Applies to ipilimumab: parenteral injection concentrate.

Side effects include:

Fatigue, diarrhea, pruritus, rash, colitis.

For Healthcare Professionals

Applies to ipilimumab: intravenous solution.

General

The most common adverse reactions reported with this drug as a single agent were fatigue, diarrhea, pruritus, rash, decreased appetite, nausea, vomiting, abdominal pain, cough, headache, pyrexia, insomnia, weight loss, and colitis.

The most common adverse reactions reported with this drug in combination with nivolumab were fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, increased transaminases, hypothyroidism, constipation, decreased weight, and dizziness.

The most common adverse reactions with this drug in combination with nivolumab and platinum-doublet chemotherapy were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.^[Ref]

Cardiovascular

Common (1% to 10%): Hypertension (includes hypertension, increased blood pressure), hypotension, flushing, hematoma, venous thrombosis, thrombosis, hemorrhage, lymphedema, arrhythmia (including ventricular arrhythmia), atrial fibrillation, cardiac failure, hot flush, tachycardia

Uncommon (0.1% to 1%): Myocarditis, bradycardia, vasculitis, angiopathy, peripheral ischemia, orthostatic hypotension

Rare (0.01% to 0.1%): Cardiomyopathy, pericardial effusion (pericarditis), temporal arteritis, Raynaud's phenomenon

Frequency not reported: Pericarditis, acute heart failure, shock, pericardial disorders (includes pericarditis, pericardial effusion, cardiac tamponade, Dressler's syndrome)

Dermatologic

Very common (10% or more): Rash (includes pustular rash, dermatitis, acneiform dermatitis, allergic dermatitis, atopic dermatitis, bullous dermatitis, exfoliative dermatitis, psoriasiform dermatitis, drug eruption, exfoliative rash, erythematous rash, follicular rash, generalized rash, macular rash, maculopapular rash, morbilliform rash, papular rash, papulosquamous rash, pruritic rash, fixed-drug eruption, autoimmune dermatitis, contact dermatitis, granulomatous dermatitis, dyshidrotic eczema, eczema, nodular rash, rash, toxic skin eruption, acne, generalized exfoliative rash, keratoderma blenorrhagica, skin exfoliation, skin reaction, skin toxicity, Stevens-Johnson syndrome, urticaria, pemphigoid; up to 53%), pruritus (includes pruritus, generalized pruritus, allergic pruritus; up to 53%), immune-related skin adverse reactions (up to 42%), immune-mediated rash (up to 28%), dry skin (up to 11%), alopecia (up to 11%)

Common (1% to 10%): Vitiligo, urticaria, erythema, night sweats, dermatitis, eczema, skin hypopigmentation, cellulitis, contusion, excoriation

Uncommon (0.1% to 1%): Toxic epidermal necrolysis, Stevens-Johnson syndrome, psoriasis, erythema multiforme, leukocytoclastic vasculitis, skin exfoliation, hair color changes

Frequency not reported: Hypersensitivity vasculitis, palmar-plantar erythrodysesthesia syndrome, pemphigoid, erythema nodosum

Postmarketing reports: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)

Endocrine

Very common (10% or more): Increased thyroid stimulating hormone (TSH; up to 31%), immune-mediated endocrinopathies (up to 28%), hypothyroidism (includes autoimmune thyroiditis, increased blood TSH, hypothyroidism, primary hypothyroidism, thyroiditis, decreased free triiodothyronine [T3], autoimmune hypothyroidism; up to 20%), adrenal insufficiency (up to 18%), hyperthyroidism (includes decreased blood TSH, hyperthyroidism, increased free T3; up to 12%)

Common (1% to 10%): Hypophysitis, thyroiditis, decreased blood corticotrophin, hypopituitarism (including hypophysitis), immune-related endocrine adverse reactions

Uncommon (0.1% to 1%): Hypoparathyroidism, secondary adrenocortical insufficiency, hypogonadism, decreased blood cortisol, decreased blood testosterone

Rare (0.01% to 0.1%): Hyperpituitarism, autoimmune thyroiditis, decreased blood TSH, decreased thyroxine, abnormal blood prolactin

Frequency not reported: Decreased blood gonadotrophin, thyroid dysfunction

Gastrointestinal

Very common (10% or more): Diarrhea (up to 54%), nausea (up to 44%), increased lipase (up to 51%), increased amylase (up to 39%), vomiting (up to 31%), diarrhea/colitis (includes colitis, microscopic colitis, ulcerative colitis, diarrhea, enteritis, infectious enteritis, enterocolitis, infectious enterocolitis, viral enterocolitis; up to 31%), immune-mediated colitis (up to 31%), abdominal pain (includes upper abdominal pain, lower abdominal pain, abdominal discomfort, abdominal pain, abdominal tenderness, gastrointestinal pain; up to 30%), immune-related gastrointestinal adverse reactions (up to 28%), constipation (up to 21%), colitis (up to 16%), ascites (up to 14%), dry mouth (up to 12%), dyspepsia (up to 12%), dysphagia (up to 12%), stomatitis (including aphthous ulcer, mouth ulceration, mucosal inflammation; up to 11%)

Common (1% to 10%): Pancreatitis, esophageal varices hemorrhage, gastrointestinal hemorrhage, retching, gastroenteritis, oral candidiasis, large intestine perforation, gastroesophageal reflux disease, mucosal inflammation, gastritis

Uncommon (0.1% to 1%): Intestinal perforation, enterocolitis, autoimmune pancreatitis, infectious peritonitis, duodenitis, gastrointestinal perforation, peritonitis, diverticulitis, gastric ulcer, large intestinal ulcer, esophagitis, ileus

Rare (0.01% to 0.1%): Proctitis

Genitourinary

Common (1% to 10%): Urinary tract infection, hematuria

Uncommon (0.1% to 1%): Amenorrhea, noninfective cystitis

Rare (0.01% to 0.1%): Proteinuria

Hematologic

Very common (10% or more): Anemia (includes hemolytic anemia, autoimmune anemia, iron-deficiency anemia, decreased hemoglobin; up to 70%), lymphopenia (up to 53%), neutropenia (up to 43%), leukopenia (up to 40%), thrombocytopenia (up to 34%), decreased hemoglobin (up to 25%)

Common (1% to 10%): Cytopenias, eosinophilia, febrile neutropenia, lymphadenopathy

Uncommon (0.1% to 1%): Hemolytic anemia

Rare (0.01% to 0.1%): Polycythemia

Frequency not reported: Aplastic anemia, lymphocytosis

Hepatic

In patients who received this drug with nivolumab for hepatocellular carcinoma, virologic breakthrough occurred in 4 of 28 (14%) patients and 2 of 4 (50%) patients with active HBV or HCV at baseline, respectively.

Very common (10% or more): Increased ALT (up to 66%), increased AST (up to 66%), increased bilirubin (up to 55%), hepatitis C virus (HCV) virologic breakthrough (up to 50%), hepatitis (includes increased ALT, increased AST, autoimmune hepatitis, increased blood bilirubin, increased hepatic enzyme, hepatic failure, abnormal hepatic function, hepatitis, hepatitis E, hepatocellular injury, hepatotoxicity, hyperbilirubinemia, immune-mediated hepatitis, abnormal liver function test, increased liver function test, increased transaminases; up to 21%), immune-mediated hepatitis (up to 15%), hepatitis B virus (HBV) virologic breakthrough (up to 14%)

Common (1% to 10%): Abnormal hepatic function, hepatic events, infectious hepatitis, hepatic failure, hepatomegaly, jaundice, immune-related hepatic adverse reactions

Uncommon (0.1% to 1%): Autoimmune hepatitis, increased GGT

Frequency not reported: Hepatic toxicity, abnormal liver function test

Hypersensitivity

Very common (10% or more): Hypersensitivity/infusion reactions (up to 12%)

Common (1% to 10%): Hypersensitivity, contrast media allergy, seasonal allergy

Very rare (less than 0.01%): Anaphylactic reaction (shock)

Immunologic

This drug was most commonly associated with immune-related adverse reactions (i.e., adverse reactions resulting from increased/excessive immune activity). Most of these adverse reactions (including severe reactions) resolved after appropriate medical therapy was started or this drug was withdrawn; some immune-related adverse reactions were permanent (e.g., thyroid dysfunction, diabetes mellitus). Life-threatening or fatal immune-related adverse reactions that occurred with this drug (as monotherapy or in combination with nivolumab) have included colitis, intestinal perforation, hepatitis, pneumonitis, hypophysitis, adrenal insufficiency, toxic epidermal necrolysis, myocarditis, encephalitis, myasthenia gravis, and neuropathy.

Very common (10% or more): Any immune-related adverse reactions (up to 60%)

Common (1% to 10%): Positive for treatment-emergent binding antibodies against this drug, anti-drug antibodies, neutralizing antibodies against this drug

Uncommon (0.1% to 1%): Sarcoidosis, positive antinuclear antibody

Frequency not reported: Immune-related adverse reactions with fatal outcomes (includes gastrointestinal perforation, colitis, hepatic failure, toxic epidermal necrolysis, Guillain-Barre syndrome, multi-organ failure), cytokine release syndrome

Postmarketing reports: Hemophagocytic lymphohistiocytosis, graft-versus-host disease, solid organ transplant rejection

Local

Very common (10% or more): Injection site reaction (up to 50%)

Common (1% to 10%): Vaccination site reaction

Metabolic

Very common (10% or more): Hyperglycemia (up to 53%), hyponatremia (up to 49%), hypocalcemia (up to 47%), decreased appetite (up to 35%), hyperkalemia (up to 30%), hypomagnesemia (up to 29%), hypokalemia (up to 26%), hypercalcemia (up to 15%), hypoglycemia (up to 15.2%)

Common (1% to 10%): Diabetes mellitus, dehydration, hypoalbuminemia, hypermagnesemia, hypernatremia, hypophosphatemia

Uncommon (0.1% to 1%): Diabetic ketoacidosis, metabolic acidosis, tumor lysis syndrome

Rare (0.01% to 0.1%): Alkalosis, type 1 diabetes mellitus (including diabetic ketoacidosis)

Musculoskeletal

Very common (10% or more): Musculoskeletal pain (includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, pain in extremity, spinal pain, flank pain, muscle spasms, musculoskeletal disorder, osteitis, musculoskeletal stiffness, noncardiac chest pain, arthralgia, arthritis, arthropathy, joint effusion, psoriatic arthropathy, synovitis, involuntary muscle contractions, muscle twitching, polymyalgia rheumatica; up to 41%), arthralgia (up to 23%)

Common (1% to 10%): Increased blood creatine phosphokinase, myalgia, muscle spasms, arthritis, muscular weakness

Uncommon (0.1% to 1%): Myopathy, Sjogren's syndrome, spondyloarthropathy, myositis (including polymyositis), necrotizing myositis, rhabdomyolysis, polymyalgia rheumatica

Rare (0.01% to 0.1%): Polymyositis

Nervous system

Very common (10% or more): Headache (up to 33%), dizziness (includes dizziness, vertigo, positional vertigo; up to 20%)

Common (1% to 10%): Autoimmune neuropathy (including facial nerve paresis, abducens nerve paresis), lethargy, tremor, brain edema, cranial neuropathy, peripheral neuropathy, aphasia, immune-related neurological adverse reactions, peripheral sensory neuropathy

Uncommon (0.1% to 1%): Guillain-Barre syndrome, polyneuropathy, neuritis, peroneal nerve palsy, encephalitis, ataxia, dysarthria, aseptic meningitis, myasthenia gravis, autoimmune central neuropathy (encephalitis), syncope, myoclonus

Rare (0.01% to 0.1%): Meningism, neurosensory hypoacusis, myelitis

Frequency not reported: Meningitis, demyelination, myasthenic syndrome/myasthenia gravis, nerve paresis, motor dysfunction, autoimmune encephalitis, myasthenia gravis-like syndrome

Ocular

Common (1% to 10%): Blurred vision, conjunctivitis, uveitis, eye pain, dry eye

Uncommon (0.1% to 1%): Episcleritis, vitreous hemorrhage, iritis, eye edema, blepharitis, reduced visual acuity, foreign body sensation in eyes

Rare (0.01% to 0.1%): Scleritis, ocular myositis

Frequency not reported: Vogt-Koyanagi-Harada-like syndrome, orbital myositis, retinal detachment

Postmarketing reports: Serous retinal detachment, Vogt-Koyanagi-Harada syndrome

Oncologic

Common (1% to 10%): Tumor pain, cancer pain

Uncommon (0.1% to 1%): Paraneoplastic syndrome

Frequency not reported: Histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis)

Other

Very common (10% or more): Fatigue (includes asthenia, fatigue, malaise; up to 62%), increased alkaline phosphatase (up to 41%), pyrexia (includes pyrexia, tumor-associated fever; up to 40%), decreased weight (up to 32%), malaise (up to 18%), edema (includes peripheral edema, peripheral swelling, eyelid edema, face edema, generalized edema, localized edema, edema, periorbital edema; up to 17%), influenza-like illness (up to 14%), infusion-related reactions (up to 12%)

Common (1% to 10%): Chills, chest pain, sepsis, asthenia, pain

Uncommon (0.1% to 1%): Septic shock, multi-organ failure, systemic inflammatory response syndrome

Frequency not reported: Infusion reaction

Psychiatric

Very common (10% or more): Insomnia (up to 18%)

Common (1% to 10%): Depression, anxiety, decreased libido, confusional state

Uncommon (0.1% to 1%): Mental status change

Renal

Very common (10% or more): Increased creatinine (up to 42.7%)

Common (1% to 10%): Immune-mediated nephritis with renal dysfunction, acute kidney injury, renal failure, glomerulonephritis

Uncommon (0.1% to 1%): Tubulointerstitial nephritis, autoimmune nephritis, renal tubular acidosis, nephritis

Frequency not reported: Acute renal failure

Respiratory

Very common (10% or more): Cough (includes cough, productive cough, upper-airway cough syndrome; up to 37%), dyspnea (includes dyspnea, exertional dyspnea, dyspnea at rest; up to 27%), upper respiratory tract infection (includes upper respiratory tract infection, nasopharyngitis, pharyngitis, rhinitis; up to 23%), pneumonia (includes lower respiratory tract infection, bacterial lower respiratory tract infection, lung infection, pneumonia, adenoviral pneumonia, aspiration pneumonia, bacterial pneumonia, Klebsiella pneumonia, influenzal pneumonia, viral pneumonia, atypical pneumonia, organizing pneumonia, Pneumocystis jirovecii pneumonia, pseudomonal pneumonia; up to 14%)

Common (1% to 10%): Immune-mediated pneumonitis, pneumonitis, aspiration pneumonia, pleural effusion, pulmonary embolism, respiratory failure, influenza, lower respiratory tract infection, oropharyngeal pain, wheezing, nasal disorder, sinus congestion, respiratory tract infection, bronchitis

Uncommon (0.1% to 1%): Lung infiltration, acute respiratory distress syndrome, pulmonary edema, allergic rhinitis

Frequency not reported: Massive hemoptysis (in the setting of thrombocytopenia), interstitial lung disease