Summary of the safety profile The safety profile of ADCETRIS is based on available clinical trial data, the Named Patient Program (NPP), and post-marketing experience to date. Frequencies of adverse reactions described below and in Table 7 have been determined based on data generated from clinical studies.
1) the most frequent adverse reactions (≥ 10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhoea, pyrexia, neutropenia, upper respiratory tract infection, arthralgia, rash, cough, vomiting, pruritus, peripheral motor neuropathy, infusion-related reactions, constipation, dyspnoea, myalgia, weight decreased, and abdominal pain.
Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was ≤ 1%. Adverse events led to treatment discontinuation in 24% of patients receiving ADCETRIS. 1) were consistent with those observed in the combined pivotal phase 2 studies, with the exception of peripheral motor neuropathy, which had a higher incidence (28% vs.
9% in the pivotal phase 2 studies) and was primarily Grade 2. Patients also had a higher incidence of arthralgia, Grade 3 anaemia, and back pain compared to patients observed in the combined pivotal phase 2 studies. 1) were consistent with the safety profile of the pivotal clinical studies.
Combination therapy (AVD/CHP) For safety information of chemotherapy agents given in combination with ADCETRIS (doxorubicin, vinblastine and dacarbazine (AVD) or cyclophosphamide, doxorubicin and prednisone (CHP)), refer to their summary of product characteristics.
In the studies of ADCETRIS as combination therapy in 662 patients with previously untreated advanced HL (C25003) and 223 patients with previously untreated CD30+ peripheral T-cell lymphoma (PTCL) (SGN35-014), the most common adverse reactions (≥ 10%) were: infections, neutropenia, peripheral sensory neuropathy, nausea, constipation, vomiting, diarrhoea, fatigue, pyrexia, alopecia, anaemia, weight decreased, stomatitis, febrile neutropenia, abdominal pain, decreased appetite, insomnia, bone pain, rash, cough, dyspnoea, arthralgia, myalgia, back pain, peripheral motor neuropathy, upper respiratory tract infection, and dizziness.
In patients receiving ADCETRIS combination therapy, serious adverse reactions occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (15%), pyrexia (5%), and neutropenia (3%).
Adverse events led to treatment discontinuation in 10% of patients. Adverse events that led to treatment discontinuation in ≥ 2% of patients included peripheral sensory neuropathy, and peripheral neuropathy. Tabulated list of adverse reactions Adverse reactions for ADCETRIS are listed by MedDRA System Organ Class and Preferred Term (see Table 7).
Within each System Organ Class, adverse reactions are listed under frequency categories of: 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); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 7:
Adverse reactions to ADCETRIS System organ class Adverse reactions (monotherapy) Adverse reactions (combination therapy) Infections and infestations Very common: Infectiona, upper respiratory tract infection Infectiona, upper respiratory tract infection Common: Herpes zoster, pneumonia, herpes simplex, oral candidiasis Pneumonia, oral candidiasis, sepsis/septic shock, herpes zoster Uncommon: Pneumocystis jiroveci pneumonia, staphylococcal bacteraemia, cytomegalovirus infection or reactivation, sepsis/septic shock Herpes simplex, Pneumocystis jiroveci pneumonia Not known: Progressive multifocal leukoencephalopathy Blood and lymphatic system disorders Very common: Neutropenia Neutropeniaa, anaemia, febrile neutropenia Common: Anaemia, thrombocytopenia Thrombocytopenia Uncommon: Febrile neutropenia Immune system disorders Uncommon: Anaphylactic reaction Anaphylactic reaction Metabolism and nutrition disorders Very common: Decreased appetite Common: Hyperglycaemia Hyperglycaemia Uncommon: Tumour lysis syndrome Tumour lysis syndrome Psychiatric disorders Very common: Insomnia Nervous system disorders Very common: Peripheral sensory neuropathy, peripheral motor neuropathy Peripheral sensory neuropathya, peripheral motor neuropathya, dizziness Common: Dizziness Uncommon: Demyelinating polyneuropathy Respiratory, thoracic and mediastinal disorders Very common: Cough, dyspnoea Cough, dyspnoea Gastrointestinal disorders Very common: Nausea, diarrhoea, vomiting, constipation, abdominal pain Nausea, constipation, vomiting, diarrhoea, abdominal pain, stomatitis Uncommon: Pancreatitis acute Pancreatitis acute Hepatobiliary disorders Common: Alanine aminotransferase/aspartate aminotransferase (ALT/AST) increased Alanine aminotransferase/aspartate aminotransferase (ALT/AST) increased Skin and subcutaneous tissue disorders Very common: Rasha, pruritus Alopecia, rasha Common: Alopecia Pruritus Uncommon: Stevens-Johnson syndrome/toxic epidermal necrolysis Stevens-Johnson syndromeb Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS) Musculoskeletal and connective tissue disorders Very common: Arthralgia, myalgia Bone pain, […]