Use the following toxicity and severity descriptors in conjunction with the authority application when demonstrating patient’s intolerance to DMARDs treatment:
- ALT - alanine aminotransferase
- AST - aspartate aminotransferase
- BP - blood pressure
- ECG - electrocardiogram
- IV - intravenous
- LV - left ventricle
- NIH - National Institutes of Health
- PT - Prothrombin time
- ULN - upper limit of normal
- WCC - white cell count.
| Adverse event | Brief description of minimum grade | NIH common toxicity criteria grade |
|---|---|---|
| Blood or bone marrow | ||
| Anaemia | Haemoglobin < 80 g per L | 3 (or higher) |
| Leukopenia | Total WCC < 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) |
| Cardiac LV function | Congestive cardiac failure responsive to treatment | 3 (or higher) |
| Fluid retention | Symptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation | 3 (or higher) |
| Hypertension | Recurrent or persistent rise of > 20 mmHg diastolic BP or rise to > 150 over 90 on 2 occasions if BP previously normal | 2 (or higher) |
| Pericardial effusion or pericarditis | Pericarditis (pericardial rub, ECG changes or chest pain) | 2 (or higher) |
| Thrombosis or embolism | Requiring anticoagulant therapy | 3 (or higher) |
| Coagulation | ||
| Prothrombin time | PT > 2 x ULN | 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 | 2 (or higher) |
| Gastrointestinal | ||
| Diarrhoea | Increase of 4-6 stools per day over pre-treatment | 2 (or higher) |
| Nausea | Oral intake significantly decreased, and where the causative DMARD is methotrexate, symptoms that don't respond to at least 2 of the following:
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) |
| Weight gain or loss | 20% or more weight gain or loss | 3 (or higher) |
| Hepatic | ||
| Bilirubin | > 1.5 x ULN | 2 (or higher) |
| Transaminases | ALT or AST > 2.5 x ULN, or ALT or AST > 1.5 x ULN on 3 occasions over a 3-month period | 2 (or higher) |
| Ç Serum alkaline phosphatase | 2.5 x ULN | 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) |
| 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 (for example, cough, dyspnoea, fever, hypoxaemia) with lung infiltrates on imaging (refer Searles McKendry criteria) | |
| 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 ULN 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, systemic infection, requiring IV 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 |