Summary of the safety profile The most commonly reported adverse reactions (incidence ≥ 20%) are diarrhoea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anaemia.
The most frequently reported serious adverse reactions were pneumonia, colitis and diarrhoea. Tabulated list of adverse reactions The adverse reactions reported with duvelisib treatment are listed by system organ class and frequency in Table 2.
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2:
Adverse drug reactions reported in patients with haematologic malignancies receiving duvelisib (N=442) System organ class / preferred term or adverse reaction All grades Grade 3 or more Infections and infestations Lower respiratory tract infection1 Very common Common Sepsis Common Common Upper respiratory tract infection1 Very common Uncommon Blood and lymphatic system disorders Neutropenia1 Very common Very common Anaemia1 Very common Very common Thrombocytopenia1 Very common Very common Metabolism and nutrition disorders Decreased appetite Very common Uncommon Nervous system disorders Headache1 Very common Uncommon Respiratory, thoracic and mediastinal disorders System organ class / preferred term or adverse reaction All grades Grade 3 or more Dyspnoea1 Very common Common Pneumonitis2 Common Common Cough1 Very common Uncommon Gastrointestinal disorders Diarrhoea/Colitis3 Very common Very common Nausea1 Very common Uncommon Vomiting Very common Common Abdominal pain1 Very common Common Constipation Very common Uncommon Skin and subcutaneous tissue disorders Rash4 Very common Common Pruritus1 Common Uncommon Musculoskeletal and connective tissue disorders Musculoskeletal pain1 Very common Common Arthralgia Very common Uncommon General disorders and administration site conditions Pyrexia Very common Common Fatigue1 Very common Common Investigations Lipase increased Common Common Transaminases increased5 Very common Common 1 Grouped term for reactions with multiple preferred terms 2 Pneumonitis includes the preferred terms: pneumonitis, interstitial lung disease, lung infiltration 3 Diarrhoea or colitis includes the preferred terms: colitis, enterocolitis, colitis microscopic, colitis ulcerative, diarrhoea, diarrhoea haemorrhagic 4 Rash includes the preferred terms: dermatitis (including allergic, exfoliative, perivascular), erythema (including multiforme), rash (including exfoliative, erythematous, follicular, generalized, macular & papular, pruritic, pustular), toxic epidermal necrolysis and toxic skin eruption, drug reaction with eosinophilia and systemic symptoms, drug eruption, Stevens- Johnson syndrome.
5 Transaminase elevation includes the preferred terms: alanine aminotransferase increased, aspartate aminotransferase increased, transaminases increased, hypertransaminasaemia, hepatocellular injury, hepatotoxicity Note: Doses withheld for > 42 days due to treatment-related toxicity will result in permanent discontinuation from treatment Description of selected adverse reactions Infections The most common serious infections were pneumonia, sepsis, and lower respiratory infections.
Median time to onset of any grade infection was 3 months (range: 1 day to 32 months), with 75% of cases occurring within 6 months. Infections should be treated prior to initiation of duvelisib. Patients should be advised to report any new or worsening signs and symptoms of infection.
4. Diarrhoea and colitis The median time to onset of any grade diarrhoea or colitis was 4 months (range: 1 day to 33 months), with 75% of cases occurring by 8 months. 5 months (range: 1 day to 29 months; 75th percentile: 1 month). Patients should be advised to report any new or worsening diarrhea.
Non-infectious pneumonitis Median time to onset of any grade pneumonitis was 4 months (range: 9 days to 27 months), with 75% of cases occurring within 9 months. The median event duration was 1 month, with 75% of cases resolving by 2 months.
Duvelisib should be withheld in patients who present with new or progressive pulmonary signs and symptoms such as cough, dyspnoea, hypoxia, interstitial infiltrates on a radiologic exam, or a decline by more than 5% in oxygen saturation and evaluate for etiology.
If the pneumonitis is infectious, patients may be restarted on duvelisib at the previous dose once the infection, pulmonary signs and symptoms resolve. Severe cutaneous reactions Median time to onset of any grade cutaneous reaction was 3 months (range: 1 day to 29 months, 75th percentile: 6 months), with a median event duration of 1 month (range: 1 day to 37 months, 75th percentile: 2 months).
Severe cutaneous reactions include rash, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrosis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store