Summary of the safety profile Most patients taking thalidomide can be expected to experience adverse reactions. The most commonly observed adverse reactions associated with the use of thalidomide in combination with melphalan and prednisone are: neutropenia, leukopenia, constipation, somnolence, paraesthesia, peripheral neuropathy, anaemia, lymphopenia, thrombocytopenia, dizziness, dysaesthesia, tremor and peripheral oedema.
In addition to the adverse reactions outlined above, thalidomide in combination with dexamethasone in other clinical studies led to the very common adverse reaction of fatigue; common adverse reactions of transient ischaemic event, syncope, vertigo, hypotension, mood altered, anxiety, blurred vision, nausea and dyspepsia; and uncommon adverse reactions of cerebrovascular accident, diverticular perforation, peritonitis, orthostatic hypotension and bronchitis.
5). Tabulated list of adverse reactions Table 3 contains only the adverse reactions for which a causal relationship with medicinal product treatment could reasonably be established observed in the pivotal study and from post-marketing experience.
Frequencies given are based on the observations during a pivotal comparative clinical study investigating the effect of thalidomide in combination with melphalan and prednisone in previously untreated multiple myeloma patients. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); 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. g. fatal sepsis including septic shock)a, viral infections, including herpes zoster and hepatitis B virus reactivationa Neoplasms benign, malignant and unspecified (including cysts and polyps) Common Acute myeloid leukaemiab,c Uncommon Myelodysplastic syndromeb,c Not known Tumour lysis syndromea Blood and lymphatic system disorders Very common Neutropenia, leukopenia, anaemia, lymphopenia, thrombocytopenia Common Febrile neutropeniaa, pancytopeniaa Immune system disorders Not known Allergic reactions (hypersensitivity, angioedema, anaphylactic reaction, urticaria)a 14 System Organ Class Frequency Adverse reaction Endocrine disorders Not known Hypothyroidisma Psychiatric disorders Common Confusional state, depression Nervous system disorders Very common Peripheral neuropathyb, tremor, dizziness, paraesthesia, dysaesthesia, somnolence Common Convulsionsa, abnormal coordination Not known Posterior reversible encephalopathy syndrome (PRES)a,b, worsening of Parkinson’s disease symptomsa Ear and labyrinth disorders Common Hearing impaired or deafnessa Cardiac disorders Common Cardiac failure, bradycardia Uncommon Myocardial infarctiona, atrial fibrillationa, atrioventricular blocka Vascular disorders Common Deep vein thrombosisb Respiratory, thoracic and mediastinal disorders Common Pulmonary embolismb, interstitial lung disease, bronchopneumopathy, dyspnea Not known Pulmonary hypertensiona Gastrointestinal disorders Very common Constipation Common Vomiting, dry mouth Uncommon Intestinal obstructiona Not known Gastrointestinal perforationa, pancreatitisa, gastrointestinal haemorrhagea Hepatobiliary disorders Not known Hepatic disordersa Skin and subcutaneous tissue disorders Common Toxic skin eruption, rash, dry skin Not known Stevens-Johnson syndromea,b, toxic epidermal necrolysisa,b, drug reaction with eosinophilia and systemic symptomsa,b, leukocytoclastic vasculitisa Renal and urinary disorders Common Renal failurea Reproductive system and breast disorders Not known Sexual dysfunctiona, menstrual disorders including amenorrheaa General disorders and administration site conditions Very common Peripheral oedema Common Pyrexia, asthenia, malaise a Identified from post-marketing data.
8 “Description of selected adverse reactions”. c Acute myeloid leukaemia and myelodysplastic syndrome were reported in one clinical study in patients with previously untreated multiple myeloma receiving the combination of melphalan, prednisone and thalidomide (MPT).
Description of selected adverse reactions Blood and lymphatic system disorders Adverse reactions for haematological disorders are provided compared to the comparator arm, as the comparator has a significant effect on these disorders (Table 4).
3) * WHO criteria Additional adverse reactions from post-marketing experience with thalidomide and not seen in the pivotal study include febrile neutropenia and pancytopenia. Teratogenicity The risk of intra-uterine death or severe birth defects, primarily phocomelia, is extremely high.
6). Venous and arterial thromboembolic events An increased risk of venous […]