Crohn disease toxicity criteria and severity descriptors

Toxicity criteria and severity descriptors for the listing of biological agents for Crohn disease on the Pharmaceutical Benefits Scheme (PBS).

Prednisolone

Adverse event Brief description of minimum grade National Institutes of Health common toxicity criteria grade
Gastrointestinal
Gastric irritation or ulcer Requiring medical management 2 (or higher)
Nausea Oral intake significantly reduced 2 (or higher)
Vomiting 2 or more episodes in 24 hours over pre-treatment 2 (or higher)
Weight gain ≥ 20% weight gain 3 (or higher)
Cardiovascular
Hypertension Requiring therapy or more intensive therapy than previously 3 (or higher)
Fluid retention Symptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation 3 (or higher)
Central nervous system
past psychiatric history is not a contraindication
Insomnia Frequent insomnia interfering with activities of daily living 3 (or higher)
Mood alteration Severe mood alteration interfering with activities of daily living 3 (or higher)
Personality or behaviour Disruptive to patient or family, requiring mental health intervention 3 (or higher)
Restlessness Severe 3 (or higher)
Dermatological
Acne or dermatological conditions Severe 3 (or higher)
Purpura or bruising Generalised or mucosal petechiae 3 (or higher)
Impaired healing Requiring medical management 2 (or higher)
Laboratory
Hyperglycaemia Glucose 13.9 mmol per L or higher 3 (or higher)
Hypertriglyceridaemia > 5-10 x upper limit of normal 3 (or higher)
Hypokalaemia < 3.0 mmol per L 3 (or higher)
Endocrine
Cushingoid appearance Present 3 (or higher)
Disordered menstruation Very irregular over pre-treatment 2 (or higher)
Ocular
Cataracts Symptomatic visual loss requiring treatment or interfering with function 3 (or higher)
Glaucoma Increase in intraocular pressure with retinal changes 2 (or higher)
Musculoskeletal
Osteoporosis or fracture Symptomatic, interfering with activities of daily living  
Avascular necrosis Symptomatic, interfering with function 2 (or higher)
Myopathy Symptomatic, interfering with function 2 (or higher)
Miscellaneous
Immunosuppression Severe, requiring treatment withdrawal  
Impaired healing Symptomatic, interfering with activities of daily living  
Growth retardation    

Azathioprine

Adverse event Brief description of minimum grade National Institutes of Health common toxicity criteria grade
Neoplasms
New malignancy Serious malignancy present 4
Gastrointestinal
Nausea Oral intake significantly reduced 2 (or higher)
Vomiting 2 or more episodes in 24 hours over pre-treatment 2 (or higher)
Diarrhoea Increase of more than 4 stools per day over pre-treatment, or incontinence 2 (or higher)
Stomatitis Painful erythema, oedema or ulcers but can eat or swallow 2 (or higher)
Abdominal pain Severe pain, analgesia interfering with activities of daily living 3 (or higher)
Pancreatitis Abdominal pain with pancreatic enzyme elevation 3 (or higher)
Hepatic
Bilirubin > 1.5 x upper limit of normal 2 (or higher)
Hepatic enzymes > 2.5 x upper limit of normal 2(or higher)
Dermatological
Rash Rash with associated symptoms over less than 50% of body surface 2 (or higher)
Alopecia Pronounced hair loss 3 (or higher)
Pulmonary
Pneumonitis X-ray changes, requiring steroids and diuretics 2 (or higher)
Miscellaneous
Hypersensitivity Rash, drug fever >38 °C, aches, etc. 2 (or higher)
Immunosuppression or atypical infection Severe or systemic infection requiring intravenous antimicrobial treatment or hospitalisation 3 (or higher)
Haematological
Leukocytes < 2 x 109 per L 3 (or higher)
Haemoglobin < 80 g per L 3 (or higher)
Thrombocytes < 50 x 109 per L 3 (or higher)

Mercaptopurine

Adverse event Brief description of minimum grade National Institutes of Health common toxicity criteria grade
Haematological
Leukocytes < 2 x 109 per L 3 (or higher)
Haemoglobin < 80 g per L 3 (or higher)
Thrombocytes < 50 x 109 per L 3 (or higher)
Neoplasms    
New malignancy Serious malignancy present 4
Gastrointestinal
Nausea Oral intake significantly reduced 2 (or higher)
Vomiting 2 or more episodes in 24 hours over pre-treatment 2 (or higher)
Diarrhoea Increase of more than 4 stools per day over pre-treatment, or incontinence 2 (or higher)
Stomatitis Painful erythema, oedema or ulcers but can eat or swallow 2 (or higher)
Abdominal pain Severe pain, analgesia interfering with activities of daily living 3 (or higher)
Pancreatitis Abdominal pain with pancreatic enzyme elevation 3 (or higher)
Hepatic
Bilirubin > 1.5 x upper limit of normal 2 (or higher)
Hepatic enzymes > 2.5 x upper limit of normal 2 (or higher)
Dermatological
Rash Rash with associated symptoms over less than 50% of body surface 2 (or higher)
Alopecia Pronounced hair loss 3 (or higher)
Pulmonary
Pneumonitis X-ray changes, requiring steroids and diuretics 2 (or higher)
Miscellaneous
Hypersensitivity Rash, drug fever >38 °C, aches, etc. 2 (or higher)
Immunosuppression or atypical infection Severe or systemic infection requiring intravenous antimicrobial treatment or hospitalisation 3 (or higher)

Methotrexate

Adverse event Brief description of minimum grade National Institutes of Health common toxicity criteria grade
Alimentary tract
Diarrhoea Increase of more than 4 stools per day over pre-treatment, or incontinence 2 (or higher)
Nausea Oral intake significantly decreased and symptoms that do not respond to at least 2 of the following:
  • reduction of the methotrexate dose
  • folinic acid or folic acid supplementation
  • switching from oral dosing to intramuscular dosing
  • splitting the methotrexate dose over 12 hours

A minimum of 3 doses of methotrexate should have been trialled

2 (or higher)
Stomatitis Painful erythema, oedema or ulcers but able to eat or swallow 2 (or higher)
Vomiting 2 or more episodes in 24 hours over pre-treatment 2 (or higher)
Blood
Haemoglobin < 80 g per L 3 (or higher)
Clinical haemorrhage Requiring transfusion 3 (or higher)
Leukocytes < 2 x 109 per L 3 (or higher)
Phlebitis Present 2 (or higher)
Thrombocytes < 50 x109 per L 3 (or higher)
Central nervous system
Ataxia Mild symptoms interfering with function but not interfering with activities of daily living 2 (or higher)
Hearing Tinnitus or hearing loss not requiring treatment 2 (or higher)
Incoordination Mild symptoms interfering with function but not interfering with activities of daily living 2 (or higher)
Mood alteration Moderate mood alteration interfering with function but not interfering with activities of daily living 2 (or higher)
Vision Symptomatic and interfering with function but not interfering with activities of daily living 3 (or higher)
Dermatological
Alopecia Pronounced hair loss 2 (or higher)
Rash Rash with associated symptoms over less than 50% of body surface 2 (or higher)
Hepatic
Bilirubin > 1.5 x upper limit of normal 2 (or higher)
Elevated transaminases
  • Alanine aminotransferase and/or aspartate aminotransferase > 2.5 x upper limit of normal
    or
  • Alanine aminotransferase and/or aspartate aminotransferase > 1.5 x upper limit of normal on 3 occasions over a 3 month period
2 (or higher)
Elevated serum alkaline phosphatase 2.5 x upper limit of normal 2 (or higher)
Respiratory  
Pneumonitis/pulmonary infiltrates Radiographic changes requiring steroids/diuretics 2 (or higher)
Pulmonary fibrosis Requiring steroids/diuretics 2 (or higher)
Cough (severe) Severe cough/coughing spasm that is poorly controlled or unresponsive to treatment. Evidence of reversal on treatment withdrawal 3 (or higher)
Renal
Renal impairment Creatinine clearance <30 ml/min 3 (or higher)
Other
Allergic reaction Urticaria, drug >38 0C or broncospasm 2 (or higher)
Infection Severe, systemic infection, requiring IV antimicrobial treatment or hospitalisation 3 (or higher)
Headaches (severe) Severe pain (requiring compound analgesics) where pain/analgesics severely interfere with activities of daily living 3 (or higher)
Nodulosis (following introduction of methotrexate therapy) Development of multiple new nodules causing significant local pressure symptoms and distress to the patient  

Page last updated: 15 November 2016

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