S), respiratory arrest, myocardial infarction, arrhythmias, acute cardiac insufficiency and cardiac arrest have been observed. Severe anaphylactic and other hypersensitivity reactions, including anaphylactic shock and angioedema, have been reported following MabCampath administration. These symptoms can be ameliorated or avoided if premedication and dose escalation are utilised (see section 4.4).
Infections and infestations: Serious and sometimes fatal viral (e.g. adenovirus, parainfluenza, hepatitis B, progressive multifocal leukoencephalopathy (PML)), bacterial (including tuberculosis and atypical mycobacterioses, nocardiosis), protozoan (e.g. toxoplasma gondii), and fungal (e.g. rhinocerebral mucormycosis) infections, including those due to reactivation of latent infections have occurred during post-marketing surveillance. The recommended anti-infective prophylaxis treatment appears to be effective in reducing the risk of PCP and herpes infections (see section 4.4).
EBV-associated lymphoproliferative disorders, in some cases fatal, have been reported.
Blood and lymphatic system disorders: Severe bleeding reactions have been reported.
Immune system disorders: Serious and sometimes fatal autoimmune phenomena including autoimmune haemolytic anaemia, autoimmune thrombocytopenia, aplastic anaemia, Guillain Barré syndrome and its chronic form, chronic inflammatory demyelinating polyradiculoneuropathy have been reported. A positive Coombs test has also been observed. Fatal Transfusion Associated Graft Versus Host Disease (TAGVHD) has also been reported.
Metabolism and nutritional disorders: Tumour lysis syndrome with fatal outcome has been reported.
Nervous system disorders: Intracranial haemorrhage has occurred with fatal outcome, in patients with thrombocytopenia.
Cardiac disorders: Congestive heart failure, cardiomyopathy, and decreased ejection fraction have been reported in patients previously treated with potentially cardiotoxic agents.
4.9 Overdose
Patients have received repeated unit doses of up to 240 mg of MabCampath. The frequency of grade 3 or 4 adverse events, such as fever, hypotension and anaemia, may be higher in these patients. There is no known specific antidote for MabCampath. Treatment consists of discontinuation of MabCampath and supportive therapy.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC04.
Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 21-28 kD lymphocyte cell surface glycoprotein (CD52) expressed primarily on the surface of normal and malignant peripheral blood B and T cell lymphocytes. Alemtuzumab was generated by the insertion of six complementarity-determining regions from an IgG2a rat monoclonal antibody into a human IgG1 immunoglobulin molecule.
Alemtuzumab causes the lysis of lymphocytes by binding to CD52, a highly expressed, non-modulating antigen which is present on the surface of essentially all B and T cell lymphocytes as well as monocytes, thymocytes and macrophages. The antibody mediates the lysis of lymphocytes via complement fixation and antibody-dependent cell mediated cytotoxicity. The antigen has been found on a small percentage (< 5%) of granulocytes, but not on erythrocytes or platelets. Alemtuzumab does not appear to damage haematopoietic stem c |
