mg once a day as compared to 7%, 5%, and 3% of all other patients treated with 1200 mg once a day.

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

Metabolic

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.^[Ref]

Very common (10% or more): Elevated serum glucose (up to 11.3%)

Common (1% to 10%): 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]

Gastrointestinal

Grade 2, 3, and 4 elevations in lipase have been reported in up to 7%, up to 2%, and up to 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]

Very common (10% or more): Diarrhea (up to 26.6%), nausea (up to 16.7%)

Common (1% to 10%): Vomiting, 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]

Nervous system

CNS side effects were reported less often in therapy-naive patients using this drug (with emtricitabine and tenofovir disoproxil fumarate [DF]) than those using efavirenz (with emtricitabine and tenofovir DF). 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): 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]

Psychiatric

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]

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]

Hematologic

Grade 2, 3, and 4 decreases in absolute neutrophil count have been reported in up to 4%, up to 3%, and up to 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 up to 1%, up to 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]

Other

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): Pyrexia (up to 15.7%), fatigue (up to 12.1%)

Common (1% to 10%): Asthenia, elevated alkaline phosphatase

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]

Musculoskeletal

Grade 2, 3, and 4 elevations in creatine phosphokinase have been reported in up to 5%, up to 4.1%, and up to 3.4% 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]

Cardiovascular

Uncommon (0.1% to 1%): Palpitations, sinus bradycardia, ventricular extrasystoles, hypertension

Frequency not reported: Myocardial infarction^[Ref]

Renal

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]

Hypersensitivity

Common (1% to 10%): Hypersensitivity

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]

Dermatologic

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]

Oncologic

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]

Immunologic

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, autoimmune hepatitis)^[Ref]

Endocrine

Uncommon (0.1% to 1%): Gynecomastia

Genitourinary

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

Ocular

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

Respiratory

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]