L04AC07 - Tocilizumab |
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 like nausea and vomiting may potentially be porphyrinogenic through reduction in carbohydrate intake.
Side effects
Infections are common in patients using immunosuppressants and since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended.Common adverse reactions of tocilizumab that can be confused with an acute porphyric attack are nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Antibody preparation with no CYP metabolism. Based on the pharmacokinetics, tocilizumab is not expected to have any porphyrinogenic effects.
Chemical description
Tocilizumab is a humanized monoclonal antibody against interleukin 6 receptor.
Therapeutic characteristics
Tocilizumab is used for the treatment of moderate to severe active rheumatoid arthritis in combination with methotrexate or as monotherapy. It is administered as an intravenous infusion.
Metabolism and pharmakokinetics
The metabolism of tocilizumab is expected to be similar as for endogenous antibodies, which are metabolised to peptides and amino acids in various body tissues and in plasma by circulating phagocytic cells or by their target antigen-containing cells.
Immunosuppressive treatment can reverse the down regulation of the expression of CYP enzymes (CYP 3A4, 1A2, 2C9 or 2C19) caused by inflammatory cytokines. This effect is not suspected to be porphyrinogenic as the CYP enzyme activity is not induced above a normal level.
References
- Scientific articles
- Keizer, R.J., Huitema, A.D.R., Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies. Clin Pharmacokinet. 2010 Aug 1;49(8):493-507 PMID 20608753. #4607
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Tocilizumab. Pharmaceutical Press 2009. #2989
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). RoActemra. #2988
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). RoActemra. #2990
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