Clinical Pharmacodynamics of Anticancer Drugs
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Medroxyprogesterone acetate is commonly used for second-line endocrine therapy in advanced breast cancer. Evaluation of medroxyprogesterone acetate pharmacokinetics in 129 patients with advanced breast cancer demonstrated wide interpatient variability in minimum Css.100 Medroxyprogesterone acetate concentrations were higher in the 45 patients who developed medroxyprogesterone acetate-related side effects (median toxic 81 ng/ml vs. nontoxic 32 ng/ml). Objective response was assessable in 55 patients treated with medroxyprogesterone acetate monotherapy. Plasma medroxyprogesterone acetate concentrations were significantly lower in the patients with progressive disease than those with complete response, partial response, or stable disease (median 46 ng/ml and 65 ng/ml, respectively). Medroxyprogesterone acetate dosage was not significantly related to toxicity or response in this study.
Development of palliative medicine in the United Kingdom and Ireland
Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita in Textbook of Palliative Medicine and Supportive Care, 2015
Progestational agents are reasonably well tolerated for the most part. However, adverse effects of both megestrol acetate and medroxyprogesterone include thromboembolic phenomena, breakthrough uterine bleeding, peripheral edema, hyperglycemia, hypertension, adrenal suppression, and adrenal insufficiency.  2 The risk of thromboembolic events with the use of megestrol acetate is minimal. In Pascual Lopez et al.'s meta-analysis, the only statistically significant adverse effect observed in patients receiving megestrol acetate versus placebo was edema with a relative risk of 1.67. 52 However, a history of thromboembolism remains a definite contraindication to initiating megestrol acetate for the anorexia/weight loss syndrome, as the risk: benefit ratio is too great. Whereas use of progestational agents for the anorexia/weight loss syndrome in cancer or HIV patients may provide benefit, their use in weight-losing congestive heart failure has not been extensively studied. Progestational agents promote fluid retention and may therefore lead to deleterious side effects in this particular patient group. In general, their use in congestive heart failure patients is not routinely recommended.
Endocrine Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
MPA is well absorbed orally, with blood levels peaking after 2–4 hours and a half-life of 12–17 hours. It can also be administered in a depot form (i.e., Depo-ProveraTM) by deep intramuscular injection (normally into the gluteal muscle) which provides a half-life of 40–50 days. As with most progestogens, side effects include GI disturbances (e.g., nausea), cardiovascular abnormalities (e.g., hypertension, palpitation, congestive heart failure), depression, fluid retention, breast and menstrual cycle irregularities in women, alopecia, sexual dysfunction, skin reactions, and weight changes. In addition to these general adverse effects, the glucocorticoid effects associated with MPA can lead to Cushingoid syndrome at higher doses. Also, rarely, vision disorders such as retinal thrombosis can occur, in which case treatment should be immediately discontinued. Medroxyprogesterone acetate should be avoided during conception or pregnancy, as genital malformations in the fetus may occur.
Investigational PI3K/AKT/mTOR inhibitors in development for endometrial cancer
Published in Expert Opinion on Investigational Drugs, 2019
Fabio Barra, Giulio Evangelisti, Lorenzo Ferro Desideri, Stefano Di Domenico, Domenico Ferraioli, Valerio Gaetano Vellone, Franco De Cian, Simone Ferrero
In general, HT is indicated for women with advanced or recurrent EC and endometrioid histology in presence of not rapidly progressive disease. As it has a more favorable toxicity-profile, it is especially suitable for women with poor physical condition [30,31]. Progestogens (such as medroxyprogesterone acetate) are generally employed in this setting. In a randomized trial, the RR observed in patients with EC characterized by positivity for estrogen (ER) and progestogens receptors (PR) undergoing HT was 25% and 37%, respectively (versus 7–8% for patients with ER/PR negative disease) [30,31]. Based on these results, the positivity of ER and/or PR is considered a predictive factor for HT response; thus, their accurate histopathologic assessment should be routinely performed before starting HT [21]. However, several trials on the use of other hormonal therapies, such as tamoxifen, anastrozole, and fulvestrant, demonstrated only modest activity (RRs of approximately 10%) in the treatment of patients with advanced or recurrent EC [32–35].
Progestin or anti-estrogen treatment for endometrial cancer: choosing the best option for selected patients
Published in Gynecological Endocrinology, 2021
Marta Caretto, Tommaso Simoncini
Fertility-sparing treatments should be restricted to women with atypical hyperplasia/endometrioid intra-epithelial neoplasia (AH/EIN) or grade 1 endometrioid carcinoma without myometrial invasion. Hysteroscopic resection followed by the progestin therapy achieve the highest complete remission rate according to recent literature. The progestin therapy includes oral progestin as well as intrauterine progestin application. Medroxyprogesterone acetate (400–600 mg/day) or megestrol acetate (160–320 mg/day) are the recommended oral treatments [3]. Only patients undergoing oral treatment should be informed of major risks or the presentation of systemic adverse effects. Instead, in case of the intrauterine progestin therapy such as levonorgestrel-releasing intrauterine system combined with gonadotropin-releasing hormone receptor agonist or progestin a satisfactory pregnancy rate and a low recurrence rate have been reported. The combination of levonorgestrel intrauterine device with oral progestins with or without gonadotropin-releasing hormone analogs can also be considered. There is a lack of evidence for anti-estrogenic treatment in women who wish to preserve fertility [4].
Analysis of prescribing error and pharmacist’s intervention on obstetrics and gynaecology outpatient prescriptions in a Malaysian tertiary hospital
Published in Journal of Obstetrics and Gynaecology, 2022
Jeevanandan Narayanan, Shamala Balan, Ong Li Ling, Nurhamizah Kasim, Prcella Johny
Of the 3883 prescriptions screened, prescribing error was identified in 359 prescriptions (9.2%) (Table 1). The number of prescriptions with error of commission was found to be more prevalent (n = 188, 52.4%), which were mostly due to wrong or inappropriate duration and dose (n = 47, 11.8%, respectively). Thirteen prescriptions were intervened for wrong or inappropriate duration prescribed for tablet medroxyprogesterone, 5 mg. Another 14 interventions were recorded in the same category where the duration of prophylactic anticoagulant therapy prescribed to postnatal patients were either inadequate or more than required. Besides this, the study also showed that 6.1% of the prescriptions contained non-formulary drugs, of which 45.8% were for obstetric supplements; i.e.vitamin D 800 IU and Obimin®.
Related Knowledge Centers
- Active Metabolite
- Androgen Receptor
- Antiandrogen
- Organic Compound
- Progesterone
- Steroid
- Progestogen
- Medroxyprogesterone Acetate
- Pregnane
- 17Α-Hydroxyprogesterone