Yuvafem - Drug Monograph

Introduction

Yuvafem (estradiol vaginal insert) is a low-dose, locally-acting estrogen therapy approved for the treatment of atrophic vaginitis due to menopause. It provides targeted relief of urogenital symptoms while minimizing systemic estrogen exposure, making it a favorable option for patients seeking localized treatment of vaginal atrophy.

Mechanism of Action

Yuvafem contains 17β-estradiol, which is identical to endogenous human estrogen. It acts locally on estrogen receptors in vaginal tissue, reversing atrophic changes by:

• Increasing vaginal epithelial cell maturation
• Restoring vaginal pH to premenopausal levels
• Improving vaginal blood flow and lubrication
• Enhancing tissue elasticity and integrity

The low-dose formulation (10 mcg) is designed to provide local effects with minimal systemic absorption.

Indications

Yuvafem is FDA-approved for:

• Treatment of moderate to severe vaginal dryness and pain with intercourse (dyspareunia) due to menopause
• Management of symptoms of vulvar and vaginal atrophy

Dosage and Administration

• Remove from blister pack using dry hands
• Insert digitally or with applicator high into the vagina
• Administer at approximately the same time each dosing day
• May be used day or night
• Continue therapy based on symptom response

• Renal impairment: No dosage adjustment required
• Hepatic impairment: Use with caution in patients with liver disease
• Geriatric patients: No specific dosage adjustment recommended

Pharmacokinetics

Contraindications

• Known or suspected breast cancer
• Known or suspected estrogen-dependent neoplasia
• Undiagnosed abnormal genital bleeding
• Active or history of venous thromboembolism (DVT, PE)
• Active or recent arterial thromboembolic disease
• Known hypersensitivity to estradiol or any product components
• Liver dysfunction or disease
• Known protein C, protein S, or antithrombin deficiency

Warnings and Precautions

• Cardiovascular risk: Possible increased risk of cardiovascular events and stroke
• Malignancy risk: Increased risk of breast and ovarian cancer
• Dementia: Increased risk in women ≥65 years old
• Gallbladder disease: Increased risk of requiring gallbladder surgery
• Visual abnormalities: May induce retinal vascular thrombosis
• Hypercalcemia: Monitor in patients with breast cancer and bone metastases
• Severe hypersensitivity: Discontinue if anaphylactic reaction occurs

Drug Interactions

• Rifampin, carbamazepine, St. John's wort - may decrease estradiol levels

• Ketoconazole, ritonavir - may increase estradiol levels

• Thyroid hormone replacement therapy - may decrease TSH levels
• Warfarin - may alter anticoagulant effect
• Corticosteroids - increased corticosteroid effects

Adverse Effects

• Headache
• Breast tenderness
• Vaginal discharge
• Abdominal pain
• Back pain

• Nausea
• Diarrhea
• Urinary tract infection
• Vaginal discomfort
• Vulvovaginal pruritus

• Venous thromboembolism
• Stroke
• Myocardial infarction
• Breast cancer
• Endometrial cancer
• Gallbladder disease
• Severe allergic reactions

Monitoring Parameters

• Complete medical and family history
• Physical examination including breast and pelvic exam
• Blood pressure measurement
• Lipid profile consideration
• Liver function tests if indicated

• Annual breast examination and mammogram
• Regular pelvic examinations
• Symptom assessment and treatment response
• Blood pressure monitoring
• Evaluation for any unusual vaginal bleeding
• Assessment of need for continued therapy

Patient Education

• Use exactly as prescribed (twice weekly after initial daily dosing)
• Report any unusual vaginal bleeding immediately
• Perform regular breast self-examinations
• Attend scheduled mammograms and clinical breast exams
• Recognize signs of blood clots (leg pain, chest pain, shortness of breath)
• Understand potential drug interactions
• Store at room temperature away from moisture
• Use non-hormonal contraception if premenopausal
• Report any visual changes or severe headaches

• Wash hands before and after administration
• May use during menstrual periods
• Continue therapy even during intercourse
• Contact healthcare provider if symptoms persist or worsen

References

1. FDA Prescribing Information: Yuvafem (estradiol vaginal inserts) 2. The North American Menopause Society. (2020). The 2020 hormone therapy position statement of The North American Menopause Society. Menopause, 27(11), 1362-1387. 3. Suckling J, Lethaby A, Kennedy R. (2006). Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev, 2006(4):CD001500. 4. Bachmann G, Lobo RA, Gut R, et al. (2008). Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Obstet Gynecol, 112(5):1053-1060. 5. Simon JA, Lin VH, Radovich C, et al. (2010). One-year long-term safety study of a low-dose estradiol vaginal tablet. Obstet Gynecol, 116(4):876-883.