Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Published: November 27, 2017 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Publish Date: November 27, 2017 Introduction Grades Grade 5 The NCI Common Terminology Criteria for Adverse Grade refers to the severity of the AE. The CTCAE Grade 5 (Death) is not appropriate for some AEs Events is a descriptive terminology which can be displays Grades 1 through 5 with unique clinical and therefore is not an option. utilized for Adverse Event (AE) reporting. A grading descriptions of severity for each AE based on this (severity) scale is provided for each AE term. general guideline: Definitions A brief Definition is provided to clarify the meaning Grade 1 Mild; asymptomatic or mild symptoms; SOC of each AE term. A single dash (-) indicates a clinical or diagnostic observations only; System Organ Class (SOC), the highest level of the Definition is not available. intervention not indicated. MedDRA1 hierarchy, is identified by anatomical or Grade 2 Moderate; minimal, local or noninvasive physiological system, etiology, or purpose (e.g., Navigational Notes intervention indicated; limiting age- SOC Investigations for laboratory test results). A Navigational Note is used to assist the reporter in appropriate instrumental ADL*. CTCAE terms are grouped by MedDRA Primary choosing a correct AE. It may list other AEs that Grade 3 Severe or medically significant but not SOCs. Within each SOC, AEs are listed and should be considered in addition to or in place of immediately life-threatening; accompanied by descriptions of severity (Grade). the AE in question. A single dash (-) indicates a hospitalization or prolongation of Navigational Note has not been defined for the AE hospitalization indicated; disabling; CTCAE Terms term. An Adverse Event (AE) is any unfavorable and limiting self care ADL**. unintended sign (including an abnormal laboratory Grade 4 Life-threatening consequences; urgent Activities of Daily Living (ADL) finding), symptom, or disease temporally intervention indicated. *Instrumental ADL refer to preparing meals, associated with the use of a medical treatment or Grade 5 Death related to AE. shopping for groceries or clothes, using the procedure that may or may not be considered A Semi-colon indicates ‘or’ within the description telephone, managing money, etc. related to the medical treatment or procedure. An of the grade. **Self care ADL refer to bathing, dressing and AE is a term that is a unique representation of a undressing, feeding self, using the toilet, taking A single dash (-) indicates a Grade is not available. specific event used for medical documentation and medications, and not bedridden. Not all Grades are appropriate for all AEs. scientific analyses. Each CTCAE v4.0 term is a Therefore, some AEs are listed with fewer than five MedDRA LLT (Lowest Level Term). options for Grade selection. 1 CTCAE v5.0 incorporates certain elements of the MedDRA terminology. For further details on MedDRA refer to the MedDRA MSSO Web site (https://www.meddra.org/). Table of Contents Blood and lymphatic system disorders ............................................................................................ 3 Cardiac disorders ............................................................................................................................. 5 Congenital, familial and genetic disorders .................................................................................... 11 Ear and labyrinth disorders ............................................................................................................ 12 Endocrine disorders ....................................................................................................................... 14 Eye disorders .................................................................................................................................. 17 Gastrointestinal disorders ............................................................................................................. 22 General disorders and administration site conditions .................................................................. 40 Hepatobiliary disorders ................................................................................................................. 44 Immune system disorders ............................................................................................................. 47 Infections and infestations ............................................................................................................ 49 Injury, poisoning and procedural complications ........................................................................... 64 Investigations ................................................................................................................................. 78 Metabolism and nutrition disorders .............................................................................................. 84 Musculoskeletal and connective tissue disorders ......................................................................... 88 Neoplasms benign, malignant and unspecified (incl cysts and polyps) ......................................... 96 Nervous system disorders ............................................................................................................. 97 Pregnancy, puerperium and perinatal conditions ....................................................................... 107 Psychiatric disorders .................................................................................................................... 108 Renal and urinary disorders ......................................................................................................... 112 Reproductive system and breast disorders ................................................................................. 116 Respiratory, thoracic and mediastinal disorders ......................................................................... 123 Skin and subcutaneous tissue disorders ...................................................................................... 134 Social circumstances .................................................................................................................... 141 Surgical and medical procedures ................................................................................................. 142 Vascular disorders ........................................................................................................................ 143 Blood and lymphatic system disorders CTCAE Term Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Anemia Hemoglobin (Hgb) <LLN - 10.0 Hgb <10.0 - 8.0 g/dL; <6.2 - Hgb <8.0 g/dL; <4.9 mmol/L; Life-threatening Death g/dL; <LLN - 6.2 mmol/L; <LLN 4.9 mmol/L; <100 - 80g/L <80 g/L; transfusion indicated consequences; urgent - 100 g/L intervention indicated Definition: A disorder characterized by a reduction in the amount of hemoglobin in 100 ml of blood. Signs and symptoms of anemia may include pallor of the skin and mucous membranes, shortness of breath, palpitations of the heart, soft systolic murmurs, lethargy, and fatigability. Navigational Note: - Bone marrow hypocellular Mildly hypocellular or <=25% Moderately hypocellular or Severely hypocellular or >50 - Aplastic persistent for longer Death reduction from normal >25 - <50% reduction from <=75% reduction cellularity than 2 weeks cellularity for age normal cellularity for age from normal for age Definition: A disorder characterized by the inability of the bone marrow to produce hematopoietic elements. Navigational Note: - Disseminated intravascular - Laboratory findings with no Laboratory findings and Life-threatening Death coagulation bleeding bleeding consequences; urgent intervention indicated Definition: A disorder characterized by systemic pathological activation of blood clotting mechanisms which results in clot formation throughout the body. There is an increase in the risk of hemorrhage as the body is depleted of platelets and coagulation factors. Navigational Note: - Eosinophilia >ULN and >Baseline - Steroids initiated - - Definition: A disorder characterized by laboratory test results that indicate an increased number of eosinophils in the blood. Navigational Note: - Febrile neutropenia - - ANC <1000/mm3 with a single Life-threatening Death temperature of >38.3 degrees consequences; urgent C (101 degrees F) or a intervention indicated sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour Definition: A disorder characterized by an ANC <1000/mm3 and a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour. Navigational Note: - Hemolysis Laboratory evidence of Evidence of hemolysis and Transfusion or medical Life-threatening Death hemolysis only (e.g., direct >=2 g decrease in hemoglobin intervention indicated (e.g., consequences; urgent antiglobulin test; DAT; steroids) intervention indicated Coombs'; schistocytes; decreased haptoglobin) Definition: A disorder characterized by laboratory test results that indicate widespread erythrocyte cell membrane destruction. Navigational Note: - CTCAE v5.0 – November 27, 2017 Page 3 Blood and lymphatic system disorders CTCAE Term Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Hemolytic uremic syndrome - - Laboratory findings with Life-threatening