bazedoxifene
Sources réglementaires consultées
Indications approuvées
- Traitement de l’ostéoporose postménopausique chez les femmes présentant un risque accru de fracture ; envisager d’autres options chez les patientes à risque élevé de fracture de la hanche.
Contre-indications
Absolues
- Thromboembolie veineuse active ou antérieure, notamment thrombose veineuse profonde, embolie pulmonaire ou thrombose veineuse rétinienne.
- Femmes en âge de procréer, grossesse ou allaitement, saignement utérin inexpliqué ou hypersensibilité.
Mises en garde cliniques
- Mise en garde majeure · Il augmente le risque de thromboembolie veineuse. Arrêter avant et pendant une immobilisation prolongée et ne reprendre qu’après récupération complète de la mobilité. — CIMA/AEMPS, ficha técnica 09511001
- Mise en garde majeure · L’utilisation n’est pas recommandée en cas d’insuffisance hépatique. L’expérience est insuffisante en cas d’insuffisance rénale sévère et le médicament doit être utilisé avec prudence. Explorer tout saignement utérin. — CIMA/AEMPS, ficha técnica 09511001
- Mise en garde majeure · Les doses supérieures à 20 mg par jour ne sont pas recommandées : elles n’ont pas montré d’efficacité supérieure et peuvent être associées à un risque supplémentaire. — CIMA/AEMPS, ficha técnica 09511001
Interactions médicamenteuses
- ModéréeInducteurs des UGT
Mécanisme: La rifampicine, le phénobarbital, la carbamazépine ou la phénytoïne peuvent réduire les concentrations de bazédoxifène.
Recommandation: Réévaluer l’efficacité et envisager d’autres options si l’association est nécessaire.
CIMA/AEMPS, ficha técnica 09511001https://cima.aemps.es/cima/dochtml/ft/09511001/FT_09511001.html
Effets indésirables
Communs (≥1%)
Bouffées de chaleur · Spasmes musculaires · Sécheresse buccale · Somnolence · Hypersensibilité
Rares mais graves
Thrombose veineuse profonde · Embolie pulmonaire · Thrombose veineuse rétinienne
Grossesse et allaitement
Indiqué uniquement chez les femmes ménopausées ; contre-indiqué chez les femmes en âge de procréer et ne doit pas être utilisé pendant la grossesse ou l’allaitement.
Bibliographie récente (PubMed)
Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM]). Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in
The prevalence of osteoporosis is increasing in the United States. To evaluate low bone mass and osteoporosis treatments to prevent fractures. Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. Bisphosphonates, denosumab, abalopara
Postmenopausal women commonly experience vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM). To evaluate effectiveness and harms of vaginal estrogen, nonestrogen hormone therapies, and vaginal moisturizers for treatment of GSM symptoms. Medline, Embase, and CINAHL through 11 December 2023. Randomized controlled trials (RCTs) of at least 8 weeks' duration enrolling postmenopausal women with at least 1 GSM symptom and reporting effectiveness or harms of hormonal interventions or vaginal moisturizers. Risk of bias and data extraction were performed by one reviewer and verified by a second reviewer. Certainty of evidence (COE) was assessed by one reviewer and verified by consensus. From 11 993 citations, 46 RCTs evaluating vaginal estrogen (k = 22), nonestrogen hormones (k = 16), vaginal moisturizers (k = 4), or multiple interventions (k = 4) were identified. Variation in populations, interventions, comparators, and outcomes precluded meta-analysis. Compared with placebo or no treatment, vaginal estrogen may improve vulvovaginal dryness, dyspareunia, most bothersome symptom, and treatment satisfaction. Compared with placebo, vaginal dehydroepiandrosterone (DHEA) may improve dryness, dyspareunia, and distress, bother, or interference from genitourinary symptoms; oral ospemifene may improve dryness, dyspareunia, and treatment satisfaction; and vaginal moisturizers may improve dryness (all low COE). Vaginal testosterone, systemic DHEA, vaginal oxytocin, and oral raloxifene or bazedoxifene may provide no benefit (low COE) or had uncertain effects (very low COE). Although studies did not report frequent serious harms, reporting was limited by short-duration studies that were insufficiently powered to evaluate infrequent serious harms. Most studies were 12 weeks or less in duration and used heterogeneous GSM diagnostic criteria and outcome measures. Few studies enrolled women with a history of cancer. Vaginal estrogen, vaginal
Hormone replacement therapy (HRT) is considered the gold standard for management of vasomotor and vaginal symptoms of menopause. Vasomotor symptoms of menopause may include hot flashes and diaphoresis that vary in intensity and duration. Other symptoms of menopause can include vaginal atrophy and dryness, leading to dyspareunia and increased risk of infection. These symptoms can be impactful on a woman's life and HRT has data to support its efficacy, however, HRT carries significant risks that are generally well known, including risk of stroke, cardiovascular disease, breast cancer, and venous thromboembolism. These risks were most well characterized by several landmark trials published in the early 2000s. There are several nuances to prescribing HRT that can make doing so complex. These include consideration of cyclic vs continuous administration and of tapering therapy. Additionally, estrogen is available in a variety of dosage forms including injections and transdermal formulations. However, for women with an intact uterus, estrogen will need to be combined with progestin or bazedoxifene (a selective estrogen receptor modulator - SERM), both once daily oral formulations, in order to minimize malignancy risk. Though product preference and considerations of dosing may vary depending on practitioner preference, this brief report aims to clarify some nuances to prescribing or recommending HRT.
Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti-inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S-adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy. These common or novel strategies for the reversal of chemoresistance promise to improve the treatment of CRC.