Minivelle
estradiol · Film, Extended Release · Transdermal
Uses
1 INDICATIONS AND USAGE MINIVELLE is indicated for: MINIVELLE® is an estrogen indicated for: Treatment of moderate to severe vasomotor symptoms due to menopause ( 1.1 ) Prevention of postmenopausal osteoporosis ( 1.2 ) Limitations of Use When prescribing solely for the treatment of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis. 1.1 Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause 1.2 Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis. 1.1 Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause 1.2 Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.
Dosage and administration
Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, consider addition of a progestogen to reduce the risk of endometrial cancer. Generally, a woman without a uterus, does not need to use a progestogen in addition to her estrogen therapy. In some cases, however, hysterectomized women who have a history of endometriosis may need a progestogen [see Warnings and Precautions ( 5.2 , 5.14 )] . Use estrogen-alone, or in combination with a progestogen, at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary. Start therapy with MINIVELLE® 0.0375 mg per day applied to the skin twice weekly for the treatment of moderate to severe vasomotor symptoms due to menopause. Dosage adjustment should be guided by the clinical response ( 2.1 ) Start therapy with MINIVELLE 0.025 mg per day applied to the skin twice weekly for the prevention of postmenopausal osteoporosis. The dose may be adjusted as necessary ( 2.2 ) Place MINIVELLE on a clean, dry area on the lower abdomen (below the umbilicus) or buttocks. Do not apply MINIVELLE to the breasts ( 2.3 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with MINIVELLE 0.0375 mg per day applied to the skin twice weekly. Make dosage adjustments based on clinical response. Attempt to taper or discontinue MINIVELLE at 3 to 6 month intervals. 2.2 Prevention of Postmenopausal Osteoporosis due to Menopause 2.3 Application Instructions Place the adhesive side of MINIVELLE on a clean, dry area on the lower abdomen (below the umbilicus) or buttocks. Do not apply MINIVELLE to the breasts. Replace MINIVELLE twice weekly (every 3-4 days). Rotate the sites of application, with an interval of at least 1 week allowed between applications to a particular site. Select an area for application that is not oily, damaged, or irritated. Avoid the waistline, since tight clothing may rub the system off. Apply the system immediately after opening the pouch and removing the protective liner. Press the system firmly in place with the palm of the hand for about 10 seconds, making sure there is good contact with the skin, especially around the edges. In the event that a system falls off, reapply the same system or apply a new system to another location. In either case, continue the original treatment schedule. If a woman has forgotten to apply MINIVELLE, have her apply a new system as soon as possible. Apply the new system on the original treatment schedule. The interruption of treatment in women taking MINIVELLE might increase the likelihood of breakthrough bleeding, spotting and recurrence of symptoms.
Dosage forms and strengths
Transdermal system: 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day, and 0.1 mg/day. Transdermal system: 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day, and 0.1 mg/day ( 3 )
Contraindications
4 CONTRAINDICATIONS MINIVELLE is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding [see Warnings and Precautions ( 5.2 )] . Breast cancer or a history of breast cancer [see Warnings and Precautions ( 5.2 )] . Estrogen-dependent neoplasia [see Warnings and Precautions ( 5.2 )] . Active DVT, PE, or a history of these conditions [see Warnings and Precautions ( 5.1 )] . Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions [see Warnings and Precautions ( 5.1 )] . Known anaphylactic reaction, angioedema, or hypersensitivity to MINIVELLE Hepatic impairment or disease Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders Undiagnosed abnormal genital bleeding ( 4 , 5.2 ) Breast cancer or a history of breast cancer ( 4 , 5.2 ) Estrogen-dependent neoplasia ( 4 , 5.2 ) Active DVT, PE, or a history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions ( 4 , 5.1 ) Known anaphylactic reaction, angioedema, or hypersensitivity to MINIVELLE ( 4 ) Hepatic impairment or disease ( 4 , 5.10 ) Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )
Warnings and precautions
Estrogens increase the risk of gallbladder disease ( 5.4 ) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.5 , 5.6 , 5.9 , 5.10 ) Monitor thyroid function in women on thyroid replacement therapy ( 5.11 , 5.18 ) 5.1 Cardiovascular Disorder Increased risks of stroke and DVT are reported with estrogen-alone therapy. Increased risks of PE, DVT, stroke and MI are reported with estrogen plus progestin therapy. Immediately discontinue estrogen with or without progestogen therapy if any of these occur or are suspected. Manage appropriately any risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus). Stroke The WHI estrogen-alone substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 strokes per 10,000 women-years, respectively). The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies ( 14.3 )] . Immediately discontinue estrogen-alone therapy if a stroke occurs or is suspected. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years). 1 The WHI estrogen plus progestin substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 strokes per 10,000 women-years, respectively) [see Clinical Studies, ( 14.3 )] . The increase in risk was demonstrated after the first year and persisted. 1 Immediately discontinue estrogen plus progestogen therapy if a stroke occurs or is suspected. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years). 1 The WHI estrogen plus progestin substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 strokes per 10,000 women-years) [see Clinical Studies, ( 14.3 )] . The increase in risk was demonstrated after the first year and persisted. 1 Immediately discontinue estrogen plus progestogen therapy if a stroke occurs or is suspected. Coronary Heart Disease The WHI estrogen-alone substudy reported no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies ( 14.3 )] . Subgroup analyses of women 50 to 59 years of age, who were less than 10 years since menopause, suggest a reduction (not statistically significant) of CHD events in those women receiving daily CE (0.625 mg)-alone compared to placebo (8 versus 16 per 10,000 women-years). 1 The WHI estrogen plus progestin substudy reported an increased risk (not statistically significant) of CHD events in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women years). 1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see Clinical Studies ( 14.3 )] . In postmenopausal women with documented heart disease (n = 2,763, average 66.7 years of age), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established CHD. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand, three hundred and twenty-one (2,321) women from the original HERS trial agreed to participate in an open-label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE plus MPA group and the placebo group in the HERS, HERS II, and overall. Venous Thromboembolism In the WHI estrogen-alone substudy, the risk of VTE (DVT and PE), was increased for women receiving daily CE (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women years). The increase in VTE risk was demonstrated during the first 2 years 3 [see Clinical Studies ( 14.3 )] . Immediately discontinue estrogen-alone therapy if a VTE occurs or is suspected. The WHI estrogen plus progestin substudy reported a statistically significant 2-fold greater rate of VTE in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was demonstrated during the first year and persisted 4 [see Clinical Studies ( 14.3 )] . Immediately discontinue estrogen plus progestogen therapy if a VTE occurs or is suspected. If feasible, discontinue estrogens at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
Side effects
The following serious adverse reactions are discussed elsewhere in labeling: Cardiovascular Disorders [see Boxed Warning , Warning and Precaution, ( 5.1 )] Malignant Neoplasms [see Boxed Warning , Warnings and Precautions ( 5.2 )] The most common adverse reactions (greater than or equal to 5 percent) with MINIVELLE are: headache, breast tenderness, back pain, pain in limb, nasopharyngitis, dyspepsia, nausea, sinusitis, and intermenstrual bleeding. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Noven at 1-800-455-8070 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. There were no clinical trials conducted with MINIVELLE. MINIVELLE is bioequivalent to Vivelle ® . The following adverse reactions are reported with Vivelle therapy: Table 1: Summary of Most Frequently Reported Adverse Reactions (Vivelle versus Placebo) Regardless of Relationship Reported at a Frequency ≥5 Percent † Represents milligrams of estradiol delivered daily by each system * NOS represents not otherwise specified ** NEC represents not elsewhere classified *** Application site erythema and application site irritation were observed in 3.2% or less of patients across treatment groups. Vivelle 0.025 mg/day † (N=47) N (%) Vivelle 0.0375 mg/day † (N=130) N (%) Vivelle 0.05 mg/day † (N=103) N (%) Vivelle 0.075 mg/day † (N=46) N (%) Vivelle 0.1 mg/day † (N=132) 2 N (%) Placebo (N=157) N (%) Gastrointestinal disorders Constipation 2 (4.3) 5 (3.8) 4 (3.9) 3 (6.5) 2 (1.5) 4 (2.5) Dyspepsia 4 (8.5) 12 (9.2) 3 (2.9) 2 (4.3) 0 10 (6.4) Nausea 2 (4.3) 8 (6.2) 4 (3.9) 0 7 (5.3) 5 (3.2) General disorders and administration site conditions *** Influenza-like illness 3 (6.4) 6 (4.6) 8 (7.8) 0 3 (2.3) 10 (6.4) Pain NOS* 0 8 (6.2) 0 2 (4.3) 7 (5.3) 7 (4.5) Infections and infestations Influenza 4 (8.5) 4 (3.1) 6 (5.8) 0 10 (7.6) 14 (8.9) Nasopharyngitis 3 (6.4) 16 (12.3) 10 (9.7) 9 (19.6) 11 (8.3) 24 (15.3) Sinusitis NOS* 4 (8.5) 17 (13.1) 13 (12.6) 3 (6.5) 7 (5.3) 16 (10.2) Upper respiratory tract infection NOS* 3 (6.4) 8 (6.2) 11 (10.7) 4 (8.7) 6 (4.5) 9 (5.7) Investigations Weight increased 4 (8.5) 5 (3.8) 2 (1.9) 2 (4.3) 0 3 (1.9) Musculoskeletal and connective tissue disorders Arthralgia 0 11 (8.5) 4 (3.9) 2 (4.3) 5 (3.8) 9 (5.7) Back pain 4 (8.5) 10 (7.7) 9 (8.7) 4 (8.7) 14 (10.6) 10 (6.4) Neck pain 3 (6.4) 4 (3.1) 4 (3.9) 0 6 (4.5) 2 (1.3) Pain in limb 0 10 (7.7) 7 (6.8) 2 (4.3) 6 (4.5) 9 (5.7) Nervous system disorders Headache NOS* 7 (14.9) 35 (26.9) 32 (31.1) 23 (50.0) 34 (25.8) 37 (23.6) Sinus headache 0 12 (9.2) 5 (4.9) 5 (10.9) 2 (1.5) 8 (5.1) Psychiatric disorders Anxiety NEC ** 3 (6.4) 5 (3.8) 0 0 2 (1.5) 4 (2.5) Depression 5 (10.6) 4 (3.1) 7 (6.8) 0 4 (3.0) 6 (3.8) Insomnia 3 (6.4) 6 (4.6) 4 (3.9) 2 (4.3) 2 (1.5) 9 (5.7) Reproductive system and breast disorders Breast tenderness 8 (17.0) 10 (7.7) 8 (7.8) 3 (6.5) 17 (12.9) 0 Dysmenorrhea 0 0 0 3 (6.5) 0 0 Intermenstrual bleeding 3 (6.4) 9 (6.9) 6 (5.8) 0 14 (10.6) 7 (4.5) Respiratory, thoracic and mediastinal disorders Sinus congestion 0 4 (3.1) 3 (2.9) 3 (6.5) 6 (4.5) 7 (4.5) Vascular disorders Hot flushes NOS* 3 (6.4) 0 3 (2.9) 0 0 6 (3.8) Hypertension NOS* 2 (4.3) 0 3 (2.9) 0 0 2 (1.3) During the clinical pharmacology studies with MINIVELLE, 35 percent or less of subjects experienced barely perceptible erythema. No transdermal systems were removed due to irritation. Three subjects (2.2 percent) reported mild discomfort while wearing MINIVELLE (N=136). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of MINIVELLE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Breast Breast enlargement Cardiovascular Palpitations, angina unstable Gastrointestinal Hemorrhage, diarrhea Skin Application site reactions, erythema, rash, hyperhidrosis, pruritis, urticaria Central Nervous System Dizziness, paresthesia, migraine, mood swings, emotional disorder, irritability, nervousness Miscellaneous Portal vein thrombosis, dyspnea, malaise, fatigue, peripheral edema, muscle spasms, paresthesia oral, swollen tongue, lip swelling, pharyngeal edema
Drug interactions
In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John’s wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions. Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. ( 7 )
Use in specific populations
8.1 Pregnancy Risk Summary MINIVELLE is not indicated for use in pregnancy. There are no data with the use of MINIVELLE in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 8.2 Lactation Risk Summary Estrogens are present in human milk and can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well established. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for MINIVELLE and any potential adverse effects on the breastfed child from MINIVELLE or from the underlying maternal condition. 8.4 Pediatric Use MINIVELLE is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population. 8.5 Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing MINIVELLE to determine whether those over 65 years of age differ from younger subjects in their response to MINIVELLE. The Women’s Health Initiative Studies In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies ( 14.3 )] . In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Warnings and Precautions ( 5.1 ), and Clinical Studies ( 14.3 )] . The Women’s Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.4 )] . Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.3 )] .
Pregnancy
8.1 Pregnancy Risk Summary MINIVELLE is not indicated for use in pregnancy. There are no data with the use of MINIVELLE in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Pediatric use
8.4 Pediatric Use MINIVELLE is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.
Geriatric use
8.5 Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing MINIVELLE to determine whether those over 65 years of age differ from younger subjects in their response to MINIVELLE. The Women’s Health Initiative Studies In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see Clinical Studies ( 14.3 )] . In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see Warnings and Precautions ( 5.1 ), and Clinical Studies ( 14.3 )] . The Women’s Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.4 )] . Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.3 )] .
Overdosage
Overdosage of estrogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of MINIVELLE therapy with institution of appropriate symptomatic care.
Description
(estradiol transdermal system) contains estradiol in a multipolymeric adhesive. The system is designed to release estradiol continuously upon application to intact skin. Five dosage strengths of MINIVELLE are available to provide nominal in vivo delivery rates of 0.025, 0.0375, 0.05, 0.075, or 0.1 mg of estradiol per day via the skin. Each corresponding system has an active surface area of 1.65, 2.48, 3.30, 4.95, or 6.6 cm 2 and contains 0.41, 0.62, 0.83, 1.24, or 1.65 mg of estradiol USP, respectively. The composition of the systems per unit area is identical. Estradiol USP is a white, crystalline powder, chemically described as estra-1,3,5 (10)-triene-3,17β-diol. The structural formula is The molecular formula of estradiol is C 18 H 24 0 2 . The molecular weight is 272.39 MINIVELLE is comprised of three layers. Proceeding from the visible surface toward the surface attached to the skin, these layers are (1) a polyolefin laminate backing (2) an adhesive formulation containing estradiol, acrylic adhesive, silicone adhesive, oleyl alcohol, NF, povidone, USP and dipropylene glycol, and (3) a polyester release liner which is attached to the adhesive surface and must be removed before the system can be used. The active component of the system is estradiol. The remaining components of the system are pharmacologically inactive. Estradiol USP Layers of MINIVELLE
Mechanism of action
12.1 Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism. Estrogens act to reduce the elevated concentrations of these hormones seen in postmenopausal women.
How supplied
16.1 How Supplied MINIVELLE (estradiol transdermal system), 0.025 mg per day - each 1.65 cm 2 system contains 0.41 mg of estradiol USP for nominal* delivery of 0.025 mg of estradiol per day. Patient Calendar Pack of 8 Systems…………………………………..NDC 68968-6625-8 MINIVELLE (estradiol transdermal system), 0.0375 mg per day - each 2.48 cm 2 system contains 0.62 mg of estradiol USP for nominal* delivery of 0.0375 mg of estradiol per day. Patient Calendar Pack of 8 Systems…………………………………..NDC 68968-6637-8 MINIVELLE (estradiol transdermal system), 0.05 mg per day - each 3.3 cm 2 system contains 0.83 mg of estradiol USP for nominal* delivery of 0.05 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………….NDC 68968-6650-8 MINIVELLE (estradiol transdermal system), 0.075 mg per day - each 4.95 cm 2 system contains 1.24 mg of estradiol USP for nominal* delivery of 0.075 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………….NDC 68968-6675-8 MINIVELLE (estradiol transdermal system), 0.1 mg per day - each 6.6 cm 2 system contains 1.65 mg of estradiol USP for nominal* delivery of 0.1 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………….NDC 68968-6610-8 *See Description 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [ see USP Controlled Room Temperature ] Do not store unpouched. Apply immediately upon removal from the protective pouch. Used transdermal systems still contain active hormone. To discard, fold the sticky side of the transdermal system together, place it in a sturdy child-proof container, and place this container in the trash. Used transdermal systems should not be flushed in the toilet.
Storage
16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [ see USP Controlled Room Temperature ] Do not store unpouched. Apply immediately upon removal from the protective pouch. Used transdermal systems still contain active hormone. To discard, fold the sticky side of the transdermal system together, place it in a sturdy child-proof container, and place this container in the trash. Used transdermal systems should not be flushed in the toilet.
Patient information
Advise women to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Vaginal Bleeding Inform postmenopausal women to report unusual vaginal bleeding to their healthcare providers as soon as possible [see Warnings and Precautions ( 5.2 )] Possible Serious Adverse Reactions with Estrogen–Alone Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen-alone therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warning and Precautions ( 5.1 , 5.2 , 5.3 )] . Possible Common Adverse Reactions with Estrogen–Alone Therapy Inform postmenopausal women of less serious but common adverse reactions of estrogen-alone therapy such as headache, breast pain and tenderness, nausea and vomiting.
Label text from the FDA structured product label by Noven Therapeutics, LLC (revised Jul 31, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Estradiol in 5 products
Minivelle NDC products (5)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 68968-6610 | Estradiol .1 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
| 68968-6625 | Estradiol .025 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
| 68968-6637 | Estradiol .0375 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
| 68968-6650 | Estradiol .05 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
| 68968-6675 | Estradiol .075 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
Minivelle recalls
- D-0336-2021 Apr 28, 2021 · Class II · Terminated
Defective Delivery System: Out of specification for release rate testing and shear, an attribute related to the adhesive properties of the transdermal patches. As a result, patients could experience patches that do not… - D-1207-2018 Oct 3, 2018 · Class II · Terminated
Defective Delivery System: out of specification results for shear, an attribute related to the adhesive properties of the transdermal patches. - D-1208-2018 Oct 3, 2018 · Class II · Terminated
Defective Delivery System: out of specification results for shear, an attribute related to the adhesive properties of the transdermal patches. - D-1209-2018 Oct 3, 2018 · Class II · Terminated
Defective Delivery System: out of specification results for shear, an attribute related to the adhesive properties of the transdermal patches. - D-1210-2018 Oct 3, 2018 · Class II · Terminated
Defective Delivery System: out of specification results for shear, an attribute related to the adhesive properties of the transdermal patches. - D-0862-2018 May 16, 2018 · Class II · Terminated
Defective Delivery System: no longer meets the specification for shear, an attribute related to the adhesive properties of the transdermal patches. As a result, patients could experience patches that do not stick well… - D-0863-2018 May 16, 2018 · Class II · Terminated
Defective Delivery System: no longer meets the specification for shear, an attribute related to the adhesive properties of the transdermal patches. As a result, patients could experience patches that do not stick well… - D-0923-2017 Jul 5, 2017 · Class III · Terminated
Defective Delivery System: Out of specification for peel force from the release liner specification during stability testing at 18M 25C/60%RH. - D-0485-2015 Apr 22, 2015 · Class II · Terminated
Temperature Abuse: Prolonged exposure to temperatures outside of labeled storage conditions.
Frequently asked questions
What is Minivelle used for?
1 INDICATIONS AND USAGE MINIVELLE is indicated for: MINIVELLE® is an estrogen indicated for: Treatment of moderate to severe vasomotor symptoms due to menopause ( 1.1 ) Prevention of postmenopausal osteoporosis ( 1.2 ) Limitations of Use When prescribing solely for the treatment of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for…
What are the side effects of Minivelle?
The following serious adverse reactions are discussed elsewhere in labeling: Cardiovascular Disorders [see Boxed Warning , Warning and Precaution, ( 5.1 )] Malignant Neoplasms [see Boxed Warning , Warnings and Precautions ( 5.2 )] The most common adverse reactions (greater than or equal to 5 percent) with MINIVELLE are: headache, breast tenderness, back pain, pain in limb, nasopharyngitis,… See the full label for the complete list.
Who makes Minivelle?
Minivelle is listed by 1 labeler in the FDA NDC directory, including Noven Therapeutics, LLC.
Has Minivelle been recalled?
The FDA enforcement database lists 9 recalls for Minivelle, most recently D-0336-2021 (class ii): Defective Delivery System: Out of specification for release rate testing and shear, an attribute related to the adhesive properties of the transdermal patches.…