FEZOLINETANT AS A NEW TREATMENT FOR MENOPAUSAL SYMPTOMS
STEVEN MALEN, PharmD, MBA
Dr. Steven Malen graduated with a dual degree: Doctor of Pharmacy (PharmD) and Master of Business Administration (MBA) from the University of Rhode Island. Over his career, he has worked as a clinical pharmacist in the retail, specialty, and compounding sectors. He specialized and taught on topics from vaccines to veterinary compounding. Dr. Malen has also written a science fiction novel and taught and co- founded the concept of Patient Empowered Blockchain (P.E.B.). Currently, Dr. Malen continues to write, teach, and consult various companies in the healthcare sector.
Menopausal vasomotor symptoms, such as hot flashes and night sweats, can significantly impact a patient's quality of life, prompting the need for effective and safe treatment options. This course explores fezolinetant, a selective neurokinin-3 receptor antagonist, as an alternative, innovative approach for alleviating menopausal vasomotor symptoms. Fezolinetant regulates body temperature by interacting with neurokinin-3 receptors. Clinical evidence and key trials have evaluated the efficacy and safety profile of fezolinetant. Practical considerations, such as dosing, potential drug interactions, adverse effects, and patient counseling strategies, are also discussed.
RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.
Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is
Pharmacy Technician 0669-0000-23-103-H01-T
Credits: 1 hour of continuing education credit
Type of Activity: Knowledge
Media: Internet/Home study Fee Information: $4.99
Estimated time to complete activity: 1 hour, including Course Test and course evaluation
Release Date: July 8, 2023 Expiration Date: July 8, 2026
Target Audience: This educational activity is for pharmacists.
How to Earn Credit: From July 8, 2023, through July 8, 2026, participants must:
Read the “learning objectives” and “author and planning team disclosures;”
Study the section entitled “educational activity;” and
Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)
Credit for this course will be uploaded to CPE Monitor®.
Learning Objectives: Upon completion of this educational activity, participants should be able to:
Describe the pharmacology of fezolinetant for treating menopausal vasomotor symptoms
Evaluate the clinical evidence supporting the effectiveness and safety of fezolinetant in reducing the frequency and severity of menopausal vasomotor symptoms
Describe fezolinetant’s potential drug interactions and adverse effects.
Learn patient counseling to safely use fezolinetant in managing menopausal vasomotor symptoms.
The following individuals were involved in developing this activity: Steven Malen, PharmD, MBA, and Pamela Sardo, PharmD, BS. Pamela Sardo, PharmD, BS, was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.
© RxCe.com LLC 2023: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.
Many women experience menopausal vasomotor symptoms such as hot flashes and night sweats during menopause. Their severity can vary greatly, with some women suffering significant symptoms that impact their quality of life. Fezolinetant was approved in May 2023 as a new treatment option for menopausal vasomotor symptoms. It regulates body temperature by interacting with neurokinin-3 receptors. For some patients, fezolinetant may provide another treatment option to relieve menopausal symptoms. By understanding the incidence, risk factors, and genetic influences related to hot flashes and night sweats, healthcare teams can effectively identify and manage these symptoms in menopausal women. In this course, pharmacists and pharmacy technicians are introduced to the use, effectiveness, and potential side effects of fezolinetant.
Epidemiology: Prevalence and Risk Factors
Menopause marks the cessation of a woman's menstrual periods as her body gradually produces lower levels of estrogen and progesterone.1-3 The onset of menopause is varied and multifaceted; however, the median age of natural menopause is reportedly 51 years.2,3 If menopause occurs between the ages of 40 to 45 years, it is considered early, and greater than 55 years is considered late.3
The more prominent symptoms of menopause are hot flashes and night sweats.1,4 Hot flashes and night sweats are vasomotor symptoms that commonly occur during menopause. Their cause is unknown, but they are possibly associated with the hypothalamus.1,4
Hot flash episodes are characterized by sudden sensations of heat, sweating, flushing, anxiety, and chills, typically lasting for 1 to 5 minutes.1,4,5 While hot flashes can cause significant distress, especially when severe and frequent, they are often overlooked due to their relatively benign nature.1
Vasomotor symptoms affect between 50-85% of women.1,4 The incidence and severity of menopausal symptoms tend to increase as women enter the transition phase toward menopause, marked by the onset of menstrual irregularities.1,6 The prevalence is highest during the late menopause transition phase, followed by a gradual decline.1,6
The mean duration of hot flashes has been estimated to be around 5.2 years, with some studies reporting a median duration of 7.4 years.1 Furthermore, approximately 25% of women continue to experience hot flashes even after 5 years of attaining menopause, and a significant proportion of women experience hot flashes even after 10 or 20 years of menopause.1 Hot flashes may present as night sweats, causing sleep disturbance.7
Various risk factors have been associated with an increased incidence of hot flashes. Obesity, African descent, lower socioeconomic status, premenstrual syndrome, sedentary lifestyle, and smoking have consistently been shown to be associated with hot flashes.7 Recent studies have also highlighted the role of genetic factors in the occurrence of hot flashes. For example, certain genetic variations in the tachykinin receptor 3 gene are significantly associated with menopausal vasomotor symptoms, including hot flashes.7 This is important since the tachykinin receptor 3 gene encodes the neurokinin-3 receptor,8 which is the receptor fezolinetant acts on.9
Management of Vasomotor Symptoms
The management approach for hot flashes and night sweats is directed by their severity, the presence of associated menopausal symptoms, the personal choice of the patient, and contraindications to hormone replacement therapy (HRT).1,7 Severity is graded as mild, moderate, or severe based on the degree of interference in the person’s daily activities.1,7 As mentioned above, night sweats can lead to sleep disturbances, possibly increasing the severity of the patient’s symptoms.1.7 Heat sensations may characterize mild menopausal vasomotor symptoms but without sweating.1 Moderate menopausal vasomotor symptoms usually include sweating, but the patient’s daily activities are not impacted greatly. In severe cases, the patient
experiences intense heat with sweating that disrupts activities; and, if night sweats are present, the patient will feel so hot as to require action, such as removing clothing or opening a window.1
Mild Symptoms: Lifestyle Modifications
For women experiencing mild hot flashes or night sweats, lifestyle modifications may be sufficient.1,5,6,10 Strategies such as using fans, lowering room temperature, drinking cool liquids, and avoiding triggers like alcohol, hot or spicy foods may be helpful. Wearing clothing that keeps the person cooler and is sweat-friendly may also mitigate symptoms;1,5,10 however, clinicians should be aware and advise patients that while lifestyle modification may be preferred, evidence is lacking that these changes improve hot flashes.11
Additional options with some effectiveness include weight loss, cognitive behavior therapy, and relaxation techniques.6,7 Low-dose Vitamin E has been evaluated as a therapy for hot flashes,7 but its efficacy has been questioned.6
Moderate to Severe Symptoms
In cases of moderate to severe symptoms, HRT is recommended as the first-line therapy.7,10,11 This involves hormone replacement with estrogen and/or progestogen. Estrogen alone may be used in women who have undergone hysterectomy, or estrogen combined with progestin (a synthetic form of progestogen) for women with a uterus. The choice of route (oral, transdermal, subcutaneous implant, or intravaginal) should be individualized in consultation with the patient.7 Transdermal formulations are preferred due to lower risks of certain complications. Progestins are added to prevent endometrial hyperplasia in women with a uterus.7
Special considerations are needed for women with breast cancer, as various factors may cause hot flashes.7,10-12 For example, studies of tamoxifen, a common breast cancer treatment drug, have reported that it is associated with hot flashes in up to 67% of patients.10 Moreover, HRT is contraindicated in women who are breast cancer survivors.7,10
There are risks associated with HRT, including an increased risk of heart attack, stroke, blood clots, gallbladder disease, and dementia.5,11,13 These risks are related to a patient’s physical health, age, and other characteristics.11,13
In cases where HRT is unsuitable or not tolerated, non-hormonal treatment options such as selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), and gabapentin can be considered.1,10 However, with breast cancer survivors who are taking tamoxifen, caution should be exercised with the use of SSRIs such as paroxetine since studies show that paroxetine inhibits the cytochrome P450 2D (CYP2D6) pathway and may be associated with higher mortality from breast cancer in patients who are taking tamoxifen.1,10 The degree to which an SSRI may inhibit CYP2D6 differs among the studies. In the case of fluoxetine, there is a consensus that it, and its metabolite, are strong inhibitors of CYP2D6.10 While no study has been published that shows a relationship between the use of fluoxetine and death from breast cancer among women taking tamoxifen (possibly due to the small sample sizes), fluoxetine may still not be safe when taken with tamoxifen.10
Overall, managing vasomotor symptoms in menopausal women requires a personalized approach, considering the severity of symptoms, associated conditions, risk-benefit analyses, and patient preferences, to provide effective relief and improve quality of life.6,7,10-13 Pharmacotherapy for hot flashes or night sweats may include the newly approved drug fezolinetant.
Fezolinetant as an Option for Managing Vasomotor Symptoms
As discussed above, hot flashes and night sweats are vasomotor symptoms characterized by sudden sensations of heat, sweating, flushing, anxiety, and chills. Hot flashes typically last 1 to 5 minutes. While HRT is considered an effective, first-line treatment for women, not all women should or can take hormone therapy due to their medical conditions, history, or preferences.7,13 Fezolinetant was approved as a treatment for vasomotor symptoms by the U.S. Food and Drug Administration (FDA) on May 12, 2023.14
After consultation with their healthcare providers, some women may choose fezolinetant for managing hot flashes and night sweats.
The effectiveness of VEOZAH® (fezolinetant) in treating moderate to severe vasomotor symptoms resulting from menopause was assessed in two phase-3 clinical trials.9 These trials consisted of a 12-week period where participants were randomly assigned to either fezolinetant or a placebo in a double-blind manner. After this initial period, the women who had received the placebo were re-randomized to receive fezolinetant for an additional 40 weeks, resulting in a total exposure of 52 weeks, to evaluate its safety over a longer duration.9
The trials, known as Trials 1 (NCT04003155) and 2 (NCT04003142), involved a total of 1022 women, with 522 participants in Trial 1 and 500 participants in Trial 2.9 These women experienced a minimum average of 7 moderate to severe vasomotor symptoms per day. They were randomly assigned to receive either fezolinetant at different doses, including a 45 mg strength or a placebo. The randomization process took into account their smoking status.9 The average age of the postmenopausal women participating in the study was 54 years. The majority of the participants identified themselves as Caucasian (81%), followed by African American (17%), Asian (1%), and Hispanic/Latina (24%). The study included menopausal women who had undergone a prior hysterectomy (32.1%), oophorectomy (21.6%), or had previous hormone therapy use (19.9%).9 Those who had been on hormone therapy underwent a wash-out period before participating in the trials.9
The main efficacy measures for both trials were the average change from baseline in the frequency and severity of moderate to severe vasomotor symptoms at Weeks 4 and 12.9 The data from each trial demonstrated a significant and clinically meaningful reduction in the frequency of moderate to severe vasomotor symptoms for those taking fezolinetant 45 mg compared to the placebo at Weeks 4 and 12.9 Additionally, there was a statistically
significant reduction in the severity of these symptoms at Weeks 4 and 12 for those taking fezolinetant 45 mg compared to the placebo.9
Overall, the results from these phase 3 clinical trials indicate that fezolinetant, particularly at a dosage strength of 45 mg, effectively reduces the frequency and severity of moderate to severe vasomotor symptoms experienced by menopausal women.9
Mechanism of Action
Fezolinetant is the first neurokinin 3 receptor antagonist approved by the FDA for treating vasomotor symptoms. By binding to and blocking the neurokinin 3 receptor, which is involved in the brain's regulation of body temperature, fezolinetant helps manage hot flashes and night sweats.9,15
The FDA has approved VEOZAH® (fezolinetant), an oral medication, that is designed to alleviate moderate to severe vasomotor symptoms.9 Vasomotor symptoms are most commonly characterized by hot flashes and night sweats related to menopause.1,9
The medication should be taken orally once a day with or without food, using liquids to aid swallowing, and the tablet should be swallowed whole without cutting, crushing, or chewing it.9 Taking fezolinetant at approximately the same time each day is recommended. If a dose is missed, but there are more than 12 hours until the next scheduled dose, the missed dose should be taken as soon as possible, and the regular schedule should be resumed the following day.9
Contraindications and Warnings
Fezolinetant is not recommended for use in women with certain conditions, including known cirrhosis, severe renal impairment, or end-stage renal disease, and when used concurrently with CYP1A2 inhibitors.9 It is important to conduct baseline bloodwork, including tests for serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and serum bilirubin (total and direct) before starting fezolinetant. Treatment should not be initiated if the concentrations of ALT or AST exceed two times the upper limit of normal (ULN) or if the total bilirubin is elevated based on the evaluating laboratory's criteria.9 Follow-up evaluations of hepatic transaminase concentration should be performed at 3 months, 6 months, and 9 months after starting therapy, as well as when symptoms of liver injury arise, such as nausea, vomiting, or yellowing of the skin or eyes.9
Side Effects or Adverse Events
The comparison of adverse reaction rates between different drugs or clinical trials is not straightforward due to variations in trial conditions.9 The safety of fezolinetant was assessed in three 52-week clinical trials involving a total of 1100 women. The first two trials had a placebo-controlled period of 12 weeks, followed by re-randomization of placebo recipients to fezolinetant for an additional 40 weeks.9 The third trial was a double-blind study evaluating the safety of fezolinetant over 52 weeks. The most frequently reported adverse reactions with fezolinetant 45 mg included abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated hepatic transaminases. In the combined data from all three trials, elevated hepatic transaminases occurred in a higher proportion of women (2.3%) exposed to fezolinetant 45 mg compared to the placebo group (0.9%).9
The CYP1A2 enzyme metabolizes fezolinetant, and it is metabolized to a lesser extent by CYP2C9 and CYP2C19. When fezolinetant is taken together with drugs that inhibit CYP1A2 (weak, moderate, or strong inhibitors), it can
lead to increased levels of fezolinetant in the blood.9 This interaction can result in higher maximum plasma concentrations (Cmax) and overall exposure (AUC) of fezolinetant. Therefore, the use of fezolinetant is contraindicated in individuals who are also taking CYP1A2 inhibitors.9 The most common CYP1A2 inhibitors include fluvoxamine, ciprofloxacin, enoxacin, and fluoroquinolones (such as norfloxacin).9 Other inhibitors include cimetidine, ticlopidine, amiodarone, and some selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and paroxetine.9 It is important to note that this is not an exhaustive list, and there may be other drugs or substances that can inhibit CYP1A2 activity.
Handling and Storage
Fezolinetant should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), with excursions allowed between 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines.9
Liver Enzyme Evaluation: Before starting fezolinetant and during treatment, the patient will need to undergo blood tests to assess the patient’s liver function. These tests will be conducted at 3 months, 6 months, and 9 months. Tests are also conducted if the patient experiences symptoms like nausea, vomiting, or yellowing of the skin or eyes. This is done to ensure proper liver function and to monitor for any potential abnormalities.9
Serious Adverse Reactions: It is important to be aware of possible serious adverse reactions associated with fezolinetant, including hepatic transaminase elevation. If a patient experiences any unusual symptoms or signs of liver problems, such as persistent nausea or abdominal pain, dark urine, or yellowing of the skin or eyes, the patient should promptly seek medical attention.9
Common Adverse Reactions: While taking fezolinetant, the patient may experience some less serious but common adverse reactions. These are listed with the most prevalent adverse reaction listed first and then in descending order: abdominal pain, diarrhea, insomnia, back pain, hot flashes, and hepatic transaminase elevation.9 These symptoms are generally manageable and should not cause alarm. However, if they become severe or bothersome, patients should discuss them with their healthcare provider. Pharmacists and staff should ask the patient if she is experiencing these reactions. If she is, the pharmacists should follow up with the patient and collaborate with the patient’s other primary healthcare providers if needed.
Drug Interactions: It is essential that the patient inform healthcare providers about all the medications, prescription and over-the-counter drugs, as well as any dietary supplements the patient is taking. Some drugs or supplements may interact with fezolinetant, potentially impacting its effectiveness or causing unwanted side effects. Providing a complete list of prescription and over-the-counter drugs to a healthcare provider helps ensure patient safety and provides information necessary to make any prudent treatment plan adjustments.9
Pharmacy Technicians: The integration of pharmacy technicians into pharmacy care teams contributes to the care of patients. Pharmacy technicians are ideally positioned to contribute to basic safe medication practices and to add to the patient record by medication history taking. Over-the-counter St. John's wort has been reported to inhibit cytochrome P4501A2.16 Certain medicinal cannabinoids have been reported to inhibit cytochrome P4501A2.17 Because fezolinetant is newly approved by the FDA, all possible drug interactions have not been identified. It remains to be determined whether the co-administration of these agents impacts fezolinetant. Because of the contraindication of fezolinetant with cytochrome P4501A2 inhibitors, if the pharmacy technician’s review of a patient’s medication history uncovers concomitant use of these or other products, the pharmacist should be
informed. If pharmacy technician practice setting and job descriptions permit, and neither employers nor the State Board of Pharmacy rules prohibit an action, technicians may participate in lifestyle discussions with patients.
If a patient has questions or concerns about the patient’s medication or experiences any unexpected symptoms, the patient should contact the pharmacist or other primary healthcare provider for guidance and support.
Interdisciplinary Approach and Collaboration
The primary role of the community pharmacist is often seen as focused on dispensing medications; however, the scope of clinical services that community pharmacies can provide has been expanding.18 The pharmacist is now encouraged to collaborate with a patient’s primary physician and other healthcare team members.18 The pharmacist serves as the “gatekeeper” for drugs used in treatment plans since they are the final individual to verify a medication order before it gets to the patient. Pharmacists are also well- positioned to collaborate in achieving a better outcome for patients.18 Pharmacists should be prepared to assist female patients seeking treatment for menopause. They should evaluate the risks and benefits of treatment options and contraindications of medications.11,13 They should also consider nonpharmacological approaches to manage hot flashes when appropriate.5,6,7,10-13
Menopause marks the cessation of a woman's menstrual periods as her body gradually produces lower levels of estrogen and progesterone. The more prominent symptoms of menopause are hot flashes and night sweats. Hot flashes and night sweats are vasomotor symptoms that commonly occur during menopause and are characterized by sudden sensations of heat, sweating, flushing, anxiety, and chills, typically lasting for 1 to 5 minutes. The cause of hot flashes and night sweats are unknown, but they are possibly associated with the hypothalamus.
Fezolinetant is a neurokinin-3 receptor antagonist developed as a non- hormonal therapy for menopause-associated vasomotor symptoms. It addresses the need for safe and effective, non-hormonal options. Fezolinetant targets the neuroendocrine circuits involved in vasomotor symptoms, providing a substantial reduction in symptoms and improving a patient’s quality of life. It is the most advanced neurokinin-3 receptor antagonist in clinical development and offers an alternative treatment option for menopause-related vasomotor symptoms.
While HRT is considered an effective, first-line treatment for women, not all women should or can receive hormone therapy due to their individual medical conditions, history, or preferences. After consultation with their healthcare providers, some women may choose fezolinetant for managing hot flashes and night sweats.
What percentage of menopausal women experience vasomotor symptoms?
Up to 65%
Between 50-85% of women
All women will experience hot flashes during menopause
How long do hot flashes typically last?
A few seconds
An hour or longer
1 to 5 minutes
10 to 15 minutes
Which of the following factors is NOT associated with an increased incidence of vasomotor symptoms?
What is the mean duration of hot flashes?
Which of the following is the first FDA-approved neurokinin 3 receptor antagonist for treating hot flashes?
How long is the recommended dosing interval for fezolinetant?
Once a week
Once a day
Twice a day
Three times a day
What adverse effect is among the reactions most frequently reported with the use of fezolinetant?
Elevated hepatic transaminases
Which enzyme primarily metabolizes fezolinetant?
A patient, a breast cancer survivor, asks the pharmacist about an alternative treatment to hormone replacement therapy to treat hot flashes. The patient is currently taking tamoxifen. Which of the following should the pharmacist recommend to the patient?
Consider taking paroxetine, an SSRI.
Consider taking fluoxetine, an SSRI.
Increase the patient’s dosage of tamoxifen to mitigate hot flashes.
Consider taking a selective norepinephrine reuptake inhibitor (SNRI) or gabapentin.
Fezolinetant is not recommended for use in women with
a history of breast cancer.
mild renal impairment.
a history of premenstrual syndrome.
Fraser GL, Lederman S, Waldbaum A, et al. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020;27(4):382-392. doi:10.1097/GME.0000000000001510
Gold EB. The timing of the age at which natural menopause occurs. Obstet Gynecol Clin North Am. 2011;38(3):425-440. doi:10.1016/j.ogc.2011.05.002
Madsen TE, Sobel T, Negash S, et al. A Review of Hormone and Non- Hormonal Therapy Options for the Treatment of Menopause. Int J Womens Health. 2023;15:825-836. Published 2023 May 25. doi:10.2147/IJWH.S379808
Mallhi TH, Khan YH, Khan AH, Mahmood Q, Khalid SH, Saleem M. Managing Hot Flushes in Menopausal Women: A Review. J Coll Physicians Surg Pak. 2018;28(6):460-465. doi: 10.29271/jcpsp.2018.06.460
National Institutes of Health. National Institute on Aging. Hot Flashes: What Can I Do?. NIH-NIA. 2021. https://www.nia.nih.gov/health/hot- flashes-what-can-i- do#:~:text=Hot%20flashes%2C%20a%20common%20symptom,flashe s%20interrupt%20their%20daily%20lives. Accessed on July 6, 2023.
Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes. 2005;3:47. Published 2005 Aug 5. doi:10.1186/1477-7525-
Bansal R, Aggarwal N. Menopausal Hot Flashes: A Concise Review. J Midlife Health. 2019;10(1):6-13. doi:10.4103/jmh.JMH_7_19
Saito S, Takahashi N, Maeno N, et al. An association study of tachykinin receptor 3 gene with schizophrenia in the Japanese population. Neuroreport. 2008;19(4):471-473. doi:10.1097/WNR.0b013e3282f600b4
Astellas Pharma US, Inc. VEOZAH (fezolinetant) tablets. Accessdata.fda.gov. 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216578s0 00lbl.pdf. Accessed on July 6, 2023.
Morrow PK, Mattair DN, Hortobagyi GN. Hot flashes: a review of pathophysiology and treatment modalities. Oncologist. 2011;16(11):1658-1664. doi:10.1634/theoncologist.2011-0174
Hill DA, Crider M, Hill SR. Hormone Therapy and Other Treatments for Symptoms of Menopause. Am Fam Physician. 2016;94(11):884-889.
Hickey M, Emery LI, Gregson J, Doherty DA, Saunders CM. The multidisciplinary management of menopausal symptoms after breast
cancer: a unique model of care. Menopause. 2010;17(4):727-733. doi:10.1097/gme.0b013e3181d672f6
Mehta J, Kling JM, Manson JE. Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts. Front Endocrinol (Lausanne). 2021;12:564781. Published 2021 Mar 26. doi:10.3389/fendo.2021.564781
Astellas. Astellas’ VEOZAHTM (fezolinetant) Approved by U.S. FDA for Treatment of Vasomotor Symptoms Due to Menopause. Astellas News Release. 2023. https://www.astellas.com/en/news/27756#:~:text=TOKYO%2C%20Ma y%2013%202023%20–
%20Astellas,menopause1%20on%20May%2012. Accessed on July 7, 2023.
Santoro N, Waldbaum A, Lederman S, et al. Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA). Menopause. 2020;27(12):1350-1356. doi:10.1097/GME.0000000000001621
Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther. 2000;294(1):88-95.
Alsherbiny MA, Li CG. Medicinal Cannabis-Potential Drug Interactions. Medicines (Basel). 2018 Dec 23;6(1):3. doi: 10.3390/medicines6010003
White A, Fulda KG, Blythe R, et al. Defining and enhancing collaboration between community pharmacists and primary care providers to improve medication safety. Expert Opin Drug Saf. 2022;21(11):1357-1364. doi:10.1080/14740338.2022.2147923
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