L02BG04 - Letrozole |
Propably not porphyrinogenic |
PNP |
Rationale
Letrozole has no progesterone, androgene or estrogen effects, and is not a mechanism based inhibitor of CYP2C9 or CYP3A4. No reports of CYP-inducing effects. However, side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Letrozole, a benzhydryltriazole derivative, is a selective, nonsteroidal aromatase inhibitor.
Therapeutic characteristics
Letrozole is used in the treatment of advanced or locally advanced breast cancer. It is administered orally. Common adverse reactions of letrozole that can be confused with an acute porphyric attack are nausea, vomiting, depression, diarrhea and constipation. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
Letrozole is metabolized in the liver by CYP3A4 and 2A6. In human liver microsomes, letrozole has been shown to strongly inhibit in vitro metabolic reactions catalyzed by CYP2A6 and to moderately inhibit reactions catalyzed by CYP2C19; thus, concomitant use of letrozole may result in decreased metabolism and increased plasma concentrations of agents metabolized by these hepatic microsomal enzymes. Negligible inhibitory effect on CYP2C9 and CYP3A (Jeong, 2009). No CYP-related interactions reported for the drug in clinical use.
Published experience
Letrolzole was used uneventfully in the treatment of breast cancer in 59 year old PV woman (Thiery-Vuillemin, 2008).
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.
References
- Scientific articles
- Thiery-Vuillemin, A, Chaigneau, L, et al. Anticancer therapy in patients with porphyrias: evidence today. Expert Opin Drug Saf 2008; 7(2):159-165. #1989
- Drug reference publications
- McEvoy GK, editor. Letrozole. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (28.07.10). #2181
- Sweetman SC, editor. Martindale: The complete drug reference. Letrozole. Pharmaceutical Press 2009. #2183
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Femar. #2182
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