L04AX06 - Pomalidomide |
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, vomiting, diarrhea and constipation may potentially be porphyrinogenic through reduction in carbohydrate intake.
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. Common adverse reactions of pomalidomide that can be confused with an acute porphyric attack are nausea, vomiting, diarrhea and constipation. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Pomalidomide is a substrate of CYP1A2 and CYP3A4, and it is not an inducer or a mechanism-based inhibitor of CYP enzymes. No pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Isoindolones. Pomalidomide is an analogue of thalidomide.
Therapeutic characteristics
Pomalidomide has immunomodulatory and antineoplastic effect and is used in combination with corticosteroid in the treatment of multiple myeloma. Pomalidomide is more potent than both thalidomide (100 times) and Lenalidomide (10 times) (SPC).
It is administered orally.
Metabolism and pharmakokinetics
In vitro studies show that pomalidomide is mainly metabolized by CYP1A2 and 3A4, with minor contributions from CYP2C19 and CYP2D6 (Hoffmann 2013, Scott 2014). It is excreted primarily as metabolites in the urine. In vitro studies indicate that pomalidomide is a substrate of P-glycoprotein, and that it is not an inducer or inhibitor of CYP-enzymes (Kassera 2015).
References
- Scientific articles
- Hoffmann M, Kasserra C, et al. Absorption, metabolism and excretion of [14C]pomalidomide in humans following oral administration. Cancer Chemother Pharmacol. 2013 Feb;71(2):489-501 PMID 23203815. #4758
- Kasserra C, Assaf M, et al. Pomalidomide: Evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78 PMID 25159194. #4759
- Scott L. J. Pomalidomide: a review of its use in patients with recurrent multiple myeloma. 2014 Apr;74(5):549-62. PMID 24590685. #3144
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Imnovid). #3145
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