Pomalid Adverse Reactions

Summary of the safety profile: Pomalidomide in combination with bortezomib and dexamethasone: The most commonly reported blood and lymphatic system disorders were neutropenia (46.8%), thrombocytopenia (36.7%) and anaemia (28.4%). The most frequently reported adverse reaction was peripheral sensory neuropathy (47.8%). The most commonly reported Grade 3 or 4 adverse reactions were blood and lymphatic system disorders including neutropenia (41.7%), thrombocytopenia (27.3%) and anaemia (14.0%). The most commonly reported serious adverse reaction was pneumonia (11.5%).
Other serious adverse reactions reported included pyrexia (4.0%), lower respiratory tract infection (2.9%), pulmonary embolism (2.9%), influenza (2.9%), and acute kidney injury (2.9%).
Pomalidomide in combination with dexamethasone: The most commonly reported adverse reactions in clinical studies have been blood and lymphatic system disorders including anaemia (45.7%), neutropenia (45.3%) and thrombocytopenia (27%); in general disorders and administration site conditions including fatigue (28.3%), pyrexia (21%) and oedema peripheral (13%); and in infections and infestations including pneumonia (10.7%). Peripheral neuropathy adverse reactions were reported in 12.3% of patients and venous embolic or thrombotic (VTE) adverse reactions were reported in 3.3% of patients. The most commonly reported Grade 3 or 4 adverse reactions were in the blood and lymphatic system disorders including neutropenia (41.7%), anaemia (27%) and thrombocytopenia (20.7%); in infections and infestations including pneumonia (9%); and in general disorders and administration site conditions including fatigue (4.7%), pyrexia (3%) and oedema peripheral (1.3%). The most commonly reported serious adverse reaction was pneumonia (9.3%). Other serious adverse reactions reported included febrile neutropenia (4.0%), neutropenia (2.0%), thrombocytopenia (1.7%) and VTE adverse reactions (1.7%).
Adverse reactions tended to occur more frequently within the first 2 cycles of treatment with pomalidomide.
Tabulated list of adverse reactions: Pomalidomide in combination with bortezomib and dexamethasone: In randomised study CC-4047-MM-007, 278 patients received pomalidomide, bortezomib and dexamethasone (Pom+Btz+Dex arm). See Dosage & Administration for dosing information.
The adverse reactions observed in patients treated with pomalidomide in combination with bortezomib and dexamethasone are listed in Table 10 by system organ class (SOC) and frequency for all adverse reactions and for Grade 3 or 4 adverse reactions.
Frequencies for Pom+Btz+Dex (any grade) are defined in accordance with current guidance, as: very common (≥1/10), common (≥1/100 to <1/10); and uncommon (≥1/1,000 to <1/100). (See Table 10.)


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Pomalidomide in combination with dexamethasone: In randomised study CC-4047-MM-003, 302 patients with relapsed and refractory multiple myeloma were exposed to 4 mg pomalidomide administered once daily for 21 days of each 28-day cycle in combination with a weekly low dose of dexamethasone.
The adverse reactions observed in patients treated with pomalidomide plus dexamethasone are listed as follows in Table 11 by system organ class (SOC) and frequency for all adverse reactions (ADRs) and for Grade 3 or 4 adverse reactions.
The frequencies of adverse reactions are those reported in the pomalidomide plus dexamethasone arm of study CC-4047-MM-003 (n = 302). Within each SOC and frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined in accordance with current guidance, as: very common (≥1/10), common (≥1/100 to <1/10); and uncommon (≥1/1,000 to <1/100). (See Table 11.)


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Tabulated list of post-marketing adverse reactions: In addition to the previously mentioned adverse reactions identified from the pivotal clinical trials, the following Table 12 is derived from data gathered from post-marketing surveillance. (See Table 12.)


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Description of selected adverse reactions: Teratogenicity: Pomalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects. Pomalidomide was found to be teratogenic in both rats and rabbits when administered during the period of major organogenesis (see Use in Pregnancy & Lactation and Pharmacology: Toxicology: Preclinical safety data under Actions). If pomalidomide is taken during pregnancy, a teratogenic effect of pomalidomide in humans is expected (see Precautions).
Neutropenia and thrombocytopenia: In patients receiving combination therapy with pomalidomide in clinical studies, neutropenia occurred in up to 46.8% of patients (41.7% Grade 3 or 4). Neutropenia did not lead to pomalidomide discontinuation in any patient and was infrequently serious.
Febrile neutropenia (FN) was reported in 3.2-6.7% of patients and was serious in 1.8-4.0% of patients (see Dosage & Administration and Precautions). In patients receiving combination therapy with pomalidomide in clinical studies, thrombocytopenia occurred in 27.0-36.7% of patients. Thrombocytopenia was Grade 3 or 4 in 20.7-27.3% of patients, led to pomalidomide discontinuation in 0.7% of patients and was serious in 0.4-1.7% of patients (see Dosage & Administration and Precautions).
Neutropenia and thrombocytopenia tended to occur more frequently within the first 2 cycles of treatment with pomalidomide.
Infection: Infection was the most common non haematological toxicity.
In patients receiving combination therapy with pomalidomide in clinical studies, infection occurred in 55.0-80.2% of patients (24.0-30.9% Grade 3 or 4). Upper respiratory tract infection and pneumonia were the most frequently occurring infections. Fatal infections (Grade 5) occurred in 2.7-4.0% of patients.
Infections led to pomalidomide discontinuation in 2.0-2.9% of patients.
Thromboembolic events: Prophylaxis with acetylsalicylic acid (and other anticoagulants in high risk patients) was mandatory for all patients in clinical studies. Anticoagulation therapy (unless contraindicated) is recommended (see Precautions).
In patients receiving combination therapy with pomalidomide in clinical studies, venous thromboembolic events (VTE) occurred in 3.3-11.5% of patients (1.3-5.4% Grade 3 or 4). VTE was reported as serious in 1.7-4.3% of patients, no fatal reactions were reported, and VTE was associated with pomalidomide discontinuation in up to 1.8% of patients.
Peripheral neuropathy: Pomalidomide in combination with bortezomib and dexamethasone: Patients with ongoing peripheral neuropathy ≥Grade 2 with pain within 14 days prior to randomisation were excluded from clinical trials. Peripheral neuropathy occurred in 55.4% of patients (10.8% Grade 3; 0.7% Grade 4). Exposure-adjusted rates were comparable across treatment arms. Approximately 30% of the patients experiencing peripheral neuropathy had a history of neuropathy at baseline. Peripheral neuropathy led to discontinuation of bortezomib in approximately 12.9% of patients, pomalidomide in 1.8% and dexamethasone in 2.2 - 8.9% of patients, respectively. Refer also to the bortezomib brochure/leaflet.
Pomalidomide in combination with dexamethasone: Patients with ongoing peripheral neuropathy ≥Grade 2 were excluded from clinical studies. Peripheral neuropathy occurred in 12.3% of patients (1.0% Grade 3 or 4). No peripheral neuropathy reactions were reported as serious, and peripheral neuropathy led to dose discontinuation in 0.3% of patients (see Precautions).
Haemorrhage: Haemorrhagic disorders have been reported with pomalidomide, especially in patients with risk factors such as concomitant medicinal products that increase susceptibility to bleeding. Haemorrhagic events have included epistaxis, intracranial haemorrhage and gastrointestinal haemorrhage.
Allergic reactions and severe skin reactions: Angioedema and severe cutaneous reactions including SJS, TEN and DRESS has been reported with the use of pomalidomide. Patients with a history of severe rash associated with lenalidomide or thalidomide should not receive pomalidomide (see Precautions).
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. Healthcare professionals are asked to report any suspected adverse reactions.