Acute Porphyria Drug Database

L01FX03 - Catumaxomab
Not porphyrinogenic
NP

Rationale
No CYP-affinity. However, side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in carbohydrate intake.
Chemical description
Catumaxomab is a rodent hybrid monoclonal antibody.
Therapeutic characteristics
Catumaxomab is indicated for malignant ascites, secondary to epithelial cell adhesion molecule positive carcinoma where standard treatment is not available or not any longer possible. Common side effects that can be confused with an acute porphyria attack are nausea, vomiting, abdominal pain, diarrhoea, obstipation and dorsal pain. Other common side effects are infections and anorexia. A common side effect is cytokine release syndrome. Cytokines such as IL-1, IL-6 and TNF liberated in response to inflammation, infection of tissue destruction, modulate the expression of PXR, CAR, HNF-4 and NF-kB in a way to damp the hepatic expression of drug metabolizing CYP-genes (Breslin 2007, Christensen 2012). They also activate nitric oxide synhase-2 (NOS-2) which inhibit drug metabolizing CYPs directly via destabilization of the protein structure (Lee 2010).
Hepatic exposure
Insignificant and irrelevant
Metabolism and pharmacokinetics
Catumaxomab is not metabolized by CYP-enzymes, but are degraded to peptides and amino acids that can be re-used in the body for de novo synthesis of proteins or are excreted by the kidney (Keizer 2010).

References

  1. Scientific articles
  2. Breslin S. Cytokine-release syndrome: overview and nursing implications. Clin J Oncol Nurs. 2007 Feb;11(1):37-42. PMID 17471824. #2248
  3. Christensen H, Hermann M. Immunological response as a source to variability in drug metabolism and transport. Front Pharmacol. 2012;3:8. PMID 22363283. #2249
  4. Keizer RJ, Huitema AD, et al. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug;49(8):493-507. #3041
  5. Lee JI, Zhang L, et al. CYP-mediated therapeutic protein-drug interactions: clinical findings, proposed mechanisms and regulatory implications. Clin Pharmacokinet. 2010 May;49(5):295-310 PMID 20384392. #4738
  6. Summary of Product Characteristics
  7. Norwegian medicines agency. Summary of Product Characteristics (SPC). catumaksomab. #3043

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