Minivelle
Name: Minivelle
How supplied
Dosage Forms And Strengths
Transdermal system 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day, and 0.1 mg/day.
MINIVELLE (estradiol transdermal system), 0.0375 mg per day - each 2.48 cm² system contains 0.62mg of estradiol USP for nominal* delivery of 0.0375 mg of estradiol per day.
Patient Calendar Pack of 8 Systemsâ¦â¦â¦â¦â¦â¦â¦..NDC 68968-6637-8
Carton of 3 Patient Calendar Packs of 8 Systemsâ¦â¦.NDC 68968-6637-3
MINIVELLE (estradiol transdermal system), 0.05 mg per day - each 3.3 cm² system contains 0.83 mg of estradiol USP for nominal* delivery of 0.05 mg of estradiol per day.
Patient Calendar Pack of 8 Systemsâ¦â¦â¦â¦â¦â¦â¦.NDC 68968-6650-x
Carton of 3 Patient Calendar Packs of 8 Systemsâ¦â¦NDC 68968-6650-x
MINIVELLE (estradiol transdermal system), 0.075 mg per day - each 4.95 cm² system contains 1.24 mg of estradiol USP for nominal* delivery of 0.075 mg of estradiol per day.
Patient Calendar Pack of 8 Systemsâ¦â¦â¦â¦â¦â¦â¦.NDC 68968-6675-8
Carton of 3 Patient Calendar Packs of 8 Systemsâ¦â¦NDC 68968-6675-3
MINIVELLE (estradiol transdermal system), 0.1 mg per day - each 6.6 cm² system contains 1.65mg of estradiol USP for nominal* delivery of 0.1 mg of estradiol per day.
Patient Calendar Pack of 8 Systemsâ¦â¦â¦â¦â¦â¦â¦.NDC 68968-6610-8
Carton of 3 Patient Calendar Packs of 8 Systemsâ¦â¦NDC 68968-6610-3
* See DESCRIPTION
Storage and Handling
Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
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.
Manufactured by: Noven Pharmaceuticals Inc., Miami, FL 33186. Approved 10/2012
Overdose
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.
What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.
What should I avoid while using Minivelle (estradiol transdermal)?
Grapefruit and grapefruit juice may interact with estradiol and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.
What other drugs will affect Minivelle (estradiol transdermal)?
Other drugs may interact with estradiol, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.
Contraindications
Minivelle is contraindicated in women with any of the following conditions:
- Undiagnosed abnormal genital bleeding
- Known, suspected or history of breast cancer
- Known or suspected estrogen-dependent neoplasia
- Active DVT, PE, or a history of these conditions
- Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
- Known anaphylactic reaction or angioedema or hypersensitivity with Minivelle
- Known liver impairment or disease
- Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
- Known or suspected pregnancy
Adverse Reactions
The following serious adverse reactions are discussed elsewhere in labeling:
- Cardiovascular Disorders [see Boxed Warning, Warning and Precaution, (5.1)]
- Endometrial Cancer [see Boxed Warning, Warnings and Precautions (5.2)]
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:
| † 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).
Postmarketing Experience
The following additional 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
Use in specific populations
Pregnancy
Minivelle should not be used during pregnancy [see Contraindications (4)]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy.
Nursing Mothers
Minivelle should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogen therapy. Caution should be exercised when Minivelle is administered to a nursing woman.
Pediatric Use
Minivelle is not indicated in children. Clinical studies have not been conducted in the pediatric population.
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 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 women⁸ [see Warnings and Precautions (5.3), and Clinical Studies (14.3)].
Renal Impairment
The effect of renal impairment on the pharmacokinetics of Minivelle has not been studied.
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of Minivelle has not been studied.
Minivelle Description
Minivelle (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 cm2 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 C18H2402. 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 polyester film laminate (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.
How Supplied/Storage and Handling
How Supplied
Minivelle (estradiol transdermal system), 0.025 mg per day - each 1.65 cm2 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 cm2 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 cm2 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 cm2 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 cm2 system contains 1.65mg 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
Storage and Handling
Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
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.