L02BG03 - Anastrozole |
Propably not porphyrinogenic |
PNP |
Rationale
Anastrozole has no progesterone, androgene or estrogen effects. It is an inhibitor of CYPs 1A2, 2C8/C9 and 3A4 in vitro, but hepatic exposure may be insignificant in vivo. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Anastrozole, a benzyltriazole derivative, is a selective, nonsteroidal aromatase inhibitor.
Therapeutic characteristics
Anastrozole is used in the treatment of advanced or locally advanced breast cancer, and as adjuvant treatment in hormone receptor-positive early breast cancer. It is administered orally. Common adverse reactions of anastrozole that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoea, and joint pain. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Hepatic exposure
Average steady state Cmax concentrations in patients in chronic treatment (1 mg/day) are 30-fold lower than the apparent Ki values determined in vitro, and hepatic expose may therefore be insignificant (Grimm, 1997).
Metabolism and pharmakokinetics
Extensively CYP-metabolized in the liver, only 10 per cent excreted as unchanged drug. Maximal plasma concetration in steady state about 100 ng/mL.
Anastrozole has been shown to inhibit in vitro metabolic reactions catalyzed by CYP1A2, 2C8/9, and 3A4, but only at relatively high concentrations. Although formal interaction studies have not been performed to date, it is considered unlikely that anastrozole, when administered at the recommended dosage, will result in clinically important interactions with drugs metabolized by CYP enzymes (Grimm, 1997).
Published experience
Anastrolsole was used uneventfully for 4 months in the treatment of breast cancer in 59 year old PV woman (Thiery-Vuillemin, 2008).
IPNet drug reports
Uneventful use reported in 3 patients 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." #3355
- Grimm SW, Dyroff MC. Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent and selective inhibitor of aromatase. Drug Metab Dispos. 1997;25(5):598-602. PMID 9152599. #2177
- Drug reference publications
- McEvoy GK, editor. Anastrozole. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (28.07.10). #2178
- Sweetman SC, editor. Martindale: The complete drug reference. Anastrozole. Pharmaceutical Press 2009. #3354
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Anastrozole Teva. #2179
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