Toxicity and severity descriptors

Toxicity and severity descriptors for the listing of biological agents on the PBS for adults.

Acitretin

At least 0.4mg/kg/day

Adverse event Brief description of minimum grade of toxicity National Institutes of Health
common toxicity criteria grade
Bilirubin > 1.5 x ULN 2 (or higher)
Transaminases ALT and/or AST > 2.5 x ULN or ALT and/or AST > 1.5 x ULN on three occasions over a three month period 2 (or higher)
Serum alkaline phosphatase 2.5 x ULN 2 (or higher)
Use contraindicated in those with pre-existing significant renal disease Creatinine > 1.5 ULN 2 (or higher)
Retinoic acid syndrome Symptoms of a degree to indicate steroid use 2 (or higher)
Pseudotumour cerebri Headache, nausea and vomiting associated with raised intracranial pressure  
Nausea Oral intake significantly decreased 2 (or higher)
Skin peeling Development of fissures on the palms and soles which cause sufficient discomfort and pain to prevent normal day-to-day duties, and which have not responded to regular and liberal applications of a moisturising agent  
Skin burning Sufficient to disturb activities of daily living and to disturb the normal sleep pattern  

Cyclosporin

At least 2mg/kg/day

Adverse event Brief description of minimum grade of toxicity National Institutes of Health
common toxicity criteria grade
Blood/bone marrow
Anaemia Haemoglobin < 80 g/L 3 (or higher)
Leukopenia Total WCC < 3 x 109/L 2 (or higher)
Thrombocytopenia Platelets < 50 x 109/L 3 (or higher)
Neutropenia Total neutrophils < 1.0 x 109/L 3 (or higher)
Cardiovascular
Hypertension Recurrent/persistent rise of > 20 mmHg diastolic BP or rise to > 150/90 on two occasions if BP previously normal 2 (or higher)
Fluid retention Symptomatic, limiting function, unresponsive to therapy or requiring drug discontinuation 3 (or higher)
Dermatology/skin
Rash/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/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/24 hours over pre-treatment 2 (or higher)
Weight gain/loss 20% or more weight gain or loss 3 (or higher)
Hepatic
Bilirubin > 1.5 x ULN 2 (or higher)
Transaminases ALT and/or AST > 2.5 x ULN or ALT and/or AST > 1.5 x ULN on three occasions over a three month period 2 (or higher)
g Serum alkaline phosphatase 2.5 x ULN 2 (or higher)
Musculoskeletal
Muscle weakness Symptomatic and interfering with function 2 (or higher)
Neurology/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 that 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 two separate occasions 2 (or higher)
Proteinuria > 1.0g/24 hours, elevated urine protein/creatinine ratios, (dipstick protein ++ or greater), confirmed on two separate occasions 2 (or higher)
Renal impairment Creatinine > 1.5 ULN or creatinine clearance < 30mL/min 2 (or higher)
Other
Allergic reaction Urticaria, drug fever > 38°C and/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/L 3 (or higher)
Infection Severe, systemic infection, requiring IV antimicrobial treatment or hospitalisation 3 (or higher)
Secondary malignancy Secondary malignancy present 4

Methotrexate

At least 10mg weekly

Adverse event Brief description of minimum grade of toxicity National Institutes of Health
common toxicity criteria grade
Blood/bone marrow
Anaemia Haemoglobin < 80 g/L 3 (or higher)
Leukopenia Total WCC < 3 x 109/L 2 (or higher)
Thrombocytopenia Platelets < 50 x 109/L 3 (or higher)
Neutropenia Total neutrophils < 1.0 x 109/L 3 (or higher)
Cardiovascular
Pericardial effusion/pericarditis Pericarditis (pericardial rub, ECG changes or chest pain) 2 (or higher)
Thrombosis/embolism Requiring anticoagulant therapy 3 (or higher)
Dermatology/skin
Alopecia Pronounced hair loss 2 (or higher)
Rash/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/day over pre-treatment 2 (or higher)
Nausea Oral intake significantly decreased, and symptoms do not improve with at least two of the following measures:
  1. reduction of the methotrexate dose
  2. folinic acid/folic acid supplementation
  3. switching from oral to intramuscular dosing
  4. dividing the methotrexate dose over 12 hours.

A minimum of three 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/24 hours over pre-treatment 2 (or higher)
Hepatic
Bilirubin > 1.5 x ULN 2 (or higher)
Transaminases ALT and/or AST > 2.5 x ULN or ALT and/or AST > 1.5 x ULN on three occasions over a three month period 2 (or higher)
g Serum alkaline phosphatase 2.5 x ULN 2 (or higher)
Musculoskeletal
Osteonecrosis Symptomatic and interfering with function 2 (or higher) (avascular necrosis)
Osteoporosis Symptomatic and requiring treatment 3 (or higher)
Neurology/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 that 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/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 (e.g. cough, dyspnoea, fever,  
Renal
Haematuria Macroscopic (or dipstick +++) confirmed on two separate occasions 2 (or higher)
Renal impairment Creatinine > 1.5 ULN or creatinine clearance < 30mL/min 2 (or higher)
Other
Allergic reaction Urticaria, drug fever > 38°C and/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)
Secondary malignancy Secondary malignancy present 4

Phototherapy toxicity

Required minimum dose of three treatments per week

Adverse event Brief description of minimum grade of toxicity National Institutes of Health
common toxicity criteria grade
Severe photosensitivity reaction Erythema with desquamation 3 (or higher)
Pruritis Intense or widespread and interfering with activities of daily living (ADLs) 3 (or higher)
Development of melanoma    
Development of non melanoma skin cancer    
Development of more than 10 actinic keratoses    
Nausea (PUVA) Oral intake significantly decreased. A minimum of three doses should be trialled 2 (or higher)
More than 200 combined phototherapy treatments    

Apremilast

Required minimum dose of 30mg twice daily

Adverse event Brief description of minimum grade of toxicity National Institutes of Health
common toxicity criteria grade

Gastrointestinal

Diarrhoea

Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline

2 (or higher)

Nausea

Oral intake decreased without significant weight loss, dehydration or malnutrition

2 (or higher)

Vomiting

3 - 5 episodes (separated by 5 minutes) in 24 hrs

2 (or higher)

Abdominal pain

Moderate pain; limiting instrumental ADL

2 (or higher)

GORD

Moderate symptoms; medical intervention indicated

2 (or higher)

General Disorders/administrative site

Fatigue

Fatigue not relieved by rest; limiting instrumental ADL

2 (or higher)

Weight decrease

10 - <20% from baseline; nutritional support indicated

2 (or higher)

Immune System

Hypersensitivity

Intervention or interruption to treatment indicated; responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics); prophylactic medications indicated for <=24 hrs

2 (or higher)

Infections/infestations

Bronchitis

Moderate symptoms; oral intervention indicated (e.g., antibiotic, antifungal, antiviral)

2 (or higher)

Upper respiratory tract infection

Moderate symptoms; oral intervention indicated (e.g., antibiotic, antifungal, antiviral)

2 (or higher)

Decreased appetite

Oral intake altered without significant weight loss or malnutrition; oral nutritional supplements indicated

2 (or higher)

Musculoskeletal/connective tissue

Back pain

Moderate back pain; prescription analgesics indicated; limiting instrumental ADL

2 (or higher)

Nervous system

Migraine

Moderate pain; limiting instrumental ADL

2 (or higher)

Tension headache

Moderate pain; limiting instrumental ADL

2 (or higher)

Psychiatric

Insomnia

Moderate difficulty falling asleep, staying asleep or waking up early

2 (or higher)

Respiratory/thoracic/mediastinal

Cough

Moderate symptoms, medical intervention indicated; limiting instrumental ADL

2 (or higher)

Skin/subcutaneous tissue

Rash

Localized; local intervention indicated (e.g., topical antibiotic, antifungal, or antiviral)

2 (or higher)

Page last updated: 13 October 2022