Azathioprine
Only valid for adult patients. Azathioprine must be at a dose of at least 1 mg per kg per day.
| Adverse event | Brief description of minimum grade | National Institutes of Health common toxicity criteria grade |
|---|---|---|
| Blood or bone marrow | ||
| Anaemia | Haemoglobin <80 g per L | 3 (or higher) |
| Leukopenia | Total white cell count <3 x 109 per L | 2 (or higher) |
| Thrombocytopenia | Platelets <50 x 109 per L | 3 (or higher) |
| Neutropenia | Total neutrophils <1.0 x 109 per L | 3 (or higher) |
| Dermatology or skin | ||
| Alopecia | Pronounced hair loss | 2 (or higher) |
| Rash or desquamation | Scattered macular or papular eruption or erythema with pruritis or other associated symptoms covering <50% of body surface or localised desquamation or other lesions covering <50% of body surface | 2 (or higher) |
| Gastrointestinal | ||
| Diarrhoea | Increase of 4-6 stools per day over pre-treatment | 2 (or higher) |
| Nausea | Oral intake significantly decreased | 2 (or higher) |
| Pancreatitis | Abdominal pain with pancreatic enzyme elevation | 3 (or higher) |
| Stomatitis | Painful erythema, oedema or ulcers but able to eat or swallow | 2 (or higher) |
| Vomiting | 2 or more episodes per 24 hours over pre-treatment | 2 (or higher) |
| Hepatic | ||
| Bilirubin | >1.5 x upper limit of normal | 2 (or higher) |
| Transaminases | Alanine aminotransferase or aspartate aminotransferase >2.5 x upper limit of normal oralanine aminotransferase or aspartate aminotransferase >1.5 x upper limit of normal on 3 occasions over a 3-month period | 2 (or higher) |
| Serum alkaline phosphatase | 2.5 x upper limit of normal | 2 (or higher) |
| Neurology or senses | ||
| Headaches (severe) | Severe pain, pain or analgesics severely interfere with activities of daily living | 3 (or higher) |
| Pulmonary | ||
| Pneumonitis or pulmonary infiltrates | Radiographic changes, respiratory function test abnormalities and requiring steroids or diuretics | 2 (or higher) |
| Other | ||
| Allergic reaction | Urticaria, drug fever >38°C or bronchospasm | 2 (or higher) |
| Fatigue, malaise | Severe, loss of ability to perform some activities | 3 (or higher) |
| Fever (in the absence of neutropenia) | Body temp >39°C (oral or tympanic) | 2 (or higher) |
| Infection | Severe or systemic infection, requiring intravenous antimicrobial treatment or hospitalisation | 3 (or higher) |
| Secondary malignancy | Secondary malignancy present | 4 |
Cyclosporin
Only valid for adult patients. Cyclosporin must be at a dose of at least 2 mg per kg per day.
| Adverse event | Brief description of minimum grade | National Institutes of Health common toxicity criteria grade |
|---|---|---|
| Blood or bone marrow | ||
| Anaemia | Haemoglobin <80 g per L | 3 (or higher) |
| Leukopenia | Total white cell count <3 x 109 per L | 2 (or higher) |
| Thrombocytopenia | Platelets <50 x 109 per L | 3 (or higher) |
| Neutropenia | Total neutrophils <1.0 x 109 per L | 3 (or higher) |
| Cardiovascular | ||
| Hypertension | Recurrent or persistent rise of >20 mmHg diastolic blood pressure or rise to >150/90 on 2 occasions if blood pressure previously normal | 2 (or higher) |
| Fluid retention | Symptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation | 3 (or higher) |
| Dermatology or skin | ||
| Rash or desquamation | Scattered macular or papular eruption or erythema with pruritis or other associated symptoms covering <50% of body surface or localised desquamation or other lesions covering <50% of body surface | 2 (or higher) |
| Gastrointestinal | ||
| Diarrhoea | Increase of 4-6 stools per day over pre-treatment | 2 (or higher) |
| Nausea | Oral intake significantly decreased | 2 (or higher) |
| Pancreatitis | Abdominal pain with pancreatic enzyme elevation | 3 (or higher) |
| Vomiting | 2 or more episodes per 24 hours over pre-treatment | 2 (or higher) |
| Weight gain or loss | 20% or more weight gain or loss | 3 (or higher) |
| Hepatic | ||
| Bilirubin | >1.5 x upper limit of normal | 2 (or higher) |
| Transaminases | Alanine aminotransferase or aspartate aminotransferase >2.5 x upper limit of normal or alanine aminotransferase or aspartate aminotransferase >1.5 x upper limit of normal on 3 occasions over a 3-month period | 2 (or higher) |
| Serum alkaline phosphatase | 2.5 x upper limit of normal | 2 (or higher) |
| Musculoskeletal | ||
| Muscle weakness | Symptomatic and interfering with function | 2 (or higher) |
| Neurology or senses | ||
| Ataxia (incoordination) | Mild symptoms interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Decreased level of consciousness | Somnolence or sedation interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Headaches (severe) | Severe pain, pain or analgesics severely interfere with activities of daily living | 3 (or higher) |
| Hearing | Tinnitus or hearing loss not requiring hearing aid or treatment | 2 (or higher) |
| Mood alteration | Moderate mood alteration interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Neuropathy - sensory | Objective sensory loss or paraesthesia interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Seizure(s) | Seizures in which consciousness is altered | 3 (or higher) |
| Vision | Symptomatic and interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Renal | ||
| Haematuria | Macroscopic (or dipstick +++) confirmed on 2 separate occasions | 2 (or higher) |
| Proteinuria | >1.0 g per 24 hours, elevated urine protein-creatinine ratios, dipstick protein ++ or greater, confirmed on 2 separate occasions | 2 (or higher) |
| Renal impairment | Creatinine >1.5 × upper limit of normal or creatinine clearance <30 mL per min | 2 (or higher) |
| Other | ||
| Allergic reaction | Urticaria, drug fever >38°C or bronchospasm | 2 (or higher) |
| Fatigue, malaise | Severe, loss of ability to perform some activities | 3 (or higher) |
| Fever (in the absence of neutropenia) | Body temp >39°C (oral or tympanic) | 2 (or higher) |
| Hyperkalaemia | Potassium >6 mmol per L | 3 (or higher) |
| Infection | Severe or systemic infection, requiring intravenous antimicrobial treatment or hospitalisation | 3 (or higher) |
| Secondary malignancy | Secondary malignancy present | 4 |
Hydroxychloroquine
Only valid for adult patients. Hydroxychloroquine must be at a dose of at least 200 mg daily
| Adverse event | Brief description of minimum grade | National Institutes of Health common toxicity criteria grade |
|---|---|---|
| Blood or bone marrow | ||
| Anaemia | Haemoglobin <80 g per L | 3 (or higher) |
| Leukopenia | Total white cell count <3 x 109 per L | 2 (or higher) |
| Thrombocytopenia | Platelets <50 x 109 per L | 3 (or higher) |
| Neutropenia | Total neutrophils <1.0 x 109 per L | 3 (or higher) |
| Dermatology or skin | ||
| Alopecia | Pronounced hair loss | 2 (or higher) |
| Rash or desquamation | Scattered macular or papular eruption or erythema with pruritis or other associated symptoms covering <50% of body surface or localised desquamation or other lesions covering <50% of body surface | 2 (or higher) |
| Gastrointestinal | ||
| Diarrhoea | Increase of 4-6 stools per day over pre-treatment | 2 (or higher) |
| Nausea | Oral intake significantly decreased | 2 (or higher) |
| Stomatitis | Painful erythema, oedema or ulcers but able to eat or swallow | 2 (or higher) |
| Vomiting | 2 or more episodes per 24 hours over pre-treatment | 2 (or higher) |
| Hepatic | ||
| Bilirubin | >1.5 x upper limit of normal | 2 (or higher) |
| Transaminases | Alanine aminotransferase or aspartate aminotransferase >2.5 x upper limit of normal or alanine aminotransferase or aspartate aminotransferase >1.5 x upper limit of normal on 3 occasions over a 3-month period | 2 (or higher) |
| Serum alkaline phosphatase | 2.5 x upper limit of normal | 2 (or higher) |
| Musculoskeletal | ||
| Muscle weakness | Symptomatic and interfering with function | 2 (or higher) |
| Neurology or senses | ||
| Headaches (severe) | Severe pain, pain or analgesics severely interfere with activities of daily living | 3 (or higher) |
| Hearing | Tinnitus or hearing loss not requiring hearing aid or treatment | 2 (or higher) |
| Neuropathy - motor | Objective weakness interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Seizure(s) | Seizures in which consciousness is altered | 3 (or higher) |
| Vision | Symptomatic and interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Vision - cornea or retina | Symptomatic corneal or retinal changes present | 1 (or higher) |
| Other | ||
| Allergic reaction | Urticaria, drug fever >38°C or bronchospasm | 2 (or higher) |
Leflunomide
Only valid for adult patients. Leflunomide must be at a dose of at least 10 mg daily.
| Adverse event | Brief description of minimum grade | National Institutes of Health common toxicity criteria grade |
|---|---|---|
| Blood or bone marrow | ||
| Anaemia | Haemoglobin <80 g per L | 3 (or higher) |
| Leukopenia | Total white cell count <3 x 109 per L | 2 (or higher) |
| Thrombocytopenia | Platelets <50 x 109 per L | 3 (or higher) |
| Neutropenia | Total neutrophils <1.0 x 109 per L | 3 (or higher) |
| Cardiovascular | ||
| Arrhythmia | Symptomatic and requiring therapy | 3 (or higher) |
| Hypertension | Recurrent or persistent rise of >20 mmHg diastolic blood pressure or rise to >150/90 on 2 occasions if blood pressure previously normal | 2 (or higher) |
| Fluid retention | Symptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation | 3 (or higher) |
| Dermatology or skin | ||
| Alopecia | Pronounced hair loss | 2 (or higher) |
| Rash or desquamation | Scattered macular or papular eruption or erythema with pruritis or other associated symptoms covering 50% of body surface or localised desquamation or other lesions covering 50% of body surface | 2 (or higher) |
| Gastrointestinal | ||
| Diarrhoea | Increase of 4-6 stools per day over pre-treatment | 2 (or higher) |
| Nausea | Oral intake significantly decreased | 2 (or higher) |
| Stomatitis | Painful erythema, oedema or ulcers but able to eat or swallow | 2 (or higher) |
| Weight gain or loss | 20% or more weight gain or loss | 3 (or higher) |
| Hepatic | ||
| Bilirubin | >1.5 x upper limit of normal | 2 (or higher) |
| Transaminases | Alanine aminotransferase or aspartate aminotransferase 2.5 x upper limit of normal or alanine aminotransferase or aspartate aminotransferase >1.5 x upper limit of normal on 3 occasions over a 3-month period | 2 (or higher) |
| Serum alkaline phosphatase | 2.5 x upper limit of normal | 2 (or higher) |
| Neurology or senses | ||
| Headaches (severe) | Severe pain, pain or analgesics severely interfere with activities of daily living | 3 (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 | 2 (or higher) |
| Pulmonary | ||
| Cough (severe) | Severe cough or coughing spasm, poor control or unresponsive to treatment. Evidence of reversal on cessation of treatment. | 3 (or higher) |
| Pneumonitis or pulmonary infiltrates | Radiographic changes, respiratory function test abnormalities and requiring steroids or diuretics | 2 (or higher) |
| Pulmonary fibrosis | Respiratory function test abnormalities and requiring steroids or diuretics | 2 (or higher) |
| Pulmonary symptoms - new or worsening (probable drug-induced pneumonitis) | Development of syndrome consistent with drug-induced pneumonitis (such as cough, dyspnoea, fever, hypoxaemia) with lung infiltrates on imaging (refer to Searles McKendry criteria) | Not applicable |
| Renal | ||
| Haematuria | Macroscopic (or dipstick +++) confirmed on 2 separate occasions | 2 (or higher) |
| Proteinuria | >1.0 g per 24 hours, elevated urine protein-creatinine ratios, dipstick protein ++ or greater, confirmed on 2 separate occasions | 2 (or higher) |
| Renal impairment | Creatinine >1.5 × upper limit of normal or creatinine clearance <30 mL per min | 2 (or higher) |
| Other | ||
| Allergic reaction | Urticaria, drug fever >38°C or bronchospasm | 2 (or higher) |
| Fatigue, malaise | Severe, loss of ability to perform some activities | 3 (or higher) |
| Fever (in the absence of neutropenia) | Body temp >39°C (oral or tympanic) | 2 (or higher) |
| Hypokalaemia | Potassium <3 mmol per L | 3 (or higher) |
| Infection | Severe or systemic infection, requiring intravenous antimicrobial treatment or hospitalisation | 3 (or higher) |
| Secondary malignancy | Secondary malignancy present | 4 |
Methotrexate
Paediatric patients
Toxicity due to methotrexate is defined as evidence of hepatotoxicity with repeated elevations of transaminases, bone marrow suppression temporally related to methotrexate use, pneumonitis, or serious sepsis.
Adult patients
Methotrexate must be at a dose of at least 20 mg weekly.
| Adverse event | Brief description of minimum grade | National Institutes of Health common toxicity criteria grade |
|---|---|---|
| Blood or bone marrow | ||
| Anaemia | Haemoglobin <80 g per L | 3 (or higher) |
| Leukopenia | Total white cell count <3 x 109 per L | 2 (or higher) |
| Thrombocytopenia | Platelets <50 x 109 per L | 3 (or higher) |
| Neutropenia | Total neutrophils <1.0 x 109 per L | 3 (or higher) |
| Cardiovascular | ||
| Pericardial effusion or pericarditis | Pericarditis (pericardial rub, electrocardiogram changes or chest pain) | 2 (or higher) |
| Thrombosis or embolism | Requiring anticoagulant therapy | 3 (or higher) |
| Dermatology or skin | ||
| Alopecia | Pronounced hair loss | 2 (or higher) |
| Rash or desquamation | Scattered macular or papular eruption or erythema with pruritis or other associated symptoms covering <50% of body surface or localised desquamation or other lesions covering <50% of body surface | 2 (or higher) |
| Gastrointestinal | ||
| Diarrhoea | Increase of 4-6 stools per day over pre-treatment | 2 (or higher) |
| Nausea | Oral intake significantly decreased, and symptoms do not improve with at least 2 of the following measures:
A minimum of 3 doses of methotrexate should have been trialled |
2 (or higher) |
| Pancreatitis | Abdominal pain with pancreatic enzyme elevation | 3 (or higher) |
| Stomatitis | Painful erythema, oedema or ulcers but able to eat or swallow | 2 (or higher) |
| Vomiting | 2 or more episodes per 24 hours over pre-treatment | 2 (or higher) |
| Hepatic | ||
| Bilirubin | >1.5 x upper limit of normal | 2 (or higher) |
| Transaminases | Alanine aminotransferase or aspartate aminotransferase >2.5 x upper limit of normal or alanine aminotransferase or aspartate aminotransferase >1.5 x upper limit of normal on 3 occasions over a 3-month period | 2 (or higher) |
| Serum alkaline phosphatase | 2.5 x upper limit of normal | 2 (or higher) |
| Musculoskeletal | ||
| Osteonecrosis (avascular necrosis) |
Symptomatic and interfering with function | 2 (or higher) |
| Osteoporosis | Symptomatic and requiring treatment | 3 (or higher) |
| Neurology or senses | ||
| Decreased level of consciousness | Somnolence or sedation interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Headaches (severe) | Severe pain, pain or analgesics severely interfere with activities of daily living | 3 (or higher) |
| Hearing | Tinnitus or hearing loss not requiring hearing aid or treatment | 2 (or higher) |
| Mood alteration | Moderate mood alteration interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Seizure(s) | Seizures in which consciousness is altered | 3 (or higher) |
| Vision | Symptomatic and interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Pulmonary | ||
| Cough (severe) | Severe cough or coughing spasm, poor control or unresponsive to treatment. Evidence of reversal on cessation of treatment | 3 (or higher) |
| Pneumonitis or pulmonary infiltrates | Radiographic changes, respiratory function test abnormalities and requiring steroids or diuretics | 2 (or higher) |
| Pulmonary fibrosis | Respiratory function test abnormalities and requiring steroids or diuretics | 2 (or higher) |
| Pulmonary symptoms - new or worsening (probable drug-induced pneumonitis) | Development of syndrome consistent with drug-induced pneumonitis (such as cough, dyspnoea, fever, hypoxaemia) with lung infiltrates on imaging (refer to Searles McKendry criteria) | Not applicable |
| Renal | ||
| Haematuria | Macroscopic (or dipstick +++) confirmed on 2 separate occasions | 2 (or higher) |
| Renal impairment | Creatinine >1.5 × upper limit of normal or creatinine clearance <30 mL per min | 2 (or higher) |
| Other | ||
| Allergic reaction | Urticaria, drug fever >38°C or bronchospasm | 2 (or higher) |
| Fatigue, malaise | Severe, loss of ability to perform some activities | 3 (or higher) |
| Fever (in the absence of neutropenia) | Body temp >39°C (oral or tympanic) | 2 (or higher) |
| Infection | Severe or systemic infection, requiring intravenous antimicrobial treatment or hospitalisation | 3 (or higher) |
| Nodulosis (following introduction of methotrexate therapy) | Development of multiple new nodules causing significant local pressure symptoms and distress to patient | |
| Secondary malignancy | Secondary malignancy present | 4 |
Sulfasalazine
Only valid for adult patients. Sulfasalazine must be at a dose of at least 2 g daily.
| Adverse event | Brief description of minimum grade | National Institutes of Health common toxicity criteria grade |
|---|---|---|
| Blood or bone marrow | ||
| Anaemia | Haemoglobin <80 g per L | 3 (or higher) |
| Leukopenia | Total white cell count <3 x 109 per L | 2 (or higher) |
| Thrombocytopenia | Platelets <50 x 109 per L | 3 (or higher) |
| Neutropenia | Total neutrophils <1.0 x 109 per L | 3 (or higher) |
| Dermatology or skin | ||
| Alopecia | Pronounced hair loss | 2 (or higher) |
| Rash or desquamation | Scattered macular or papular eruption or erythema with pruritis or other associated symptoms covering <50% of body surface or localised desquamation or other lesions covering <50% of body surface | 2 (or higher) |
| Gastrointestinal | ||
| Diarrhoea | Increase of 4-6 stools per day over pre-treatment | 2 (or higher) |
| Nausea | Oral intake significantly decreased | 2 (or higher) |
| Pancreatitis | Abdominal pain with pancreatic enzyme elevation | 3 (or higher) |
| Stomatitis | Painful erythema, oedema or ulcers but able to eat or swallow | 2 (or higher) |
| Vomiting | 2 or more episodes per 24 hours over pre-treatment | 2 (or higher) |
| Hepatic | ||
| Bilirubin | >1.5 x upper limit of normal | 2 (or higher) |
| Transaminases | Alanine aminotransferase or aspartate aminotransferase >2.5 x upper limit of normal or alanine aminotransferase or aspartate aminotransferase >1.5 x upper limit of normal on 3 occasions over a 3-month period | 2 (or higher) |
| Serum alkaline phosphatase | 2.5 x upper limit of normal | 2 (or higher) |
| Neurology or senses | ||
| Headaches (severe) | Severe pain, pain or analgesics severely interfere with activities of daily living | 3 (or higher) |
| Hearing | Tinnitus or hearing loss not requiring hearing aid or treatment | 2 (or higher) |
| Mood alteration | Moderate mood alteration interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Neuropathy - sensory | Objective sensory loss or paraesthesia interfering with function but not interfering with activities of daily living | 2 (or higher) |
| Seizure(s) | Seizures in which consciousness is altered | 3 (or higher) |
| Pulmonary | ||
| Cough (severe) | Severe cough or coughing spasm, poor control or unresponsive to treatment. Evidence of reversal on cessation of treatment | 3 (or higher) |
| Pneumonitis or pulmonary infiltrates | Radiographic changes, respiratory function test abnormalities and requiring steroids or diuretics | 2 (or higher) |
| Pulmonary fibrosis | Respiratory function test abnormalities and requiring steroids or diuretics | 2 (or higher) |
| Renal | ||
| Haematuria | Macroscopic (or dipstick +++) confirmed on 2 separate occasions | 2 (or higher) |
| Proteinuria | >1.0 g per 24 hours, elevated urine protein-creatinine ratios, dipstick protein ++ or greater, confirmed on 2 separate occasions | 2 (or higher) |
| Renal impairment | Creatinine >1.5 × upper limit of normal or creatinine clearance <30 mL per min | 2 (or higher) |
| Other | ||
| Allergic reaction | Urticaria, drug fever >38°C or bronchospasm | 2 (or higher) |
| Fever (in the absence of neutropenia) | Body temp >39°C (oral or tympanic) | 2 (or higher) |