Monograph
L02AA02 - Polyestradiol Phosphate |
Propably not porphyrinogenic |
PNP |
Rationale
Neither polyestradiol phosphate nor its metabolite estradiol is listed as a mechanism based inhibitor of CYP2C9 or CYP3A4. Estradiol is listed as a weak inducer of CYP3A4, but no interactions with CYP-metabolism of other drugs are described for polyestradiol phosphate in clinical use. Estradiol used as add back therapy following the use of GnRH-agonists is reported to have caused attacks of acute porphyria in 3 women, but it has been reported used uneventfully by over 80 patients (primarily post-menopausal women), and polyestradiol phosphate is only indicated for use among men and postmenopausal women.
Chemical description
Polyestradiol phosphate is a polymeric ester of estradiol and phosphoric acid, with a prolonged duration of action.
Therapeutic characteristics
Polyestradiol phosphate is used in the treatment of metastatic prostatic carcinoma, and in the treatment of breast cancer in postmenopausal women. It is also used as substitution therapy in climacteric estrogen deficiency. It is administered as a long lasting deep intramuscular injection. In some preparations polyestradiol phosphat is given with mepivacaine to minimize pain at the site of injection. Mepivacaine is classified as PNP.
Metabolism and pharmacokinetics
After intramuscular injection polyestradiol phosphate is released slowly into the bloodstream where it is slowly metabolised to estradiol that enters the endogenous estradiol metabolism. Injection of polyestradiol phosphate was followed by rising plasma concentrations of estradiol in the first 2 weeks of treatment (Norlen, 1987). Estradiol is listed as a weak inducer of CYP 3A4 (Zhou, 2007; Rendic, 2002). Interactions with CYP-metabolism of other drugs are not described for polyestradiol phosphate in clinical use.
Published experience
Three reports of attacks of acute porphyria when estradiol only was used as add back therapy after GnRH-agonist treatment (Innala, 2010; Andersson, 2002). However, Andersson et al (2003) report that HRT containing estradiol or estradiol and progesterone (administered transdermally, orally or vaginally) have been used uneventfully in 48 postmenopausal AIP women.
IPNet drug reports
No reports received on the use of polyestradiol phosphate, however there are 38 reports on uneventful use of estradiol in patients with acute porphyria.
References
| # | Citation details | PMID |
|---|---|---|
| * | Scientific articles | |
| 1. | Andersson C, Nilsson, A et al. Atypical attack of acute intermittent porphyria - paresis but no abdominal pain. J Intern Med 2002; 252:265-270.
|
|
| 2. | Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448.
|
|
| 3. | Zhou, S.F., Xue, C.C., et al. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 2007; 29(6):687:710.
|
|
| 4. | Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden.
Andersson C, Innala E, et al. J Intern Med. 2003;254(2):176-83. |
12859699 |
| 5. | Evaluation of gonadotropin-releasing hormone agonist treatment for prevention of menstrual-related attacks in acute porphyria.
Innala E, Bäckström T, et al. Acta Obstet Gynecol Scand. 2010;89(1):95-100. |
20021268 |
| 6. | Plasma concentrations of estradiol and testosterone in single-drug polyestradiol phosphate therapy for prostatic cancer.
Norlen BJ, Fritjofsson A, et al. Eur Urol. 1987;13(3):193-7. |
3609099 |
| * | Drug reference publications | |
| 7. | Sweetman SC, editor. Martindale: The complete drug reference. Polyestradiol phosphate. Pharmaceutical Press 2009.
|
|
Similar drugs
Tradenames and packages
© NAPOS 2024