L04AC11 - Siltuximab |
Propably not porphyrinogenic |
PNP |
Important Information
Patients on immunosuppressive therapy have an increased risk of infections. Since infections have a potential to trigger acute porphyric attacks vigilance is motivated regarding signs or symptoms of infection and/or possible symptoms of a porphyric attack.
Side effects
Infections are common in patients using immunosuppressant drugs. Since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended. A common adverse reaction of siltuximab that can be confused with an acute porphyric attack is abdominal pain.
Rationale
Siltuximab is not metabolized by cytochrome P450 enzymes. No pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Siltuximab is a chimeric (human-murine) immunoglobulin G1kappa (IgG1kappa) monoclonal antibody.
Therapeutic characteristics
Siltuximab is used in the treatment of adult patients with multicentric Castlemans disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. Siltuximab is administered as an intravenous infusion.
Metabolism and pharmacokinetics
Siltuximab binds with high affinity to form stable complexes with the proinflammatory cytokine IL-6. In non-clinical studies, IL-6 is known to decreases the activity of CYP450. Treatment with siltuximab can reverse the down regulation of the expression of CYP enzymes (CYP 3A4, 1A2, 2C9 or 2C19) and may therefore increase the metabolism of CYP450 substrates. This effect is not suspected to be porphyrinogenic as the CYP enzyme activity is not induced above a normal level. Mechanisms for elimination of monoclonal antibodies are not well documented but are reported to include proteolysis by the liver and the reticuloendothelial system, target-mediated elimination and nonspecific endocytosis (Keizer 2010).
References
- Scientific articles
- Keizer RJ, Huitema AD et al. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug; 49 (8): 493-507. #3129
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Sylvant. #3140
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