Monograph
L01FA02 - Ofatumumab |
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
Ofatumumab is a monoclonal human IgG1 antibody.
Therapeutic characteristics
Arzerra is indicated for the treatment of chronic lymphocytic leukaemia (CLL) in patients who are refractory to fludarabine and alemtuzumab.
Common side effects that can be confused with an acute porphyria attack are nausea, dorsal pain, ileal obstruction and diarrhoea. Other common side effects are lower and upper respiratory tract infection.
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
Irrelevant
Metabolism and pharmacokinetics
Ofatumumab is not metabolized by CYP-enzymes, but degraded by proteolytic enzymes to small peptides and individual amino acids (Keating 2012, Keizer 2010). It is being eliminated through a target-independent regulatory route and B-cell-mediated route (Guidetti 2012). Pharmacokinetic CYP-effects are not to be expected and there are no drug interactions observed consistent with such.
References
| # | Citation details | PMID |
|---|---|---|
| * | Scientific articles | |
| 1. | Cytokine-release syndrome: overview and nursing implications.
Breslin S. Clin J Oncol Nurs. 2007 Feb;11(1):37-42. |
17471824 |
| 2. | Immunological response as a source to variability in drug metabolism and transport.
Christensen H, Hermann M. Front Pharmacol. 2012;3:8. |
22363283 |
| 3. | Monoclonal antibodies for targeted treatment of lymphoproliferative neoplasias. 183-186. Ed. SessaC, Gianni L. et al. Hertfordshire, ESMO press, 2012.
Guidetti A, Giacomini A, et al. |
|
| 4. | Ofatumumab: a guide to its use in chronic lymphocytic leukaemia.
Keating GM, Lyseng-Williamsjon KA, et al. Drugs Ther Perspect. 2012;28(6):6-9. |
32226271 |
| 5. | Clinical pharmacokinetics of therapeutic monoclonal antibodies.
Keizer RJ, Huitema AD, et al. Clin Pharmacokinet. 2010 Aug;49(8):493-507. |
|
| 6. | CYP-mediated therapeutic protein-drug interactions: clinical findings, proposed mechanisms and regulatory implications.
Lee JI, Zhang L, et al. Clin Pharmacokinet. 2010 May;49(5):295-310 |
20384392 |
| * | Summary of Product Characteristics | |
| 7. | Norwegian medicines agency. Summary of Product Characteristics (SPC). Ofatumumab.
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