NCIC药物副反应分级
COMMON TOXICITY CRITERIA (CTC)
Grade
Adverse Event01234
ALLERGY/IMMUNOLOGY
Allergic reaction/ hypersensitivity (including drug fever)none transient rash, drug
fever <38°C (<100.4°F)
urticaria, drug fever
≥38°C (≥100.4°F),
and/or asymptomatic
bronchospasm
symptomatic
bronchospasm,
requiring parenteral
medication(s), with or
without urticaria;
allergy-related
edema/angioedema
anaphylaxis
Note: Isolated urticaria, in the absence of other manifestations of an allergic or hypersensitivity reaction, is graded in the DERMATOLOGY/SKIN category.
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)none mild, not requiring
treatment
moderate, requiring
treatment
--
Autoimmune reaction none serologic or other
evidence of
autoimmune reaction
but patient is
asymptomatic (e.g.,
vitiligo), all organ
function is normal and
no treatment is required evidence of
autoimmune reaction
involving a non-
essential organ or
function (e.g.,
hypothyroidism),
requiring treatment
other than
immunosuppressive
drugs
reversible autoimmune
reaction involving
function of a major
organ or other adverse
event (e.g., transient
colitis or anemia),
requiring short-term
immunosuppressive
treatment
autoimmune reaction
causing major grade 4
organ dysfunction;
progressive and
irreversible reaction;
long-term
administration of high-
dose immuno-
suppressive therapy
required
Also consider Hypothyroidism, Colitis, Hemoglobin, Hemolysis.
Serum sickness none--present-Urticaria is graded in the DERMATOLOGY/SKIN category if it occurs as an isolated symptom. If it occurs with other manifestations of allergic or hypersensitivity reaction, grade as Allergic reaction/hypersensitivity above.
Vasculitis none mild, not requiring
treatment symptomatic, requiring
medication
requiring steroids ischemic changes or
requiring amputation
Allergy/Immunology - Other (Specify, __________)none mild moderate severe life-threatening or
disabling
AUDITORY/HEARING
Conductive hearing loss is graded as Middle ear/hearing in the AUDITORY/HEARING category. Earache is graded in the PAIN category.
External auditory canal normal external otitis with
erythema or dry
desquamation external otitis with
moist desquamation
external otitis with
discharge, mastoiditis
necrosis of the canal
soft tissue or bone
Note: Changes associated with radiation to external ear (pinnae) are graded under Radiation dermatitis in the DERMATOLOGY/SKIN category.
Adverse Event01234
Inner ear/hearing normal hearing loss on
audiometry only tinnitus or hearing loss,
not requiring hearing
aid or treatment
tinnitus or hearing loss,
correctable with hearing
aid or treatment
severe unilateral or
bilateral hearing loss
(deafness), not
correctable
Middle ear/hearing normal serous otitis without
subjective decrease in
hearing serous otitis or infection
requiring medical
intervention; subjective
decrease in hearing;
rupture of tympanic
membrane with
discharge
otitis with discharge,
mastoiditis or
conductive hearing loss
necrosis of the canal
soft tissue or bone
Auditory/Hearing - Other (Specify, __________)normal mild moderate severe life-threatening or
disabling
BLOOD/BONE MARROW
Bone marrow cellularity normal for age mildly hypocellular or
≤25% reduction from
normal cellularity for
age moderately hypocellular
or >25 - ≤50%
reduction from normal
cellularity for age or >2
but <4 weeks to
recovery of normal
bone marrow cellularity
severely hypocellular or
>50 - ≤75% reduction
in cellularity for age or
4 - 6 weeks to recovery
of normal bone marrow
cellularity
aplasia or >6 weeks to
recovery of normal
bone marrow cellularity
Normal ranges:
children (≤18 years)90% cellularity
average
younger adults (19-59)60 - 70%
cellularity average
older adults (≥60 years)50% cellularity
average
Note: Grade Bone marrow cellularity only for changes related to treatment not disease.
CD4 count WNL Hemoglobin (Hgb)WNL 80 - <100 g/L 4.9 - <6.2 mmol/L 6.5 - <8.0 g/dL 65 - <80 g/L 4.0 - <4.9 mmol/L <6.5 g/dL <65 g/L <4.0 mmol/L For leukemia studies or bone marrow infiltrative/ myelophthisic processes, if specified in the protocol.WNL10 - <25% decrease from pretreatment 25 - <50% decrease from pretreatment 50 - <75% decrease from pretreatment ≥75% decrease from pretreatment Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis, other)none only laboratory evidence of hemolysis [e.g., direct antiglobulin test (DAT, Coombs’) schistocytes] evidence of red cell destruction and ≥2gm decrease in hemoglobin, no transfusion requiring transfusion and/or medical intervention (e.g., steroids) catastrophic consequences of hemolysis (e.g., renal failure, hypotension, bronchospasm, emergency splenectomy) Also consider Haptoglobin, Hemoglobin. Adverse Event01234 Leukocytes (total WBC)WNL ≥2000 - <3000/mm3 ≥1.0 - <2.0 x 109 /L ≥1000 - <2000/mm3 <1.0 x 109 /L <1000/mm3 For BMT studies, if specified in the protocol.WNL≥2.0 - <3.0 X 109/L ≥2000 - <3000/mm3 ≥1.0 - <2.0 x 109 /L ≥1000 - <2000/mm3 ≥0.5 - <1.0 x 109 /L ≥500 - <1000/mm3 <0.5 x 109 /L <500/mm3 For pediatric BMT studies (using age, race and sex normal values), if specified in the protocol. ≥75 - <100% LLN≥50 - <75% LLN≥25 - 50% LLN<25% LLN Lymphopenia WNL ≥500 - <1000/mm3 <0.5 x 109 /L <500/mm3 - For pediatric BMT studies (using age, race and sex normal values), if specified in the protocol. ≥75 - <100%LLN≥50 - <75%LLN≥25 - <50%LLN<25%LLN Neutrophils/granulocytes (ANC/AGC)WNL≥1.5 - <2.0 x 109 /L ≥1500 - <2000/mm3 ≥1.0 - <1.5 x 109 /L ≥1000 - <1500/mm3 ≥0.5 - <1.0 x 109 /L ≥500 - <1000/mm3 <0.5 x 109 /L <500/mm3 For BMT studies, if specified in the protocol.WNL≥1.0 - <1.5 x 109 /L ≥1000 - <1500/mm3 ≥0.5 - <1.0 x 109 /L ≥500 - <1000/mm3 ≥0.1 - <0.5 x 109 /L ≥100 - <500/mm3 <0.1 x 109 /L <100/mm3 For leukemia studies or bone marrow infiltrative/ myelophthisic process, if specified in the protocol.WNL10 - <25% decrease from baseline 25 - <50% decrease from baseline 50 - <75% decrease from baseline ≥75% decrease from baseline Platelets WNL ≥50,000 - <75,000/mm3 ≥10.0 - <50.0 x 109 /L ≥10,000 - <50,000/mm3 <10.0 x 109 /L <10,000/mm3 For BMT studies, if specified in the protocol.WNL≥50.0 - <75.0 x 109 /L ≥50,000 - <75,000/mm3 ≥20.0 - <50.0 x 109 /L ≥20,000 - <50,000/mm3 ≥10.0 - <20.0 x 109 /L ≥10,000 - <20,000/mm3 <10.0 x 109 /L <10,000/mm3 For leukemia studies or bone marrow infiltrative/ myelophthisic process, if specified in the protocol.WNL10 - <25% decrease from baseline 25 - <50% decrease from baseline 50 - <75% decrease from baseline ≥75% decrease from baseline Transfusion: Platelets none--yes platelet transfusions and other measures required to improve platelet increment; platelet transfusion refractoriness associated with life-threatening bleeding. (e.g., HLA or cross matched platelet transfusions) For BMT studies, if specified in the protocol.none 1 platelet transfusion in 24 hours 2 platelet transfusions in 24 hours ≥3 platelet transfusions in 24 hours platelet transfusions and other measures required to improve platelet increment; platelet transfusion refractoriness associated with life-threatening bleeding. (e.g., HLA or cross matched platelet transfusions) Also consider Platelets. Adverse Event01234 Transfusion: pRBCs none--yes- For BMT studies, if specified in the protocol.none≤2 u pRBC in 24 hours elective or planned 3 u pRBC in 2 4 hours elective or planned ≥4 u pRBC in 24 hours hemorrhage or hemolysis associated with life-threatening anemia; medical intervention required to improve hemoglobin For pediatric BMT studies, if specified in the protocol.none≤15mL/kg in 24 hours elective or planned >15 - ≤30mL/kg in 24 hours elective or planned >30mL/kg in 24 hours hemorrhage or hemolysis associated with life-threatening anemia; medical intervention required to improve hemoglobin Also consider Hemoglobin. Blood/Bone Marrow - Other (Specify, __________)none mild moderate severe life-threatening or disabling CARDIOVASCULAR (ARRHYTHMIA) Conduction abnormality/ Atrioventricular heart block none asymptomatic, not requiring treatment (e.g., Mobitz type I second-degree AV block, Wenckebach) symptomatic, but not requiring treatment symptomatic and requiring treatment (e.g., Mobitz type II second-degree AV block, third-degree AV block) life-threatening (e.g., arrhythmia associated with CHF, hypotension, syncope, shock) Nodal/junctional arrhythmia/dysrhythmia none asymptomatic, not requiring treatment symptomatic, but not requiring treatment symptomatic and requiring treatment life-threatening (e.g., arrhythmia associated with CHF, hypotension, syncope, shock) Palpitations none present---Note: Grade palpitations only in the absence of a documented arrhythmia. Prolonged QTc interval (QTc >0.48 seconds)none asymptomatic, not requiring treatment symptomatic, but not requiring treatment symptomatic and requiring treatment life-threatening (e.g., arrhythmia associated with CHF, hypotension, syncope, shock) Sinus bradycardia none asymptomatic, not requiring treatment symptomatic, but not requiring treatment symptomatic and requiring treatment life-threatening (e.g., arrhythmia associated with CHF, hypotension, syncope, shock) Sinus tachycardia none asymptomatic, not requiring treatment symptomatic, but not requiring treatment symptomatic and requiring treatment of underlying cause - Supraventricular arrhythmias (SVT/atrial fibrillation/ flutter)none asymptomatic, not requiring treatment symptomatic, but not requiring treatment symptomatic and requiring treatment life-threatening (e.g., arrhythmia associated with CHF, hypotension, syncope, shock) Syncope (fainting) is graded in the NEUROLOGY category. Vasovagal episode none-present without loss of consciousness present with loss of consciousness - Adverse Event01234 Ventricular arrhythmia (PVCs/bigeminy/trigeminy/ ventricular tachycardia)none asymptomatic, not requiring treatment symptomatic, but not requiring treatment symptomatic and requiring treatment life-threatening (e.g., arrhythmia associated with CHF, hypotension, syncope, shock) Cardiovascular/ Arrhythmia - Other (Specify, ___________)none asymptomatic, not requiring treatment symptomatic, but not requiring treatment symptomatic, and requiring treatment of underlying cause life-threatening (e.g., arrhythmia associated with CHF, hypotension, syncope, shock) CARDIOVASCULAR (GENERAL) Acute vascular leak syndrome absent-symptomatic, but not requiring fluid support respiratory compromise or requiring fluids life-threatening; requiring pressor support and/or ventilatory support Cardiac-ischemia/infarction none non-specific T - wave flattening or changes asymptomatic, ST - and T - wave changes suggesting ischemia angina without evidence of infarction acute myocardial infarction Cardiac left ventricular function normal asymptomatic decline of resting ejection fraction of ≥10% but <20% of baseline value; shortening fraction ≥24% but <30% asymptomatic but resting ejection fraction below LLN for laboratory or decline of resting ejection fraction ≥20% of baseline value; <24% shortening fraction CHF responsive to treatment severe or refractory CHF or requiring intubation CNS cerebrovascular ischemia is graded in the NEUROLOGY category. Cardiac troponin I (cTnI)normal--levels consistent with unstable angina as defined by the manufacturer levels consistent with myocardial infarction as defined by the manufacturer Cardiac troponin T (cTnT)normal≥0.03 - <0.05 ng/mL≥0.05 - <0.1 ng/mL≥0.1 - <0.2 ng/mL≥0.2 ng/mL Edema none asymptomatic, not requiring therapy symptomatic, requiring therapy symptomatic edema limiting function and unresponsive to therapy or requiring drug discontinuation anasarca (severe generalized edema) Hypertension none asymptomatic, transient increase by >20 mmHg (diastolic) or to >150/100* if previously WNL; not requiring treatment recurrent or persistent or symptomatic increase by >20 mmHg (diastolic) or to >150/100* if previously WNL; not requiring treatment requiring therapy or more intensive therapy than previously hypertensive crisis *Note: For pediatric patients, use age and sex appropriate normal values >95th percentile ULN. Adverse Event01234 Hypotension none changes, but not requiring therapy (including transient orthostatic hypotension)requiring brief fluid replacement or other therapy but not hospitalization; no physiologic consequences requiring therapy and sustained medical attention, but resolves without persisting physiologic consequences shock (associated with acidemia and impairing vital organ function due to tissue hypoperfusion) Also consider Syncope (fainting). Notes:Angina or MI is graded as Cardiac-ischemia/infarction in the CARDIOVASCULAR (GENERAL) category. For pediatric patients, systolic BP 65 mmHg or less in infants up to 1 year old and 70 mmHg or less in children older than 1 year of age, use two successive or three measurements in 24 hours. Myocarditis none--CHF responsive to treatment severe or refractory CHF Operative injury of vein/artery none primary suture repair for injury, but not requiring transfusion primary suture repair for injury, requiring transfusion vascular occlusion requiring surgery or bypass for injury myocardial infarction; resection of organ (e.g., bowel, limb) Pericardial effusion/ pericarditis none asymptomatic effusion, not requiring treatment pericarditis (rub, ECG changes, and/or chest pain) with physiologic consequences tamponade (drainage or pericardial window required) Peripheral arterial ischemia none-brief episode of ischemia managed non- surgically and without permanent deficit requiring surgical intervention life-threatening or with permanent functional deficit (e.g., amputation) Phlebitis (superficial)none-present--Notes:Injection site reaction is graded in the DERMATOLOGY/SKIN category. Thrombosis/embolism is graded in the CARDIOVASCULAR (GENERAL) category. Syncope (fainting) is graded in the NEUROLOGY category. Thrombosis/embolism none-deep vein thrombosis, not requiring anticoagulant deep vein thrombosis, requiring anticoagulant therapy embolic event including pulmonary embolism Vein/artery operative injury is graded as Operative injury of vein/artery in the CARDIOVASCULAR (GENERAL) category. Visceral arterial ischemia (non-myocardial)none-brief episode of ischemia managed non- surgically and without permanent deficit requiring surgical intervention life-threatening or with permanent functional deficit (e.g., resection of ileum) Cardiovascular/ General - Other (Specify, ______________)none mild moderate severe life-threatening or disabling Adverse Event01234 COAGULATION Note: See the HEMORRHAGE category for grading the severity of bleeding events. DIC (disseminated intravascular coagulation)absent--laboratory findings present with no bleeding laboratory findings and bleeding Also consider Platelets. Note: Must have increased fibrin split products or D-dimer in order to grade as DIC. Fibrinogen WNL≥0.75 - <1.0 x LLN≥0.5 - <0.75 x LLN≥0.25 - <0.5 x LLN<0.25 x LLN For leukemia studies or bone marrow infiltrative/ myelophthisic process, if specified in the protocol.WNL<20% decrease from pretreatment value or LLN ≥20 - <40% decrease from pretreatment value or LLN ≥40 - <70% decrease from pretreatment value or LLN <50 mg Partial thromboplastin time (PTT) WNL>ULN - ≤1.5 x ULN>1.5 - ≤2 x ULN>2 x ULN-Phlebitis is graded in the CARDIOVASCULAR (GENERAL) category. Prothrombin time (PT)WNL>ULN - ≤1.5 x ULN>1.5 - ≤2 x ULN>2 x ULN-Thrombosis/embolism is graded in the CARDIOVASCULAR (GENERAL) category. Thrombotic microangiopathy (e.g., thrombotic thrombocytopenic purpura/TTP or hemolytic uremic syndrome/HUS)absent--laboratory findings present without clinical consequences laboratory findings and clinical consequences, (e.g., CNS hemorrhage/ bleeding or thrombosis/ embolism or renal failure) requiring therapeutic intervention For BMT studies, if specified in the protocol.-evidence of RBC destruction (schistocytosis) without clinical consequences evidence of RBC destruction with elevated creatinine (≤3 x ULN) evidence of RBC destruction with creatinine (>3 x ULN) not requiring dialysis evidence of RBC destruction with renal failure requiring dialysis and/or encephalopathy Also consider Hemoglobin, Platelets, Creatinine. Note: Must have microangiopathic changes on blood smear (e.g., schistocytes, helmet cells, red cell fragments). Coagulation - Other (Specify, __________)none mild moderate severe life-threatening or disabling CONSTITUTIONAL SYMPTOMS Fatigue (lethargy, malaise, asthenia)none increased fatigue over baseline, but not altering normal activities moderate (e.g., decrease in performance status by 1 ECOG level or 20% Karnofsky or Lansky) or causing difficulty performing some activities severe (e.g., decrease in performance status by ≥2 ECOG levels or 40% Karnofsky or Lansky) or loss of ability to perform some activities bedridden or disabling Note: See Appendix III for performance status scales. Adverse Event01234 Fever (in the absence of neutropenia, where neutropenia is defined as AGC <1.0 x 109/L)none38.0 - 39.0°C (100.4 - 102.2°F) 39.1 - 40.0°C (102.3 - 104.0°F ) >40.0°C (>104.0°F ) for <24hrs >40.0°C (>104.0°F ) for >24hrs Also consider Allergic reaction/hypersensitivity. Note: The temperature measurements listed above are oral or tympanic. Hot flashes/flushes are graded in the ENDOCRINE category. Rigors, chills none mild, requiring symptomatic treatment (e.g., blanket) or non- narcotic medication severe and/or prolonged, requiring narcotic medication not responsive to narcotic medication - Sweating (diaphoresis) normal mild and occasional frequent or drenching--Weight gain<5% 5 - <10%10 - <20%≥20%-Also consider Ascites, Edema, Pleural effusion (non-malignant). Weight gain associated with Veno-Occlusive Disease (VOD) for BMT studies, if specified in the protocol.<2%≥2 - <5%≥5 - <10%≥10% or as ascites≥10% or fluid retention resulting in pulmonary failure Also consider Ascites, Edema, Pleural effusion (non-malignant). Weight loss<5% 5 - <10%10 - <20%≥20%-Also consider Vomiting, Dehydration, Diarrhea. Constitutional Symptoms -Other (Specify, __________)none mild moderate severe life-threatening or disabling DERMATOLOGY/SKIN Alopecia normal mild hair loss pronounced hair loss-- Bruising (in absence of grade 3 or 4 thrombocytopenia)none localized or in dependent area generalized-- Note:Bruising resulting from grade 3 or 4 thrombocytopenia is graded as Petechiae/purpura and Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia in the HEMORRHAGE category, not in the DERMATOLOGY/SKIN category. Dry skin normal controlled with emollients not controlled with emollients -- Erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)absent-scattered, but not generalized eruption severe or requiring IV fluids (e.g., generalized rash or painful stomatitis) life-threatening (e.g., exfoliative or ulcerating dermatitis or requiring enteral or parenteral nutritional support) Flushing absent present--- Hand-foot skin reaction none skin changes or dermatitis without pain (e.g., erythema, peeling)skin changes with pain, not interfering with function skin changes with pain, interfering with function - Injection site reaction none pain or itching or erythema pain or swelling, with inflammation or phlebitis ulceration or necrosis that is severe or prolonged, or requiring surgery - Adverse Event01234 Nail changes normal discoloration or ridging (koilonychia) or pitting partial or complete loss of nail(s) or pain in nailbeds -- Petechiae is graded in the HEMORRHAGE category. Photosensitivity none painless erythema painful erythema erythema with desquamation - Pigmentation changes (e.g., vitiligo)none localized pigmentation changes generalized pigmentation changes -- Pruritus none mild or localized, relieved spontaneously or by local measures intense or widespread, relieved spontaneously or by systemic measures intense or widespread and poorly controlled despite treatment - Purpura is graded in the HEMORRHAGE category. Radiation dermatitis none faint erythema or dry desquamation moderate to brisk erythema or a patchy moist desquamation, mostly confined to skin folds and creases; moderate edema confluent moist desquamation ≥1.5 cm diameter and not confined to skin folds; pitting edema skin necrosis or ulceration of full thickness dermis; may include bleeding not induced by minor trauma or abrasion Note: Pain associated with radiation dermatitis is graded separately in the PAIN category as Pain due to radiation. Radiation recall reaction (reaction following chemotherapy in the absence of additional radiation therapy that occurs in a previous radiation port)none faint erythema or dry desquamation moderate to brisk erythema or a patchy moist desquamation, mostly confined to skin folds and creases; moderate edema confluent moist desquamation ≥1.5 cm diameter and not confined to skin folds; pitting edema skin necrosis or ulceration of full thickness dermis; may include bleeding not induced by minor trauma or abrasion Rash/desquamation none macular or papular eruption or erythema without associated symptoms macular or papular eruption or erythema with pruritus or other associated symptoms covering <50% of body surface or localized desquamation or other lesions covering <50% of body surface area symptomatic generalized erythroderma or macular, papular or vesicular eruption or desquamation covering ≥50% of body surface area generalized exfoliative dermatitis or ulcerative dermatitis Also consider Allergic reaction/hypersensitivity. Note: Stevens-Johnson syndrome is graded separately as Erythema multiforme in the DERMATOLOGY/SKIN category. Rash/dermatitis associated with high-dose chemotherapy or BMT studies.none faint erythema or dry desquamation moderate to brisk erythema or a patchy moist desquamation, mostly confined to skin folds and creases; moderate edema confluent moist desquamation ≥1.5 cm diameter and not confined to skin folds; pitting edema skin necrosis or ulcera- tion of full thickness dermis; may include spontaneous bleeding not induced by minor trauma or abrasion Rash/desquamation associated with graft versus host disease (GVHD) for BMT studies, if specified in the protocol.None macular or papular eruption or erythema covering <25% of body surface area without associated symptoms macular or papular eruption or erythema with pruritus or other associated symptoms covering ≥25 - <50% of body surface or localized desquamation or other lesions covering ≥25 - <50% of body surface area symptomatic generalized erythroderma or symptomatic macular, papular or vesicular eruption, with bullous formation, or desquamation covering ≥50% of body surface area generalized exfoliative dermatitis or ulcerative dermatitis or bullous formation Also consider Allergic reaction/hypersensitivity. Note: Stevens-Johnson syndrome is graded separately as Erythema multiforme in the DERMATOLOGY/SKIN category. Adverse Event01234 Urticaria (hives, welts, wheals)none requiring no medication requiring PO or topical treatment or IV medication or steroids for <24 hours requiring IV medication or steroids for ≥24 hours - Wound-infectious none cellulitis superficial infection infection requiring IV antibiotics necrotizing fasciitis Wound-non-infectious none incisional separation incisional hernia fascial disruption without evisceration fascial disruption with evisceration Dermatology/Skin - Other (Specify, ________)none mild moderate severe life-threatening or disabling ENDOCRINE Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae) absent-present-- Also consider Hyperglycemia, Hypokalemia. Feminization of male absent--present-Gynecomastia none mild pronounced or painful pronounced or painful and requiring surgery - Hot flashes/flushes none mild or no more than 1 per day moderate and greater than 1 per day -- Hypothyroidism absent asymptomatic,TSH elevated, no therapy given symptomatic or thyroid replacement treatment given patient hospitalized for manifestations of hypothyroidism myxedema coma Masculinization of female absent--present-SIADH (syndrome of inappropriate antidiuretic hormone) absent--present- Endocrine - Other (Specify, __________)none mild moderate severe life-threatening or disabling GASTROINTESTINAL Amylase is graded in the METABOLIC/LABORATORY category. Anorexia none loss of appetite oral intake significantly decreased requiring IV fluids requiring feeding tube or parenteral nutrition Ascites (non-malignant)none asymptomatic symptomatic, requiring diuretics symptomatic, requiring therapeutic paracentesis life-threatening physiologic consequences Colitis none-abdominal pain with mucus and/or blood in stool abdominal pain, fever, change in bowel habits with ileus or peritoneal signs, and radiographic or biopsy documentation perforation or requiring surgery or toxic megacolon Also consider Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia, Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia, Melena/GI bleeding, Rectal bleeding/hematochezia, Hypotension. Constipation none requiring stool softener or dietary modification requiring laxatives obstipation requiring manual evacuation or enema obstruction or toxic megacolon Adverse Event01234 Dehydration none dry mucous membranes and/or diminished skin turgor requiring IV fluid replacement (brief) requiring IV fluid replacement (sustained) physiologic consequences requiring intensive care; hemodynamic collapse Also consider Diarrhea, Vomiting, Stomatitis/pharyngitis (oral/pharyngeal mucositis), Hypotension. Diarrhea patients without colostomy:none increase of <4 stools/day over pre- treatment increase of 4-6 stools/day, or nocturnal stools increase of ≥7 stools/day or incontinence; or need for parenteral support for dehydration physiologic consequences requiring intensive care; or hemodynamic collapse patients with a colostomy:none mild increase in loose, watery colostomy output compared with pretreatment moderate increase in loose, watery colostomy output compared with pretreatment, but not interfering with normal activity severe increase in loose, watery colostomy output compared with pretreatment, interfering with normal activity physiologic consequences, requiring intensive care; or hemodynamic collapse Diarrhea associated with graft versus host disease (GVHD) for BMT studies, if specified in the protocol.None>500 - ≤1000mL of diarrhea/day >1000 - ≤1500mL of diarrhea/day >1500mL of diarrhea/day severe abdominal pain with or without ileus For pediatric BMT studies, if specified in the protocol.>5 - ≤10 mL/kg of diarrhea/day >10 - ≤15 mL/kg of diarrhea/day >15 mL/kg of diarrhea/day - Also consider Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia, Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia, Pain, Dehydration, Hypotension. Duodenal ulcer (requires radiographic or endoscopic documentation)none-requiring medical management or non- surgical treatment uncontrolled by outpatient medical management; requiring hospitalization perforation or bleeding, requiring emergency surgery Dyspepsia/heartburn none mild moderate severe- Dysphagia, esophagitis, odynophagia (painful swallowing)none mild dysphagia, but can eat regular diet dysphagia, requiring predominantly pureed, soft, or liquid diet dysphagia, requiring IV hydration complete obstruction (cannot swallow saliva) requiring enteral or parenteral nutritional support, or perforation Note: If the adverse event is radiation-related, grade either under Dysphagia-esophageal related to radiation or Dysphagia-pharyngeal related to radiation. Dysphagia-esophageal related to radiation none mild dysphagia, but can eat regular diet dysphagia, requiring predominantly pureed, soft, or liquid diet Dysphagia, requiring feeding tube, IV hydration or hyperalimentation complete obstruction (cannot swallow saliva); ulceration with bleeding not induced by minor trauma or abrasion or perforation Also consider Pain due to radiation, Mucositis due to radiation. Note: Fistula is graded separately as Fistula-esophageal. Dysphagia-pharyngeal related to radiation none mild dysphagia, but can eat regular diet dysphagia, requiring predominantly pureed, soft, or liquid diet dysphagia, requiring feeding tube, IV hydration or hyperalimentation complete obstruction (cannot swallow saliva); ulceration with bleeding not induced by minor trauma or abrasion or perforation Also consider Pain due to radiation, Mucositis due to radiation. Note: Fistula is graded separately as Fistula-pharyngeal. Fistula-esophageal none--present requiring surgery Fistula-intestinal none--present requiring surgery Adverse Event01234 Fistula-pharyngeal none--present requiring surgery Fistula-rectal/anal none--present requiring surgery Flatulence none mild moderate-- Gastric ulcer (requires radiographic or endoscopic documentation)none-requiring medical management or non- surgical treatment bleeding without perforation, uncon- trolled by outpatient medical management; requiring hospitalization or surgery perforation or bleeding, requiring emergency surgery Also consider Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia, Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia. Gastritis none-requiring medical management or non- surgical treatment uncontrolled by out- patient medical management; requiring hospitalization or surgery life-threatening bleeding, requiring emergency surgery Also consider Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia, Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia. Hematemesis is graded in the HEMORRHAGE category. Hematochezia is graded in the HEMORRHAGE category as Rectal bleeding/hematochezia. Ileus (or neuroconstipation)none-intermittent, not requiring intervention requiring non-surgical intervention requiring surgery Mouth dryness normal mild moderate-- Mucositis Notes:Mucositis not due to radiation is graded in the GASTROINTESTINAL category for specific sites: Colitis, Esophagitis, Gastritis, Stomatitis/pharyngitis (oral/pharyngeal mucositis), and Typhlitis; or the RENAL/GENITOURINARY category for Vaginitis. Radiation-related mucositis is graded as Mucositis due to radiation. Mucositis due to radiation none erythema of the mucosa patchy pseudomembra- nous reaction (patches generally ≤1.5 cm in diameter and non- contiguous)confluent pseudomem- branous reaction (contiguous patches generally >1.5 cm in diameter) necrosis or deep ulceration; may include bleeding not induced by minor trauma or abrasion Also consider Pain due to radiation. Notes:Grade radiation mucositis of the larynx here. Dysphagia related to radiation is also graded as either Dysphagia-esophageal related to radiation or Dysphagia-pharyngeal related to radiation, depending on the site of treatment. Nausea none able to eat oral intake significantly decreased no significant intake, requiring IV fluids - Pancreatitis none--abdominal pain with pancreatic enzyme elevation complicated by shock (acute circulatory failure) Also consider Hypotension. Note: Amylase is graded in the METABOLIC/LABORATORY category. Pharyngitis is graded in the GASTROINTESTINAL category as Stomatitis/pharyngitis (oral/pharyngeal mucositis). Grade Adverse Event01234 Proctitis none increased stool frequency, occasional blood-streaked stools or rectal discomfort (including hemorrhoids) not requiring medication increased stool frequency, bleeding, mucus discharge, or rectal discomfort requiring medication; anal fissure increased stool fre- quency/diarrhea requir- ing parenteral support; rectal bleeding requir- ing transfusion; or per- sistent mucus discharge, necessitating pads perforation, bleeding or necrosis or other life- threatening complication requiring surgical intervention (e.g., colostomy) Also consider Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia, Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia, Pain due to radiation. Notes:Fistula is graded separately as Fistula-rectal/anal. Proctitis occurring more than 90 days after the start of radiation therapy is graded in the RTOG/EORTC Late Radiation Morbidity Scoring Scheme. (See Appendix IV) Salivary gland changes none slightly thickened saliva; may have slightly altered taste (e.g., metallic); additional fluids may be required thick, ropy, sticky saliva; markedly altered taste; alteration in diet required -acute salivary gland necrosis Sense of smell normal slightly altered markedly altered-- Stomatitis/pharyngitis (oral/pharyngeal mucositis)none painless ulcers, erythema, or mild soreness in the absence of lesions painful erythema, edema, or ulcers, but can eat or swallow painful erythema, edema, or ulcers requiring IV hydration severe ulceration or requires parenteral or enteral nutritional support or prophylactic intubation For BMT studies, if specified in the protocol.none painless ulcers, erythema, or mild soreness in the absence of lesions painful erythema, edema or ulcers but can swallow painful erythema, edema, or ulcers preventing swallowing or requiring hydration or parenteral (or enteral) nutritional support severe ulceration requiring prophylactic intubation or resulting in documented aspiration pneumonia Note: Radiation-related mucositis is graded as Mucositis due to radiation. Taste disturbance (dysgeusia) normal slightly altered markedly altered-- Typhlitis (inflammation of the cecum)none--abdominal pain, diarrhea, fever, and radiographic or biopsy documentation perforation, bleeding or necrosis or other life- threatening complication requiring surgical intervention (e.g., colostomy) Also consider Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia, Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia, Hypotension, Febrile neutropenia. Vomiting none 1 episode in 24 hours over pretreatment 2-5 episodes in 24 hours over pretreatment ≥6 episodes in 24 hours over pretreatment; or need for IV fluids requiring parenteral nutrition; or physiologic consequences requiring intensive care; hemodynamic collapse Also consider Dehydration. Weight gain is graded in the CONSTITUTIONAL SYMPTOMS category. Weight loss is graded in the CONSTITUTIONAL SYMPTOMS category. Gastrointestinal - Other (Specify, __________)none mild moderate severe life-threatening or disabling Grade Adverse Event01234 HEMORRHAGE Notes:Transfusion in this section refers to pRBC infusion. For any bleeding with grade 3 or 4 platelets (<50,000), always grade Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia. Also consider Platelets, Transfusion: pRBCs, and Transfusion: platelets in addition to grading severity by grading the site or type of bleeding. If the site or type of Hemorrhage/bleeding is listed, also use the grading that incorporates the site of bleeding: CNS Hemorrhage/bleeding, Hematuria, Hematemesis, Hemoptysis, Hemorrhage/bleeding with surgery, Melena/lower GI bleeding, Petechiae/purpura (Hemorrhage/bleeding into skin), Rectal bleeding/hematochezia, Vaginal bleeding. If the platelet count is ≥50,000 and the site or type of bleeding is listed, grade the specific site. If the site or type is not listed and the platelet count is ≥50,000, grade Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia and specify the site or type in the OTHER category. Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia none mild without transfusion requiring transfusion catastrophic bleeding, requiring major non- elective intervention Also consider Platelets, Hemoglobin, Transfusion: platelets, Transfusion: pRBCs, site or type of bleeding. If the site is not listed, grade as Hemorrhage-Other (Specify site, ___________). Note:This adverse event must be graded for any bleeding with grade 3 or 4 thrombocytopenia. Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia none mild without transfusion requiring transfusion catastrophic bleeding requiring major non- elective intervention Also consider Platelets, Hemoglobin, Transfusion: platelets, Transfusion: pRBCs, Hemorrhage - Other (Specify site, ___________). Note:Bleeding in the absence of grade 3 or 4 thrombocytopenia is graded here only if the specific site or type of bleeding is not listed elsewhere in the HEMORRHAGE category. Also grade as Other in the HEMORRHAGE category. CNS hemorrhage/bleeding none--bleeding noted on CT or other scan with no clinical consequences hemorrhagic stroke or hemorrhagic vascular event (CVA) with neurologic signs and symptoms Epistaxis none mild without transfusion -requiring transfusion catastrophic bleeding, requiring major non- elective intervention Hematemesis none mild without transfusion -requiring transfusion catastrophic bleeding, requiring major non- elective intervention Hematuria (in the absence of vaginal bleeding)none microscopic only intermittent gross bleeding, no clots persistent gross bleeding or clots; may require catheterization or instrumentation, or transfusion open surgery or necrosis or deep bladder ulceration Hemoptysis none mild without transfusion -requiring transfusion catastrophic bleeding, requiring major non- elective intervention Hemorrhage/bleeding associated with surgery none mild without transfusion -requiring transfusion catastrophic bleeding, requiring major non- elective intervention Note: Expected blood loss at the time of surgery is not graded as an adverse event. Melena/GI bleeding none mild without transfusion -requiring transfusion catastrophic bleeding, requiring major non- elective intervention Adverse Event01234 Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)none rare petechiae of skin petechiae or purpura in dependent areas of skin generalized petechiae or purpura of skin or petechiae of any mucosal site - Rectal bleeding/ hematochezia none mild without transfusion or medication persistent, requiring medication (e.g., steroid suppositories) and/or break from radiation treatment requiring transfusion catastrophic bleeding, requiring major non- elective intervention Vaginal bleeding none spotting, requiring <2 pads per day requiring ≥2 pads per day, but not requiring transfusion requiring transfusion catastrophic bleeding, requiring major non- elective intervention Hemorrhage - Other (Specify site, ___________)none mild without transfusion -requiring transfusion catastrophic bleeding, requiring major non- elective intervention HEPATIC Alkaline phosphatase WNL>ULN - 2.5 x ULN>2.5 - 5.0 x ULN>5.0 - 20.0 x ULN>20.0 x ULN Bilirubin WNL>ULN - 1.5 x ULN>1.5 - 3.0 x ULN>3.0 - 10.0 x ULN>10.0 x ULN Bilirubin associated with graft versus host disease (GVHD) for BMT studies, if specified in the protocol. normal≥2 - <3 mg/100 mL≥3 - <6 mg/100 mL≥6 - <15 mg/100 mL≥15 mg/100 mL GGT (γ - Glutamyl transpeptidase) WNL>ULN - 2.5 x ULN>2.5 - 5.0 x ULN>5.0 - 20.0 x ULN>20.0 x ULN Hepatic enlargement absent--present- Note: Grade Hepatic enlargement only for treatment related adverse event including Veno-Occlusive Disease. Hypoalbuminemia WNL Liver dysfunction/ failure (clinical) normal--asterixis encephalopathy or coma Portal vein flow normal-decreased portal vein flow reversal/retrograde portal vein flow - SGOT (AST) (serum glutamic oxaloacetic transaminase) WNL>ULN - 2.5 x ULN>2.5 - 5.0 x ULN>5.0 - 20.0 x ULN>20.0 x ULN SGPT (ALT) (serum glutamic pyruvic transaminase) WNL>ULN - 2.5 x ULN>2.5 - 5.0 x ULN>5.0 - 20.0 x ULN>20.0 x ULN Hepatic - Other (Specify, __________)none mild moderate severe life-threatening or disabling INFECTION/FEBRILE NEUTROPENIA Catheter-related infection none mild, no active treatment moderate, localized infection, requiring local or oral treatment severe, systemic infection, requiring IV antibiotic or antifungal treatment or hospitalization life-threatening sepsis (e.g., septic shock) Adverse Event01234 Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection)none--Present Life-threatening sepsis (e.g., septic shock) (ANC <1.0 x 109/L, fever ≥38.5°C) Also consider Neutrophils. Note: Hypothermia instead of fever may be associated with neutropenia and is graded here. Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia none--present life-threatening sepsis (e.g., septic shock) (ANC <1.0 x 109/L) Also consider Neutrophils. Notes:Hypothermia instead of fever may be associated with neutropenia and is graded here. In the absence of documented infection grade 3 or 4 neutropenia with fever is graded as Febrile neutropenia. Infection with unknown ANC none--present life-threatening sepsis (e.g., septic shock) Note: This adverse event criterion is used in the rare case when ANC is unknown. Infection without neutropenia none mild, no active treatment moderate, localized infection, requiring local or oral treatment severe, systemic infection, requiring IV antibiotic or antifungal treatment, or hospitalization life-threatening sepsis (e.g., septic shock) Also consider Neutrophils. Wound-infectious is graded in the DERMATOLOGY/SKIN category. Infection/Febrile Neutropenia - Other (Specify, __________)none mild moderate severe life-threatening or disabling LYMPHATICS Lymphatics normal mild lymphedema moderate lymphedema requiring compression; lymphocyst severe lymphedema limiting function; lymphocyst requiring surgery severe lymphedema limiting function with ulceration Lymphatics - Other (Specify, __________)none mild moderate severe life-threatening or disabling METABOLIC/LABORATORY Acidosis (metabolic or respiratory)normal pH threatening physiologic consequences Alkalosis (metabolic or respiratory)normal pH >normal, but ≤7.5-pH >7.5pH >7.5 with life- threatening physiologic consequences Amylase WNL>ULN - 1.5 x ULN>1.5 - 2.0 x ULN>2.0 - 5.0 x ULN>5.0 x ULN Bicarbonate WNL Adverse Event01234 CPK (creatine phosphokinase) WNL>ULN - 2.5 x ULN>2.5 - 5 x ULN>5 - 10 x ULN>10 x ULN Hypercalcemia WNL>ULN - 11.5 mg/dL >ULN - 2.9 mmol/L >11.5 - 12.5 mg/dL >2.9 - 3.1 mmol/L >12.5 - 13.5 mg/dL >3.1 - 3.4 mmol/L >13.5 mg/dL >3.4 mmol/L Hypercholesterolemia WNL>ULN - 300 mg/dL >ULN - 7.75 mmol/L >300 - 400 mg/dL >7.75 - 10.34 mmol/L >400 - 500 mg/dL >10.34 - 12.92 mmol/L >500 mg/dL >12.92 mmol/L Hyperglycemia WNL>ULN - 160 mg/dL >ULN - 8.9 mmol/L >160 - 250 mg/dL >8.9 - 13.9 mmol/L >250 - 500 mg/dL >13.9 - 27.8 mmol/L >500 mg/dL >27.8 mmol/L or acidosis Hyperkalemia WNL>ULN - 5.5 mmol/L>5.5 - 6.0 mmol/L>6.0 - 7.0 mmol/L>7.0 mmol/L Hypermagnesemia WNL>ULN - 3.0 mg/dL >ULN - 1.23 mmol/L ->3.0 - 8.0 mg/dL >1.23 - 3.30 mmol/L >8.0 mg/dL >3.30 mmol/L Hypernatremia WNL>ULN - 150 mmol/L>150 - 155 mmol/L>155 - 160 mmol/L>160 mmol/L Hypertriglyceridemia WNL>ULN - 2.5 x ULN>2.5 - 5.0 x ULN>5.0 - 10 x ULN>10 x ULN Hyperuricemia WNL>ULN - ≤10 mg/dL ≤0.59 mmol/L without physiologic consequences ->ULN - ≤10 mg/dL ≤0.59 mmol/L with physiologic consequences >10 mg/dL >0.59 mmol/L Also consider Tumor lysis syndrome, Renal failure, Creatinine, Hyperkalemia. Hypocalcemia WNL 1.75 - < 2.0 mmol/L 6.0 - < 7.0 mg/dL 1.5 - <1.75 mmol/L <6.0 mg/dL <1.5 mmol/L Hypoglycemia WNL 2.2 - < 3.0 mmol/L 30 - <40 mg/dL 1.7 - < 2.2 mmol/L <30 mg/dL <1.7 mmol/L Hypokalemia WNL Hypomagnesemia WNL 0.4 - <0.5 mmol/L 0.7 - <0.9 mg/dL 0.3 - <0.4 mmol/L <0.7 mg/dL <0.3 mmol/L Hyponatremia WNL Hypophosphatemia WNL ≥0.6 - <0.8 mmol/L ≥1.0 - <2.0 mg/dL ≥0.3 - <0.6 mmol/L <1.0 mg/dL <0.3 mmol/L Hypothyroidism is graded in the ENDOCRINE category. Lipase WNL>ULN - 1.5 x ULN>1.5 - 2.0 x ULN>2.0 - 5.0 x ULN>5.0 x ULN Metabolic/Laboratory -Other (Specify, __________)none mild moderate severe life-threatening or disabling MUSCULOSKELETAL Arthralgia is graded in the PAIN category. Arthritis none mild pain with inflammation, erythema or joint swelling but not interfering with function moderate pain with inflammation, erythema, or joint swelling interfering with function, but not interfering with activities of daily living severe pain with inflammation, erythema, or joint swelling and interfering with activities of daily living disabling Adverse Event01234 Muscle weakness (not due to neuropathy)normal asymptomatic with weakness on physical exam symptomatic and interfering with function, but not interfering with activities of daily living symptomatic and interfering with activities of daily living bedridden or disabling Myalgia [tenderness or pain in muscles] is graded in the PAIN category. Myositis (inflammation/damage of muscle)none mild pain, not interfering with function pain interfering with function, but not interfering with activities of daily living pain interfering with function and interfering with activities of daily living bedridden or disabling Also consider CPK. Note: Myositis implies muscle damage (i.e., elevated CPK). Osteonecrosis (avascular necrosis)none asymptomatic and detected by imaging only symptomatic and interfering with function, but not interfering with activities of daily living symptomatic and interfering with activities of daily living symptomatic; or disabling Musculoskeletal - Other (Specify, __________)none mild moderate severe life-threatening or disabling NEUROLOGY Aphasia, receptive and/or expressive, is graded under Speech impairment in the NEUROLOGY category. Arachnoiditis/meningismus/ radiculitis absent mild pain not interfering with function moderate pain interfering with function, but not interfering with activities of daily living severe pain interfering with activities of daily living unable to function or perform activities of daily living; bedridden; paraplegia Also consider Headache, Vomiting, Fever. Ataxia (incoordination)normal asymptomatic but abnormal on physical exam, and not interfering with function mild symptoms interfering with function, but not interfering with activities of daily living moderate symptoms interfering with activities of daily living bedridden or disabling CNS cerebrovascular ischemia none--transient ischemic event or attack (TIA) permanent event (e.g., cerebral vascular accident) CNS hemorrhage/bleeding is graded in the HEMORRHAGE category. Cognitive disturbance/ learning problems none cognitive disability; not interfering with work/school performance; preservation of intelligence cognitive disability; interfering with work/school performance; decline of 1 SD (Standard Deviation) or loss of developmental milestones cognitive disability; resulting in significant impairment of work/school performance; cognitive decline >2 SD inability to work/frank mental retardation Adverse Event01234 Confusion normal confusion or disorientation or attention deficit of brief duration; resolves spontaneously with no sequelae confusion or disorientation or attention deficit interfering with function, but not interfering with activities of daily living confusion or delirium interfering with activities of daily living harmful to others or self; requiring hospitalization Cranial neuropathy is graded in the NEUROLOGY category as Neuropathy-cranial. Delusions normal--present toxic psychosis Depressed level of consciousness normal somnolence or sedation not interfering with function somnolence or sedation interfering with function, but not interfering with activities of daily living obtundation or stupor; difficult to arouse; interfering with activities of daily living coma Note: Syncope (fainting) is graded in the NEUROLOGY category. Dizziness/lightheadedness none not interfering with function interfering with function, but not interfering with activities of daily living interfering with activities of daily living bedridden or disabling Dysphasia, receptive and/or expressive, is graded under Speech impairment in the NEUROLOGY category. Extrapyramidal/ involuntary movement/ restlessness none mild involuntary movements not interfering with function moderate involuntary movements interfering with function, but not interfering with activities of daily living severe involuntary movements or torticollis interfering with activities of daily living bedridden or disabling Hallucinations normal--present toxic psychosis Headache is graded in the PAIN category. Insomnia normal occasional difficulty sleeping not interfering with function difficulty sleeping interfering with function, but not interfering with activities of daily living frequent difficulty sleeping, interfering with activities of daily living - Note: This adverse event is graded when insomnia is related to treatment. If pain or other symptoms interfere with sleep do NOT grade as insomnia. Irritability (children <3 years of age)normal mild; easily consolable moderate; requiring increased attention severe; inconsolable- Leukoencephalopathy associated radiological findings none mild increase in SAS (subarachnoid space) and/or mild ventriculomegaly; and/or small (+/- multiple) focal T2 hyperintensities, involving periventricular white matter or <1/3 of susceptible areas of cerebrum moderate increase in SAS; and/or moderate ventriculomegaly; and/or focal T2 hyperintensities extending into centrum ovale; or involving 1/3 to 2/3 of susceptible areas of cerebrum severe increase in SAS; severe ventriculomegaly; near total white matter T2 hyperintensities or diffuse low attenuation (CT); focal white matter necrosis (cystic) severe increase in SAS; severe ventriculomegaly; diffuse low attenuation with calcification (CT); diffuse white matter necrosis (MRI) Memory loss normal memory loss not interfering with function memory loss interfering with function, but not interfering with activities of daily living memory loss interfering with activities of daily living amnesia Adverse Event01234 Mood alteration-anxiety, agitation normal mild mood alteration not interfering with function moderate mood alteration interfering with function, but not interfering with activities of daily living severe mood alteration interfering with activities of daily living suicidal ideation or danger to self Mood alteration-depression normal mild mood alteration not interfering with function moderate mood alteration interfering with function, but not interfering with activities of daily living severe mood alteration interfering with activities of daily living suicidal ideation or danger to self Mood alteration-euphoria normal mild mood alteration not interfering with function moderate mood alteration interfering with function, but not interfering with activities of daily living severe mood alteration interfering with activities of daily living danger to self Neuropathic pain is graded in the PAIN category. Neuropathy-cranial absent-present, not interfering with activities of daily living present, interfering with activities of daily living life-threatening, disabling Neuropathy-motor normal subjective weakness but no objective findings mild objective weakness interfering with function, but not interfering with activities of daily living objective weakness interfering with activities of daily living paralysis Neuropathy-sensory normal loss of deep tendon reflexes or paresthesia (including tingling) but not interfering with function objective sensory loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living sensory loss or paresthesia interfering with activities of daily living permanent sensory loss that interferes with function Nystagmus absent present---Also consider Vision-double vision. Personality/behavioral normal change, but not disruptive to patient or family disruptive to patient or family disruptive to patient and family; requiring mental health intervention harmful to others or self; requiring hospitalization Pyramidal tract dysfunction (e.g., ↑ tone, hyperreflexia, positive Babinski, ↓ fine motor coordination)normal asymptomatic with abnormality on physical examination symptomatic or interfering with function but not interfering with activities of daily living interfering with activities of daily living bedridden or disabling; paralysis Seizure(s)none-seizure(s) self-limited and consciousness is preserved seizure(s) in which consciousness is altered seizures of any type which are prolonged, repetitive, or difficult to control (e.g., status epilepticus, intractable epilepsy) Speech impairment (e.g., dysphasia or aphasia)normal-awareness of receptive or expressive dysphasia, not impairing ability to communicate receptive or expressive dysphasia, impairing ability to communicate inability to communicate Syncope (fainting)absent--present-Also consider CARDIOVASCULAR (ARRHYTHMIA), Vasovagal episode, CNS cerebrovascular ischemia. 医院药品不良反应监测小组机构及工作职责 一、机构 1、药物不良反应监测领导小组成员 组长: 副组长: 成员: 相关科室专家: 联系电话: 联系人: 2、各科室不良反应监测员:各科大组长及护士长 二、药物不良反应监测小组任务 药物不良反应监测小组任务是对我院药物不良反应监测工作进行业务技术指导,收集、整理、分类、保管与评价不良反应病例报告资料,反馈不良反应信息,并在药品安全性方面负责向药品监测管理部门咨询。 三、药物不良反应监测小组工作职责 1、向本院医护人员宣传药物不良反应监测工作的重要意义并解释有关问题。 2、密切关注本院药品不良反应动向,并督促医护人员认真填写不良反应报告表,特别注意新药不良反应的发生,不论轻、重度,只要认为可疑都应及时报告。 3、负责指导和督促药物不良反应监测员的工作。 4、不定期对本院严重或疑难药物不良反应病例进行因果关系评价,因果关系评价会聘请相关科室专家参加。 四、药物不良反应监测员工作职责 1、负责本科室药品不良反应病历的收集工作。 2、督促主管医生护士正确填写不良反应报告表,报告表中各项应无漏项,合格后送交药剂科临床药学室。 3、应本着“可疑就报”的原则,及时向临床药学室通报本科室药品不良反应情况,每年每个科室向临床药学室报告本科室药物不良反应报告表≧10份,若有漏报,按药品不良反应监测管理办法给予处罚。 五、药物不良反应专家组工作职责 1、负责评价本院收集的不良反应病例。 2、对药物不良反应工作进行业务、技术指导。 六、临床药学组工作职责 1、负责医院药品不良反应监测工作的组织、协调工作。 2、负责收集、整理、分类、保管、评价上报的药品不良反应报告。 3、负责药品不良反应信息交流与反馈工作。 药品不良反应/ 事件报告表 首次报告□ 跟踪报告□ 编码： 报告类型：新的□ 严重□ 一般□ 报告单位类别：医疗机构□ 经营企业□ 生产企业□ 个人□ 不良反应事件名称：不良反应事件发生时间：年月日不良反应/ 事件过程描述（包括症状、体征、临床检验等）及处理情况（可附页） 不良反应/ 事件的结果：痊愈□好转□ 未好转□ 不详□ 有后遗症□ 表现： 死亡□ 直接死因：死亡时间：年月日 停药或减量后，反应/ 事件是否消失或减轻？是□ 否□不明□ 未停药或未减量□再次使用可疑药品后是否再次出现同样反应/ 事件？是□ 否□ 不明□ 未再使用□ 电子邮箱： 签名：××× 药 品 不 良 反 应 / 事 件 报 告 表示例 不良反应 / 事件过程描述（包括症状、体征、临床检验等）及处理情况（可附页） 一般格式为：患者因×××疾病于×××月×××日（必要时应详细到×××时分）以×××途径给予×××药品，×××剂量，用药×× ×时间出现×××反应（反应描述须明确、具体） ，×××时间后给予是否停药及×××处理（包括以×××途径给予×××药品及×××剂 和其他处理措施） ，处理后×××时间患者转归情况。 对原患疾病的影响： 不明显□ 病程延长□ 病情加重□ 导致后遗症□ 导致死亡□ 报告人评价： 肯定□ 很可能□ 可能□ 可能无关□ 待评价□ 无法评价□ 签名：××× 报告单位评价： 肯定□ 很可能□ 可能□ 可能无关□ 待评价□ 无法评价□ 签名：××× 报告人信息 患者姓名：××× 性别：男□女□ 出生日期： 年 月 日 或年龄： ×× 民族：×× 体重（ kg ）：×× 联系方式：×××××× 原患疾病：指患者此次入 诊的主要疾病（如果有多 疾病可以补充在相关重要 是备注里面），不能写字 院或就 种慢性 信息或 母缩写。 医院名称：三亚市中医院 病历号 / 门诊号：××××（务必 填写） 既往药品不良反应 / 事件：有□需提供药品通用名称及具体反应 无□ 不详□ 家族药品不良反应 / 事件：有□需提供药品通用名称及具体反应 无□ 不详□ 报告单位类别：医疗机构□ 其他□ 相关重要信息： 吸烟史□ 饮酒史□ 妊娠期□ 肝病史□ 肾病史□ 过敏史□此处是提供有否食物等过敏史 首次报告□ 跟踪报告□ 报告类型：新的□ 严重□ 一般□ 编码： 经营企业□ 生产企业□ 个人□ 其他□ 药 品 批准文号 商品 名称 通用名称 （含剂型） 生产厂 家 生产批号 用法用量 （次剂量、 途径、 日次数） 用药起止时 间 用药原因 怀 疑 药 品 国药准字 此处填写药品的 通用名 称。注射剂 包含注射液和粉 针剂，请认真选择 正确剂型 本次使用药 物的生产批 号 包括每次用药剂 量、 给药途径、 每日给药 次数， 例如，5mg ， 口服， 每日 2 次。 指使用药品 的同 一剂量 的开始时 间 和停止时间 填写使用该药品的原因，应详 细填 写。例如：患者高血压病 史，此次因肺部感染而注射氨 苄青霉素引起不良反应，用药 原因栏应填写肺部 感染 并 用 药 品 同上 量， 不良反应 / 事件的结果：痊愈□ 死亡□ 好转□ 直接死因： 未好转□ 不详□ 有后遗症□ 表现： 死亡时间：× 年 × 月 × 日 停药或减量后，反应 / 事件是否消失或减轻？ 再次使用可疑药品后是否再次出现同样反应 / 事件？ 是□ 否□ 是□ 否□ 不明□ 不明□ 未停药或未减量□ 未再使用□ 关联性评价 联系电话：务必正确填写 职业：医生□ 药师□ 护士□ 其他□ 不良反应 / 事件名称：应填写不良反应中最主要、最明显的症状。 不良反应 / 事件发生时间：× 年 × 月× 日（应填写发生不良反应 / 事件 的确切时间） 精神科常用药物作用、不良反应 抗精神病药：是治疗精神病性症状的药物，临床上主要用于治疗精神分裂症或其它重性精神病，也称为强安定剂、神经阻滞剂。 不良反应及相应处理 1、常见副作用：口干、舌燥、鼻堵、乏力、思睡、心动过速、锥体外系反应。罕见副作用：阻塞性黄疸、粒细胞缺乏、视网膜色素沉着。其中以急性黄疸、粒细胞缺乏症、癫痫样发作、剥脱性皮炎、肝损害及低血压性休克最为严重，应高度重视！ 2、原则上凡是在治疗过程中出现的各种不适和躯体改变，均应考虑是否与药物有关，通过减药或停药对此有鉴别和治疗意义。一般而言，抗精神病药无成瘾性，但可能产生躯体依赖。 不良反应具体划为几个方面 1、精神方面的不良反应 （1）过度镇静：无力、思睡，尤以氯丙嗪、氯氮平常见。 （2）药源性精神副作用：如意识障碍、消极忧郁、幻觉、躯体性妄想、缄默、紧样状态、兴奋躁动等。 药源性精神副作用：精神运动性兴奋表现为焦虑不安、激动、凶狠、敌意、极度兴奋和冲动、攻击行为，常为一过性，多见于治疗初期。不需特殊处理。 药源性精神副作用：意识障碍 意识障碍出现的程度不同，由意识模糊或梦幻样状态到谵妄状态。表现：定向力障碍、言语散漫、错觉、幻觉、兴奋躁动、刻板动作或冲动行为、生活不能自理。可伴脉速、出汗、震颤、构音不清、扩瞳等躯体症状。多见于：用药早期；大剂量用药或在剧增、骤停或更换药物时；联合用药；老年人、有脑器质性病变或躯体疾病者。处理主要为减药或停药。 药源性精神副作用：药源性抑郁状态 发生率依次为利血平、氟哌啶醇、氯丙嗪、奋乃静、三氟拉嗪。处理：及时减药、停药或加服抗抑郁药，严密观察以防意外。 药源性精神副作用：紧综合征 症状：缄默、木僵、违拗、蜡样屈曲，重者吞咽困难、生活不能自理，可出现神经系统体征，如腱反射亢进、膝踝痉挛、震颤等。处理：酌情减药、停药或加用抗帕金森药。 （3）惊厥：任一种酚噻嗪衍生物都可能诱发癫痫发作，以高剂量、低效价的氯丙嗪、氯氮平为多。处理方法：加药宜慢，可加用抗癫痫药如苯妥英钠，必要时减药、停药或换药，排除器质性疾患。 常见药物不良反应 精神科常用药物作用、不良反应 抗精神病药：是治疗精神病性症状的药物，临床上主要用于治疗精神分裂症或其它重性精神病，也称为强安定剂、神经阻滞剂。 不良反应及相应处理 1、常见副作用：口干、舌燥、鼻堵、乏力、思睡、心动过速、锥体外系反应。罕见副作用：阻塞性黄疸、粒细胞缺乏、视网膜色素沉着。其中以急性黄疸、粒细胞缺乏症、癫痫样发作、剥脱性皮炎、肝损害及低血压性休克最为严重，应高度重视！ 2、原则上凡是在治疗过程中出现的各种不适和躯体改变，均应考虑是否与药物有关，通过减药或停药对此有鉴别和治疗意义。一般而言，抗精神病药无成瘾性，但可能产生躯体依赖。 不良反应具体划为几个方面 1、精神方面的不良反应 （1）过度镇静：无力、思睡，尤以氯丙嗪、氯氮平常见。 （2）药源性精神副作用：如意识障碍、消极忧郁、幻觉、躯体性妄想、缄默、紧张样状态、兴奋躁动等。 药源性精神副作用：精神运动性兴奋表现为焦虑不安、激动、凶狠、敌意、极度兴奋和冲动、攻击行为，常为一过性，多见于治疗初期。不需特殊处理。 药源性精神副作用：意识障碍 意识障碍出现的程度不同，由意识模糊或梦幻样状态到谵妄状态。表现：定向力障碍、言语散漫、错觉、幻觉、兴奋躁动、刻板动作或冲动行为、生活不能自理。可伴脉速、出汗、震颤、构音不清、扩瞳等躯体症状。多见于：用药早期；大剂量用药或在剧增、骤停或更换药物时；联合用药；老年人、有脑器质性病变或躯体疾病者。处理主要为减药或停药。 药源性精神副作用：药源性抑郁状态 发生率依次为利血平、氟哌啶醇、氯丙嗪、奋乃静、三氟拉嗪。处理：及时减药、停药或加服抗抑郁药，严密观察以防意外。 药源性精神副作用：紧张综合征 症状：缄默、木僵、违拗、蜡样屈曲，重者吞咽困难、生活不能自理，可出现神经系统体征，如腱反射亢进、膝踝痉挛、震颤等。处理：酌情减药、停药或加用抗帕金森药。 （3）惊厥：任一种酚噻嗪衍生物都可能诱发癫痫发作，以高剂量、低效价的氯丙嗪、氯氮平为多。处理方法：加药宜慢，可加用抗癫痫药如苯妥英钠，必要时减药、停药或换药，排除器质性疾患。 10 / 1 常见药物不良反应 （4）锥体外系反应（EPS）：有五种表现形式1）药源性帕金森氏综合征：四个特征：运动不能、肌肉强劲、震颤、植物神经功能紊乱。2）静坐不能。3）急性肌张力障碍。以上三种锥体外系反应均可减药、停药、合用对抗药。4）迟障（TD）：处理：减、停、换药。停抗胆碱能药；对症治疗选用多巴胺耗竭剂,多巴胺阻滞剂；抗组胺药非那根；促大脑代谢药；抗焦虑药安定。说明：TD重在预防。5）兔唇综合征：停药可消失，抗震颤麻痹药可能有效。 （5）植物神经系统：轻的不必处理，如症状持续发展并渐趋严重，则可能出现抗胆碱能中毒综合征或抗胆碱能危象。此时应停药，可用毒扁豆碱1-2mg肌注。恶性综合征：临床表现为显著的帕金森氏综合征，植物神经功能紊乱，可伴高热、意识障碍，可能与药物锥体外系反应和体 常见药物不良反应的一般规律及特点 药品不良反应(ADR)是指药品在正常用法用量下出现的与用药目的无关或意外的有害反应，以下是搜集整理的常见药物不良反应一般规律探究的论文范文，供大家阅读查看。 上世纪60年代初期发生的震惊世界的“反应停”事件，使许多国家都意识到药物不良反应监测在临床用药中的重要性。随着大量高效、高选择性和治疗剂量范围窄的药物不断上市，且联合用药机会大大增加，使药物不良反应的发生率不断增加，这也使ADR日益引起人们的关注。开展药物不良反应工作的目的就是要通过药物监测提高广大医务人员对安全合理用药的重视，定期分析导致ADR发生的因素，尽量减少和避免药品不良反应的发生[2]。作为一所三甲医院，来我院就诊的患者人数众多，因此，明确开展ADR监测，对促进安全合理用药，减少药物不良反应造成的药源性疾病对人们身体健康的危害是非常必要的。本文对我院2012年1月1日-2012年12月31日上报的568例有效ADR报告表进行统计分析，探讨常见药物不良反应的一般规律及特点，为临床合理用药提供参考。 1资料与方法 1.1资料查阅我院于2012年1月1日-12月31日报告ADR共568例。 1.2方法采用回顾性调查法分别按患者年龄、药物剂型及给药途径、药物种类、ADR累及器官或系统以及临床表现进行统计分析。 2结果 2.1患者年龄与ADR发生的关系从年龄分布来看大于60岁老 人(180例，占31.69%)和小于14岁儿童(103例，占18.13%)是发 生不良反应的主要人群，两者共占发生ADR的一半(共283例);且 是发生严重或新的药物不良反应的重点人群(严重或新的ADR共10例，占71.43%)。见表1。 2.2给药途径与ADR发生的关系通过对不同给药途径的分析发现，引起ADR发生最多的为静脉给药(占72.89%)，口服和其它给 药方式占较小的比例。其中静脉滴注给药有8例发生严重不良反应，2例新的一般不良反应;口服给药有3例发生严重不良反应，1例新的一般不良反应。见表2。 2.3药物种类与ADR发生的关系通过对药物所属类别进行分类统计得出，568例ADR报告中涉及多类别药物，ADR发生率最高的 药物为抗菌药物(排名前20位中占8个品种)，其次为中药注射剂 和抗肿瘤药物及生物制剂。抗菌药物中青霉素和头孢菌素类不良 反应发生例数最多，占据前三位，分别是阿洛西林(30例)、头孢 呋辛(20例)、头孢他啶(19例)。见表3。 2.4ADR累及的器官或系统及临床表现对ADR累及的器官或系 药品不良反应知识 药物是人们与疾病作斗争的重要武器，它具有两重性，一方面是预防和治疗疾病的重要手段，另一方面它又可能引起一些不良反应，甚至导致另一些疾病。能够引起不良反应的药物专门多，按其来源分类，可包括植物药、动物药、矿物药、抗生素、生物制品、人工合成药、中成药等；假如按照药理作用分类，其几乎能够包括迄今为止临床应用中所有类不的药物。 药品不良反应可侵及人体的各个器官和系统，包括呼吸系统、循环系统、消化系统、血液系统、神经、精神系统等等，以及致突变、癌变和畸形等。 药品不良反应具有自限性特点，发觉早，处理及时，大部分患者都能够自行恢复。假如差不多出现了严峻反应甚至阻碍到人体的组织器官功能，除停药外，还应及时进行对症处理和治疗。 了解和学习有关药品不良反应的相关知识，加强医务人员和患者 在用药过程中的监控意识，是保证安全合理用药，提高医疗质量的重要环节。 一、药品不良反应差不多概念 （一）药品不良反应的定义 药品不良反应（Adverse Drug Reactions，简称ADR）要紧是指合格的药品在预防、诊断、治疗疾病的过程中，在正常用法、用量情况下出现的与用药目无关的有害反应。这些反应不同程度地损害着人体健康，甚至危及生命。 严格地讲，ADR要紧是指常规剂量下出现与治疗目的无关的有害反应；而广义的药品不良反应还应包括超剂量给药、意外给药、蓄意给药、药物治疗错误、药物滥用、药物相互作用引起的各种不良后果。据此，药品不良反应的判定必须具有以下三点： 第一、药品必须是合格的。所谓合格药品，指的是符合我国《药品治理法》和国家药品标准并经药品监督治理部门批准生产的药品。假药、劣药产生的不良后果不属于药品不良反应范畴。 第二、患者使用药品和医师指导用药必须符合药品讲明书的规定或没有违反药品的配伍禁忌以及用法用量。误用、滥用药物所造成的后果不属于药品不良反应。 第三、药品不良反应的发生与用药目的无关或出乎事先预料。 药品不良反应报告和监测管理制度 1 目的 建立药品不良反应报告和监测管理制度保证该项工作有序、按时、准确完成。 2 依据 《药品经营质量管理规》、《药品不良反应报告和监测管理办法》及公司相关制度。 3 适用围 适用于公司所经营药品的不良反应监测、报告、处理、跟踪。 4职责 运营中心、质管中心对本制度的实施负责。 5容 5.1药品不良反应报告和监测管理要求 5.1.1公司各部门在经营过程中获知或者发现可能与用药有关的不良反应，应当及时向质管中心报告，由质管员通过国家药品不良反应监测信息网络报告；报告容应当真实、完整、准确。 5.1.2公司各部门应当配合药品监督管理部门、卫生行政部门和药品不良反应监测机构对药品不良反应或者群体不良事件的调查，并提供调查所需的资料。 5.1.3质管中心质管员应当建立并保存药品不良反应报告和监测档案，记录的药品不良反应信息应包括以下容：药品名称、规格、批号、包装规格；客户名称、负责人、投诉人和联系；使用不良反应药品的患者（和联系方式、患者名称、年龄）；药品不良反应的临床表现与过程；患者的用药情况等。 5.1.4质管中心质管员应当对收集到的药品不良反应报告和监测资料进行分析和评价，并及时上报质量负责人采取有效措施减少和防止药品不良反应的重复发生。质管中心调查处理方法如下: （1）调查产品的购销渠道，核实物流在途情况、往来单位仓储情况，初步的临床用药情况并记录； （2）核查该产品的购、销、存记录，冷链药品的还应核实在途在库的温湿度监测情况，作为调查的凭证； （3）对于确定为公司销售的药品产生不良反应的，应及时采取有效的处理措施，需要召回的及时下达召回通知按照《药品召回管理制度》执行；（4）对于超出公司质管中心调查处理能力畴的应及时报品监督管理部门、卫生行政部门和药品不良反应监测机构，并协助其进行相关调查处理。 5.2基础术语 5.2.1药品不良反应，是指合格药品在正常用法用量下出现的与用药目的无关的有害反应。 5.2.2药品不良反应报告和监测，是指药品不良反应的发现、报告、评价和控制的过程。 5.2.3严重药品不良反应，是指因使用药品引起以下损害情形之一的反应：（1）导致死亡； 药物的不良反应及分类 摘要对现行药理学教材中药物不良反应的概念作对照分析,提出使用合适的药物不良反应概念及其分类方法。 关键词药物不良反应;分类 药物不良反应的概念在不同版本的书籍上几乎都是指”对防治疾病无益甚至有害的反应”,这个概念一直沿用了十几年,虽然WHO国际药物监测合作中心早已下了明确的定义,就是指”在预防、诊断、治疗疾病或调节生理机能过程中,人接受正常剂量的药物时出现的任何有害的和与用药目的无关的反应”。国家食品药品监督管理局对药物不良反应有严格定义及分类,根据1999年《药品不良反应监测管理办法(试行)》第五章附则第二十八条规定:药品不良反应主要是指合格药品在正常用法用量下出现的与用药目的无关的或意外的有害反应。 药物的分类方法也不统一,有的书籍上包括副作用、毒性作用、后遗效应、过敏反应、继发反应、特异质等;有的又根据1977年Rawlins和Thompson设计的ADRs分类法,即将其分为A、B两类反应。A类反应指因某种药物正常的药理作用过强而引起的反应,如普萘洛尔引起的心动过缓。这些反应可根据药物的药理学特性预知,通常呈剂量依赖型。此类反应较常见,发病率较高但死亡率较低。B类反应指与药物正常药理作用无关的、新的或异常的不良反应,如青霉素引起的过敏反应,通常不可预知,也不常见,发病率较低但死亡率相对较高。也有的分为与药理作用相关类如副反应、与机体反应相关类如过敏反应、与连续用药相关类如耐受性。各种教学用书及参考资料上对不良反应究竟包括哪些,几乎没有一致的。 药物不良反应的概念应该使用我国《药品不良反应监测管理办法(试行)》第五章附则第二十八条规定的概念。这个概念和我们教材上的概念的主要区别是强调了正常剂量和正常用法。也就是说,这种定义排除了意外的过量用药或用药不当所导致的不良反应。如用错药物及剂量、滥用药物、自杀性过量服药等不包括在内。如果药物不良反应的概念做了调整,那么药物不良反应的类型或分类也应该做调整。毒性作用、后遗效应、继发反应、首剂效应、撤药反应、依赖性应该归到副反应里。过敏反应和特异质就属于意外的有害反应。从上述WHO和我国药品监督部门对药物不良反应的定义来看药物的不良反应:①强调不符合用药目的;②强调反应对机体的损害程度。轻的就是不符和用药目的,重的就是意外的有害反应或有害反应。实际上不良反应也肯定有轻有重。如果非要用副反应和毒性反应作为药物不良反应的一种,那么副反应和毒性反应就应该只是程度上的区别,这种区分有多大意义值得商榷。药物不量反应包括的内容很广泛,有的有交叉,对于初学者很难区分。使用糖皮质激素引起的肾上腺皮质功能低下是属于后遗效应呢,还是属于继发反应摸棱两可。后遗效应可能比较短暂,如服用巴比妥类催眠药后次晨的宿醉现象;也可能比较持久,如长期应用肾上腺皮质激素,一旦停药后肾 药品不良反应 篇一：药品不良反应概述 药品不良反应概述 第一节药品不良反应定义 广义的药品不良反应是指用药引起的任何不良情况。其中包括超剂量用药、意外给药、蓄意用药、药物滥用、药物相互作用所引起的不良后果。 WHO对药物不良反应的定义：在预防、诊断、治疗目的无关的反应。该定义排除了有意的或意外的过量用药或用药不当。 国家药品不良反应监测中心的定义：在正常用法用量情况下出现的与用药目的无关的或意外的有害反应。包括副作用、毒性作用、后遗效应、继发反应、过敏反应、特异性遗传素质等。与WHO对药品不良反应的定义一样，排除了有意的或意外的过量误用、药物滥用（包括吸毒）、不按规定方法使用药品等情况引起的责任性或刑事性事件。这种设定是为了便于监测报告制度的建立和工作的开展。 研究药物不良反应将有利于促进合理用药。临床合理用药必须掌握的两个要点即有效性和安全性。前者是指对症选药，即使所选药物的作用符合于治病的要求，后者是指避免或减少药物不良反应和药源性疾病的发生。 第二节药品不良反应分类 一药品不良反应按发病机制分类 不良反应的分类，揭示了药物与机体间的相互关系，使人们关注引起同类反应的共同因素和表现形式，从而采取相应的共同的措施进行治疗和预防。传统的分类方法通常把药物不良反应分为A型、B 型和C型三大类。这种简单明了的分类从1977年廷至今天，但因为粗略，不能准确地把各种不良反应的成因机制归于某类，因此就出现了目前新的、内容更丰富、定义更准确的分类方法，即A、B、C、D、E、F、G、H、U共九类。新的分类方法保留了A类，对B类则重新进行了定义和划分。 A型反应：又称为剂量相在的不良反应。它是药物常规药理作用的廷伸和发展，反应程度与药物在体内浓度高低密切相关，因此本型反应是可以预测的，在人群中发生率高，死亡率低。毒副作用是本型反应主要内容，其它还有过度反应、首剂反应、撤药反应、继发反应、药物依赖性等。 B型反应：又称质变异常性不良反应，它是一种与药物常规药理作用无关的异常反应，常规毒理筛选不能发现，难预测，发生率低而死亡率高。B型不良反应又可分为药物异常性和病人异常性两种，如特异性遗传素质反应，药物变态反应。 C型反应：一般在长期用药后出现，难以预测。其特点是：背景发生率高、非特异性、没有明确的时间关系、潜伏期长、不可重现。 有些药物反应难以用A型或B型反应来分类，如由于药物作用诱发的人体免疫功能低下而引起的患病率增加，药物引起三致作用、二 在一种新药或药品的新用途的临床试验中，其治疗剂量尚未确定时，所有有害而非所期望的、与药品应用有因果关系的反应，也应视为药品不良反应。 在药理学中，指某种药物导致的躯体及心理副反应、毒性反应、变态反应等非治疗所需的反应。可以是预期的毒副反应，也可以是无法预期的过敏性或特异性反应。在物质使用中，包括用药所致的不愉快的心理及躯体反应。 按正常用法、用量应用药物预防、诊断或治疗疾病过程中，发生与治疗目的无关的有害反应。其特定的发生条件是按正常剂量与正常用法用药，在内容上排除了因药物滥用、超量误用、不按规定方法使用药品及质量问题等情况所引起的反应。 定义凡用药后产生与用药目的不相符的并给病人带来不适或痛苦的反应统称为不良反应(adverse reaction)。药物的不良反应包括副作用(side effects)、毒性反应(toxic reaction)、变态反应(allergic reaction)、后遗效应(after effect)、继发效应(secondary effect)、特异质反应(idiosyncratic reaction)及三致(致癌carcinogenesis、致畸teratogenesis、致突变mutagenesis)作用。一般是可预知的，但有的是不可避免的，有的则是难以恢复的。 药物的后遗反应 指停药后的生物效应，例如服用巴比妥类药物，次日的宿醉现象，停药后可消失。氨基糖苷类抗生素引起耳蜗神经损害很难恢复，可成为永久性耳聋。过敏反应药物刺激机体而发生的不正常的免疫反应。药物在体内与高分子载体蛋白结合形成抗原，刺激机体产生抗体，药物再次进入机体发生抗原抗体反应导致过敏反应性疾病。 特异质反应少数人用药之后，会发生于药理作用无关的反应。多数是由于个体生化机制异常，比如缺乏某种药物代谢酶所形成依赖性喉，断药后体内不能维持正常生理机能，出现戒断综合征，有时很严重，可发生惊厥，甚至死亡。 药物的致畸作用 在妊娠期内，特别是头三个月胎儿器官形成期，此时某些药物可作用于胎儿而形成先天畸形。 药物的致癌作用 具有致癌作用的药物称致癌因子，不少化学药品属于此类物质。 药物的致突变作用 遗传因子DNA的构成发生突然变异和染色体异常，可引起此变异的因子称变异原。短时间内变异原通过机体内因起作用，发生显著的生物学变异，如畸胎或肿瘤的生成。 药物不良反应常见原因分析 药品是一种特殊商品，在防病治病、保障人民身体健康中起着至关重要的作用，市场经济条件下，受急功近利的物欲刺激影响，使临床合理用药，合理治疗的传统医德受到打击和挑战，临床治疗中的不合理用药，引发了众多的医源性不良反应，甚或引起医疗差错事故，现药品是一种特殊商品，在防病治病、保障人民身体健康中起着至关重要的作用，市场经济条件下，受急功近利的物欲刺激影响，使临床“合理用药，合理治疗”的传统医德受到打击和挑战，临床治疗中的不合理用药，引发了众多的医源性不良反应，甚或引起医疗差错事故，现将药物不良反应常见原因分析如下。 1.超量应用 某些药物其治疗量与中毒量非常接近，临床应用，有严格的规定，尤其是儿童，要严格按照公斤体重核算药物用量，稍有超量，就会出现严重的毒副作用，造成无可挽回的后果，如辽宁省某市中心医院，1997年7月在治疗急性肠炎患儿时，静脉点滴磷霉素钠，药物剂量超过正常量3倍，输液过程中，患儿出现腹痛，抽搐，最后因呼吸、循环衰竭死亡；另有报道，某个体诊所业主，无证行医，在为一婴儿治病时，超剂量用药，两种药品用量超出正常用量的10倍以上，导致患儿死亡，构成一级医疗事故。 2.药品质量不纯 药品质量不纯与其不良反应的发生关系密切。据李燮彬报道，青霉素精制品皮试阴性肌注后不良反应的发生率为0.20%,而一般正常品发生率为0.43%,统计学处理，差异有非常显着性，（P<0.01）。另外，抗生素制剂中有大量的微细结晶、聚合物或降解物，输液中的微粒异物可导致静脉炎，在输液装置上加“终端滤器”，可防止或减少静脉炎的发生；另据赵誉华报道，在21例静脉点滴丹参注射液出现的输液反应当中，送检9例，结果热原反应阳性者5例（占55%），并将同批号丹参注射液5盒（50支），按药典要求用3只家兔进行测定，结果初测和复测均显示热原阳性。 3.过敏反应 随着医药卫生事业的发展，越来越多的医药品种用于临床，引起过敏反应的药物种类逐渐增多。唐静怡等统计了一组病例，药典未规定需先行做过敏试验的药物中，有52种药物导致了过敏反应猝死；有些药物试验阴性而用药过程中出现反应；部分药品在常规做过敏试验时，即可发生过敏性休克，更需注意的是，某些抗过敏药物本身也能引起过敏反应。 4.给药方法不当 临床用药，有严格规定，违规操作，会增加副作用。据郑玲等报道，某心衰患者，护士未严格执行医嘱，将应该静脉点滴的维生素C7g未稀释直接静脉输入，5min后，患者局部剧烈疼痛，静脉沿线明显红肿、压痛，经硫酸镁湿敷了3d后红肿始退，但血管仍呈条索状硬化。 5.违反操作常规 医疗工作人命关天，须严肃认真，一丝不苟，每个环节的敷衍了事，马马虎虎，都会造成严重后果。据窦氏报道，某患儿行唇裂修补术，术前护士将吗啡误为阿托品而注射，造成中毒，幸抢救及时而获救；另一8个月的支气管炎患儿，医生处方氨茶碱20mg,每日3次口服，药房人员误将10mg1片的氨茶碱拿成100mg1片，且分装2袋，也未向患儿家属交待清楚，结果每次服每袋中2片，实际每次服用400mg,较原量大20倍，造成严重中毒；临床护理中，违反操作规程，同样会酿成恶果，唐静怡等曾报道了2例猝死病人，均系未严格执行“三查七对”制度，将药物用错病人所造成。 6.忽视某些药物排泄特点 某些药物，能通过乳汁排泄，忽视此等特点，会殃及乳儿。据窦氏报道，2例冬眠灵中毒的患儿皆系其母服用冬眠灵所致；另据潘月清报道，一足月顺产正常男婴的妇女，产后3个月内因放置节育环出现“子宫功能性出血”而服妇康片，每次4片，每日3次，连服1个月后，使本来毛发乌黑、发育正常的乳儿造成内分泌紊乱，从而出现毛发白色、皮肤干燥、不出汗、烦躁哭闹、食欲不振、睡眠等一系列类似西蒙综合症和早老症的现象。 7.忽视药物副作用 药品不良反应工作总结 2017年我院不断加大措施、健全组织、完善制度、强化督导,促进了药品不良反应监测工作的顺利开展,取得了一些成绩,为做好药品不良反应监测工作作出了积极努力,现总结如下: 一、加强领导明确任务 为了加强对我院药品不良反应监测报告工作顺利的开展,经我院院务会决定成立药品不良反应监测工作领导小组,小组由院长张广海担任组长,小组办公室设在本院,以此负责全院药品不良反应监测工作的组织、协调、督报工作。我院的药品不良反应监测工作,在领导小组的领导下,在年初就联合召开了会议,进行安排部署,将目标任务层层分解,切实做好药品不良反应监测数据的分析评价以及药品不良反应的宣传培训和信息的收集、上报工作,推动监测报告工作广泛、深入、扎实的展开。 二、健全组织,完善制度。 我院根据上级部门对药品不良反应的工作部署和领导要求,为确保我院药品不良反应监测工作的健康顺利开展,通过不断加强组织建设、制度建设和人员培训等三项措施,促进了全院监测工作正常运转,具体如下: 一是建立健全药品不良反应监测报告的体制和工作机制,成立药品不良反应监测领导小组,建立药品不良反应监测点;明确我院药品不良反应监测联络员,具体负责本院与上级不良反应检测中心的联系沟通工作,实行实时督报制度,各科室在规定日期集中报送监测信息,杜绝漏报、瞒报、不报现象。 二是建立药品不良反应监测信息员库,各信息员要做到反馈灵敏、报告及时,形成层层有人管、层层有人抓的良好 局面,使我院药品不良反应报告及监测工作再上新台阶。 三是加强培训,我院派负责药品不良反应监测信息收集工作的同志多次参加了市药监局组织的药品不良反应监测培训会议,同时又多次组织我院工作人员在全院大会上学习药不良反应的法律法规和相关知识,明确了开展药品不良反应报告和监测工作是医务工作者义不容辞的责任,通过这些有效措施,提高了他们的认识,丰富了专业知识,增强了对做好监测工作的使命感和责任心。 截止2017年12月,我院共上报不良反应检测病例3例,3例都是药品不良反应,完成了2017年的任务,同时,对各个监测点的信息上报情况进行了认真核,未发生一起漏报、瞒报、迟报现象,上报率达100%,做到了准确、科学、及时,而且不断提高了监测报告的质量和水平。 三、但还存在一定的问题: 1、对事件报告的“关联性”评价不够规范,可能和不可能等关联性评价混淆不清。 2、医学术语匮乏,在事件报告的描述中不会运用相关的医学术语去描述临床症状。 3、责任心不强。在事件报告表中,有些厂家的药品商品名和通用名是相同的,或者在商品名称的填写处填写成通用名 四、对药品不良反应工作中存在的问题，改进措施如下： 1、加强培训科室医务人员对药品不良反应事件监测的概 念,能准确定义不良反应事件,防止漏报。 2、对于科室隐瞒不报的药品不良反应事件,加大处罚力度，避免造成不良后果,一旦发生药品不良反应，须引起科 药品不良反应监测及报告制度 一、医院成立药品不良反应工作小组，由主管院长任组长，办公室设在药学部临床药学室。临床药学室负责全院药品不良反应的报告和监测管理。各科室指定一名不良反应监测员具体负责药品不良反应报告。药品不良反应工作小组的任务是组织、指导医院药品不良反应监测工作，对疑难、复杂的不良反应病例进行讨论复审，并向省ADR 监测中心报告。 二、从事药品不良反应报告和监测的工作人员应当具有医学、药学、流行病学或者统计学等相关专业知识，具备科学分析评价药品不良反应的能力。 三、药品不良反应报告和监测是药品不良反应的发现、报告、评价和控制的过程。无论是单一用药还是多药联用，均应遵循“可疑就报”的原则，对难以确定因果关系的，只要不能完全排除药品不良反应，均应作为药品不良反应或药品不良事件上报。 四、各临床科室药品不良反应监测员负责本科室药品不良反应信息收集，发生不良反应及时报告临床药学室并填写药品不良反应报告表，报送至临床药学室，并由临床药学室通过医院内网定期反馈给相关科室或全院，临床药学室通过国家药品不良反应监测信息网络报告，并填写纸质报表报县药品不良反应监测中心。 五、不良反应报告内容应当真实、完整、准确。 六、在医疗过程中，如发现药品不良反应病例，特别是严重、罕见或新的药品不良反应，医护人员应积极组织救治，最大限度保证病 人生命安全和身体健康，保存好相关药品留样，详细记录、分析，填写《药品不良反应/事件报告表》，同时向医务部门和药学部门报告。医师应将患者发生的药品不良反应如实记入病历中。 七、医务部门和药学部门应迅速组织有关专家对药物不良反应进行确认，根据不良反应的严重程度、后果及时处理，并按照有关规定进行上报。 八、若患者或家属对药品不良反应提出异议时，由临床医务人员和病人家属共同负责将药品封存后并保存于冰箱内，如患者及其家属对所用药品提出要检验，24小时内由医务部会同患者或家属前往市药品监督管理局备案。 九、获知或者发现药品群体不良事件后，应当立即通过电话或者传真等方式报所在地的县级药品监督管理部门、卫生行政部门和药品不良反应监测机构，必要时可以越级报告；同时填写《药品群体不良事件基本信息表》，对每一病例还应当及时填写《药品不良反应/事件报告表》，通过国家药品不良反应监测信息网络报告。 十、发现药品群体不良事件后应当积极救治患者，迅速开展临床调查，分析事件发生的原因，必要时可采取暂停药品的使用等紧急措施。 十一、药品不良反应报告和监测的工作人员应当对收集到的药品不良反应报告和监测资料进行分析和评价，并采取有效措施减少和防止药品不良反应的重复发生。 十二、加强药品不良反应监测和再评价工作，重点对化学药品注 关于发布《常见严重药品不良反应技术规范及评价标准》 的通知 各省级药品不良反应监测中心： 《常见严重药品不良反应技术规范及评价标准》业经2010年度全国药品不良反应监测中心主任工作会审议通过，现印发给你们，该标准可作为药品不良反应监测工作中的技术参考，请认真学习，努力提高药品不良反应监测工作的科学性、规范性。 特此通知 二0一0年二月二十日 过敏性休克药品不良反应判定评价标准 过敏性休克是外界某些抗原性物质进入机体后，主要通过免疫机制在短时间内发生的强烈全身变态反应综合征，由于抗体与抗原结合使机体释放一些生物活性物质如组胺、缓激肽、5-羟色胺和血小板激活因子等，导致全身毛细血管扩张和通透性增加，心排血量急剧下降，血压下降达休克水平。过敏性休克的表现与程度，依机体免疫反应强度、用药途径等的不同而存在很大差别。通常突然发生且很剧烈，若不及时处理，常可危及生命。 一、过敏性休克的临床特点 1、皮肤粘膜表现：往往是过敏性休克最早且最常出现的征兆，包括有一过性皮肤潮红、周围皮痒、口唇、舌部及四肢末梢麻木感，继之出现各种皮疹，重者可发生血管神经性水肿；还可出现鼻、眼、咽喉粘膜充血、水肿等。 2、呼吸系统表现：胸闷、气短、呼吸困难、窒息感、发绀等。 3、心血管系统表现常可见血压迅速下降，收缩压降至90mmHg以下或比基础血压降低20%或脉压差小于20mmHg。病人还出现心悸、出汗、面色苍白，然后发展为四肢厥冷、发绀、脉搏细弱、心动过速及晕厥等。 4、神经系统表现：头晕、乏力、眼花、神志淡漠或烦躁不安、大小便失禁、抽搐、昏迷等。 5、消化系统表现：恶心、呕吐、腹痛、腹胀、腹泻，严重的可出现血性腹泻。 目的：确保药品不良反应报告和监测工作的有效开展，有效控制药品风险，保障公众用药安全，建立药品不良反应组织机构及运行体系。 适用范围：适用于公司药品不良反应报告和监测工作。 责任人：药品不良反应办公室、质量保证部、后勤部、销售公司、科研中心 内容： 1.组织机构简图 2. 体系运行 2.1 信息采集途径 2.1.1 信息采集途径包括被动收集：销售人员、400热线投诉电话，和主动收集：上市前和上市后的临床研究、文献检索、国内外政府网站。 2.1.2 信息采集技巧：第一时间了解：判断事情的严重性。是否停药？是否上报？是否召回？ 第一时间控制：控制医生态度，控制患者情绪； 第一时间反馈：及时反馈至ADR管理员或药品不良反应办公室主任； 长期应对准备：掌握我公司产品主要不良反应及质量特性等，并具有一定的ADR判断能力，若不能独立解答患者疑问，切忌给予医疗服务建议，药品不良反应办公室给予支持。 信息收集要全：因其他原因不能全面收集ADR信息，至少收集以上四要素及时反馈至ADR管理员处，协助做好相关沟通工作。 2.2 单个病例管理 2.2.1 单个病例处理流程：收集（多渠道）→报告公司关联性评价→随访→上报ADR监测系统→纳入公司不良反应病例数据库。 2.2.2 出现药品不良反应及出现其他情况均应报告，即使没有伴随具体的不良事件，如： ·说明书已知一般不良反应、严重不良反应和新的不良反应 ·因药品停用而发生的事件 ·超适应症用药 ·孕妇暴露 ·药品无效 ·用药错误 ·死亡结局 ·出现未预期的治疗/临床益处 2.2.3 临床试验安全性信息报告 临床试验定义：任何在人体（病人或健康志愿者）进行的药物系统性研究，以证实或揭示试验药物的作用、不良反应或试验药物吸收、分布、代谢和排泄，其目的是确定试验药物的疗效与安全性。 临床试验类别：I、Ⅱ、Ⅲ、IV期临床试验、生物等效性试验、重点监测、一致性评价、临床有效性试验及其他安全与疗效对比研究等。 上报流程： 研究者上报所有不良事件；申办方上报严重不良事件（时限：死亡和危及生命为7天，其他情况15天），以电话、传真或EMS邮寄的形式向CFDA注册司、BFDA注册处及卫计委提交首次报告，及时提交随访报告，并将收集的所有不良事件报告1个工作日内反馈至公司不良反应办公室；不良反应办公室按法规时限要求上报上市后临床研究不良反应，上市前不良反应长期保存，待产品上市后纳入不良反应数据库并带入PSUR中。 2.2.4 个例不良反应/事件评价、上报 2.2.4.1 不良反应/事件类型： 依据《药品不良反应和监测管理办法》对一般的、新的和严重的不良反应的定义，对比说明书中不良反应描述，确定不良反应/事件的类型。 2.2.4.2 不良反应/事件关联性评价： 从时间相关性、药理作用/同类药物反应、去激发、再激发、剂量等方面对不良事件与药品之间关系进行评定。同时考虑的其他因素：原患疾病、相互作用、伴随药物、伴发疾病。时间相关性：用药前、用药过程中或延迟发生不良反应的可能。 2.2.4.3 药理作用/同类药物反应：不良事件发生时间是否与药理/毒理反应一致，同类药物的不良反应。 去激发：停药观察，去激发是否为阳性 再激发：去激发后再次给药观察，再激发是否为阳性。 给药剂量：规定给药剂量与实际给药剂量是否一致。 原患疾病：分析不良事件是否为原患疾病的症状，或治疗适应症的自然进程。 药物相互作用：协同作用、拮抗作用、配伍禁忌。 伴随药物/伴发疾病：是否导致不良事件的发生。 其他因素：是否存在其他风险因素，如吸烟史、饮酒史、过敏史、家族病史及不良反应病史等。 药品不良反应培训内容： 简介ADR（Adverse Drug Reaction）在按规定剂量正常应用药品的过程中产生的有害而非所期望的、与药品应用有因果关系的反应。在一种新药或药品的新用途的临床试验中，其治疗剂量尚未确定时，所有有害而非所期望的、与药品应用有因果关系的反应，也应视为药品不良反应。 根据《》第二十九条，本办法下列用语的含义是：药品不良反应是指合格药品在正常用法用量下出现的与用药目的无关的或意外的有害反应。 药品的不良反应 1、对人体有害的副作用。如阿托品被用于解除胃肠痉挛而引起口干等。 2、毒性反应。如引起失眠、耳鸣、贫血、肝功能损害等。 3、过敏反应。 4、其他不良反应。如、致畸、致突变、致癌等。 药品的不良反应分类 型不良反应 是由于药品的药理作用增强所致。特点是可以预测，与常规的药理作用有关，反应的发生与剂量有关，停药或减量后症状很快减轻或消失，发生率高（>1%），死亡率低。主要表现包括过度作用，医学教`育网搜集整理副作用、毒性反应、首剂效应、继发反应、停药综合症、后遗效应。 型不良反应 是与药品的正常药理作用完全无关的一种异常反应。特点是一般很难预测，常规毒理学筛选不能发现，发生率低（<1%=，死亡率高。进一步分类为遗传药理学不良反应和变态反应。 型不良反应 有些不良反应难以简单地归于A型或B型，有学者提出为C型不良反应。C型不良反应的特点是发生率高，用药史复杂或不全，非特异性（指药品），没有明确的时间关系，潜伏期较长。有些发生机制尚在探讨中。 构成的四个前提： 1、必须是合格药品。 2、必须在正常用法用量下出现。 3、必须与用药目的无关的或意外的反应。 4、必须是有害的反应。 表现及分类： 作用于机体，除了发挥治疗的功效外，有时还会由于种种原因而产生某些与 药品不良反应报告和监测检查资料清单 1.基本信息 1.1生产企业联系人联系方式（电话、电子邮箱、传真、通信地址、邮编等）。 1.2药品注册信息：生产企业药品注册情况列表，包括注册时间、上市时间、是否新药监测期品种、说明书变更、撤市、暂停、召回等情况等。 1.3 药品不良反应监测工作概况：描述药品不良反应监测工作如何有效开展，如工作流程、各部门之间协调管理（包括与全球或总部相关部门的协调）、人员安排等。 2.组织机构 2.1组织结构图：包括附属公司及机构情况，其中药品不良反应监测部门应该包括工作人员姓名和职务。 2.2 药品不良反应监测部门职责。 2.3 药品安全问题处理机制 3.人员管理 3.1 药品不良反应监测专职人员职责描述、专业背景、培训记录等。 3.2 药品不良反应报告相关部门人员培训记录。 4.质量管理体系 4.1管理制度：药品不良反应报告和监测、人员培训、资料管理等制度文件。 4.2程序文件须详细描述下述药品不良反应监测工作流程。 4.2.1个例药品不良反应报告处理。 4.2.2药品群体不良事件处理。 4.2.3境外发生的严重药品不良反应处理。 4.2.4定期安全性更新报告。 4.2.5药品重点监测。 4.2.6药品安全性信号检测。 4.2.7说明书更新程序。 4.2.8对于药品监管机构提出问题的回复程序。 4.2.9处理医学咨询和投诉程序。 4.2.10 文献检索程序。 4.2.11 评价与控制程序。 4.2.12数据处理程序：包括数据收集、整理，如有电子收集系统，应描述系统版本、系统的支持和维护等。 4.2.13资料存档：文件（包括电子文档）的归档和存储程序。 4.3质量管理体系审核：近一年内部审核和/或外部审核的总结报告、问题清单、整改情况等。 5.个例药品不良反应报告 个例药品不良反应报告汇总,包括年度药品不良反应报告总数、严重及死亡报告情况。医院药品不良反应监测小组机构及工作职责
药品不良反应报告表填写示例及填写说明
常见药物不良反应
常见药物不良反应
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药品不良反应
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严重药品不良反应判定标准
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药品不良反应培训内容
药品不良反应报告和监测检查资料清单