Uterine fibroid therapy: the pharmacokinetic considerations

Ali, Mohamed; Al-Hendy, Ayman

doi:10.1080/17425255.2018.1506766

Cited by 15 publications

(8 citation statements)

References 12 publications

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“… 32 , 33 Adolescent girls are particularly vulnerable to this condition because of the elevated iron request for rapid growth, and menstrual blood loss. 34 , 35 Furthermore, several conditions can play a determinant role in favoring insufficiency of iron in women, such as chronic gynecologic bleeding due to uterine fibroids, 36 - 38 endometriosis, 39 - 44 adenomyosis, or endometrial hyperplasia. Moreover, intestinal malabsorption problems, frequent blood donation, and benign and malignant gastrointestinal lesions are other causes of IDA in women.…”

Section: Iron Deficiency Anemia In Women Of Reproductive Agementioning

confidence: 99%

Iron Deficiency Anemia in Pregnancy: Novel Approaches for an Old Problem

Garzon

Cacciato

Certelli³

et al. 2020

Oman Med J

136

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Iron needs increase exponentially during pregnancy to meet the increased demands of the fetoplacental unit, to expand maternal erythrocyte mass, and to compensate for iron loss at delivery. In more than 80% of countries in the world, the prevalence of anemia in pregnancy is > 20% and could be considered a major public health problem. The global prevalence of anemia in pregnancy is estimated to be approximately 41.8%. Undiagnosed and untreated iron deficiency anemia (IDA) can have a great impact on maternal and fetal health. Indeed, chronic iron deficiency can affect the general wellbeing of the mother and leads to fatigue and reduced working capacity. Given the significant adverse impact on maternal-fetal outcomes, early recognition and treatment of this clinical condition is fundamental. Therefore, the laboratory assays are recommended from the first trimester to evaluate the iron status. Oral iron supplementation is the first line of treatment in cases of mild anemia. However, considering the numerous gastrointestinal side effects that often lead to poor compliance, other therapeutic strategies should be evaluated. This review aims to provide an overview of the current evidence about the management of IDA in pregnancy and available treatment options.

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Section: Iron Deficiency Anemia In Women Of Reproductive Agementioning

confidence: 99%

Iron Deficiency Anemia in Pregnancy: Novel Approaches for an Old Problem

Garzon

Cacciato

Certelli³

et al. 2020

Oman Med J

136

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“…org/ licen ses/ by-nc/4. 0/) vilaprisan [5,22]. Currently, further detailed mechanistic in vitro studies have been initiated, including investigations with liver microsomes, hepatocytes, and cytotoxicity tests under different cell culture conditions to support this hypothesis, and the results from these analyses will be published elsewhere.…”

Section: Digression: Hepatic Safety Of Vilaprisanmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of the Selective Progesterone Receptor Modulator Vilaprisan: A Comprehensive Overview

et al. 2021

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Vilaprisan is a highly potent selective progesterone receptor modulator in development for the treatment of symptomatic uterine fibroids and endometriosis. Its pharmacokinetics are characterized by rapid absorption, almost complete bioavailability, and dose-proportional exposure. The intrinsic factors of age, bodyweight, and race have no clinically relevant effect on the pharmacokinetics and pharmacodynamics of vilaprisan and do not warrant a dose adjustment. Similarly, vilaprisan can be used in patients with mild or moderate renal or hepatic impairment without dose adjustment, but its use is not recommended in patients with severe organ impairment. Vilaprisan has no perpetrator potential on cytochrome P450 (CYP) enzymes or transporters and therefore restrictions in the concomitant use of their substrates are not required. Nonetheless, because it is a sensitive CYP3A4 substrate itself, concomitant use of vilaprisan with strong CYP3A inhibitors or inducers is not recommended. However, there is no risk for QTc prolongation when vilaprisan and a strong CYP3A inhibitor are administered concomitantly, as indicated by a vilaprisan concentration-QTc response analysis across all studies with triplicate electrocardiogram measurements. Furthermore, due to its mode of action, vilaprisan is also not recommended to be used together with progestin-containing oral contraceptives. Vilaprisan shows a steep exposure-response relationship for inducing amenorrhea in patients with uterine fibroids experiencing heavy menstrual bleeding. Based on simulations, a dose of 2 mg/day is expected to induce a maximum bleeding reduction and was thus selected for phase III.

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“…84 Clinical trials with telapristone and onapristone were discontinued because of the liver safety issue. 44,85 Selective estrogen receptor modulator (SERM)…”

Section: Gnrh Antagonistmentioning

confidence: 99%

“…In clinical trials of telapristone in patients with uterine fibroids or endometriosis, clinically significant liver injury cases have been reported, and these studies were prematurely terminated because of this safety concern. 44,45 In another development program of onapristone for treatment of breast cancer, transient liver injury cases were observed during the treatment course, and thus the program was discontinued. 46,47 Sporadic cases of hepatic failure resulting in liver transplantation and/or death were reported following chronic use of ulipristal acetate in European countries where ulipristal acetate has been approved for the treatment of uterine fibroids.…”

Section: Drug-induced Liver Injury Potentialmentioning

confidence: 99%

“…Signals of hepatotoxicity were detected during the development of SPRMs. In clinical trials of telapristone in patients with uterine fibroids or endometriosis, clinically significant liver injury cases have been reported, and these studies were prematurely terminated because of this safety concern 44,45 . In another development program of onapristone for treatment of breast cancer, transient liver injury cases were observed during the treatment course, and thus the program was discontinued 46,47 .…”

Section: Drug‐induced Liver Injury Potentialmentioning

confidence: 99%

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