Get your patient on Estradiol - Estradiol tablet (Estradiol)
Estradiol - Estradiol tablet prescribing information
BOXED WARNING
ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER
Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of “natural” estrogens results in a different endometrial risk profile than “synthetic” estrogens at equivalent estrogen doses (See WARNINGS, Malignant neoplasms, Endometrial cancer ).
CARDIOVASCULAR AND OTHER RISKS
Estrogens with or without progestins should not be used for the prevention of cardiovascular disease (See WARNINGS, Cardiovascular disorders ).
The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo (See CLINICAL PHARMACOLOGY, Clinical Studies ).
The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy (See CLINICAL PHARMACOLOGY, Clinical Studies ).
Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
INDICATIONS AND USAGE
Estradiol tablets are indicated in the:
- Treatment of moderate to severe vasomotor symptoms associated with the menopause.
- Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
- Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.
- Treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease.
- Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only).
- Prevention of osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate (See CLINICAL PHARMACOLOGY, Clinical Studies ).
The mainstays for decreasing the risk of postmenopausal osteoporosis are weight bearing exercise, adequate calcium and vitamin D intake, and when indicated, pharmacologic therapy. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake. Vitamin D supplementation of 400 to 800 IU/day may also be required to ensure adequate daily intake in postmenopausal women.
DOSAGE AND ADMINISTRATION
When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin. Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary (see BOXED WARNINGS and WARNINGS ). For women who have a uterus, adequate diagnostic measures, such as endometrial sampling, when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding.
Patients should be started at the lowest dose for the indication.
1. For treatment of moderate to severe vasomotor symptoms, vulval and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible.
Attempts to discontinue or taper medication should be made at 3-month to 6-month intervals. The usual initial dosage range is 1 to 2 mg daily of estradiol adjusted as necessary to control presenting symptoms. The minimal effective dose for maintenance therapy should be determined by titration. Administration should be cyclic (e.g., 3 weeks on and 1 week off).
2. For treatment of female hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
Treatment is usually initiated with a dose of 1 to 2 mg daily of estradiol, adjusted as necessary to control presenting symptoms; the minimal effective dose for maintenance therapy should be determined by titration.
3. For treatment of breast cancer, for palliation only, in appropriately selected women and men with metastatic disease.
Suggested dosage is 10 mg three times daily for a period of at least three months.
4. For treatment of advanced androgen-dependent carcinoma of the prostate, for palliation only.
Suggested dosage is 1 to 2 mg three times daily. The effectiveness of therapy can be judged by phosphatase determinations as well as by symptomatic improvement of the patient.
5. For prevention of osteoporosis.
When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should be considered only for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate.
The lowest effective dose of estradiol has not been determined.
CONTRAINDICATIONS
Estrogens should not be used in individuals with any of the following conditions:
- Undiagnosed abnormal genital bleeding.
- Known, suspected or history of cancer of the breast except in appropriately selected patients being treated for metastatic disease.
- Known or suspected estrogen-dependent neoplasia.
- Active deep vein thrombosis, pulmonary embolism or history of these conditions.
- Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction).
- Liver dysfunction or disease.
- Estradiol tablets should not be used in patients with known hypersensitivity to its ingredients.
- Known or suspected pregnancy. There is no indication for estradiol tablets in pregnancy. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins from oral contraceptives inadvertently during early pregnancy (See PRECAUTIONS ).
ADVERSE REACTIONS
See BOXED WARNINGS , WARNINGS , and PRECAUTIONS .
The following additional adverse reactions have been reported with estrogen and/or progestin therapy.
Genitourinary system
Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting, dysmenorrhea
Increase in size of uterine leiomyomata
Vaginitis, including vaginal candidiasis
Change in amount of cervical secretion
Changes in cervical ectropion
Ovarian cancer; endometrial hyperplasia; endometrial cancer
Breasts
Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer
Cardiovascular
Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure
Gastrointestinal
Nausea, vomiting
Abdominal cramps, bloating
Cholestatic jaundice
Increased incidence of gallbladder disease
Pancreatitis
Enlargement of hepatic hemangiomas
Skin
Chloasma or melasma that may persist when drug is discontinued
Erythema multiforme
Erythema nodosum
Hemorrhagic eruption
Loss of scalp hair
Hirsutism
Pruritus, rash
Eyes
Retinal vascular thrombosis
Steepening of corneal curvature
Intolerance to contact lenses
Central Nervous System
Headache, migraine, dizziness
Mental depression
Chorea
Nervousness, mood disturbances, irritability
Exacerbation of epilepsy
Dementia
Miscellaneous
Increase or decrease in weight
Reduced carbohydrate tolerance
Aggravation of porphyria
Edema
Arthralgias; leg cramps
Changes in libido
Urticaria
Angioedema
Anaphylactoid/anaphylactic reactions
Hypocalcemia
Exacerbation of asthma
Increased triglycerides
To report SUSPECTED ADVERSE REACTIONS, contact Blu Pharmaceuticals at 1-877-264-0258 or the FDA at 1-800-FDA-1088 or www.fda.gov/ medwatch .
D. Drug/Laboratory Test Interactions
- Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.
- Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T 4 levels (by column or by radioimmunoassay) or T 3 levels by radioimmunoassay. T 3 resin uptake is decreased, reflecting the elevated TBG. Free T 4 and free T 3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.
- Other binding proteins may be elevated in serum, i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased circulating corticosteroids and sex steroids, respectively. Free hormone concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
- Increased plasma HDL and HDL 2 subfraction concentrations, reduced LDL cholesterol concentration, increased triglycerides levels.
- Impaired glucose tolerance.
- Reduced response to metyrapone test.
DESCRIPTION
Estradiol tablets, USP for oral administration contains 0.5, 1 or 2 mg of micronized estradiol, USP per tablet.
Estradiol, USP (17β-estradiol) is a white, crystalline solid, chemically described as estra-1,3,5,(10)-triene-3, 17β-diol. The structural formula is:
In addition, each tablet for oral administration contains the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium starch glycolate.
CLINICAL PHARMACOLOGY
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 by 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 levels of these hormones seen in postmenopausal women.
Pharmacokinetics
Distribution
The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin.
Metabolism
Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.
Excretion
Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates.
Special Populations
No pharmacokinetic studies were conducted in special populations, including patients with renal or hepatic impairment.
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 preparations (Hypericum perforatum), 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 side effects.
Clinical Studies
Osteoporosis
Most prospective studies of efficacy for this indication have been carried out in white menopausal women, without stratification by other risk factors, and tend to show a universally salutary effect on bone.
The results of a two-year, randomized, placebo-controlled, double-blind, dose-ranging study have shown that treatment with 0.5 mg estradiol daily for 23 days (of a 28 day cycle) prevents vertebral bone mass loss in postmenopausal women. When estrogen therapy is discontinued, bone mass declines at a rate comparable to the immediate postmenopausal period. There is no evidence that estrogen replacement therapy restores bone mass to premenopausal levels.
Women’s Health Initiative Studies
The Women’s Health Initiative (WHI) enrolled a total of 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral 0.625 mg conjugated estrogens (CE) per day alone or the use of oral 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate (MPA) per day compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome studied. A “global index” included the earliest occurrence of CHD, invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, or death due to other cause. The study did not evaluate the effects of CE or CE/MPA on menopausal symptoms.
The CE/MPA substudy was stopped early because, according to the predefined stopping rule, the increased risk of breast cancer and cardiovascular events exceeded the specified benefits included in the “global index.” Results of the CE/MPA substudy, which included 16,608 women (average age of 63 years, range 50 to 79; 83.9% White, 6.5% Black, 5.5% Hispanic), after an average follow-up of 5.2 years are presented in Table 1 below:
Table 1: RELATIVE AND ABSOLUTE RISK SEEN IN THE CE/MPA SUBSTUDY OF WHI 1
Event 2 | Relative Risk CE/MPA vs placebo at 5.2 Years (95% CI 3 ) | Placebo n = 8102 | CE/MPA n = 8506 |
Absolute Risk per 10,000 Women-Years | |||
CHD events Non-fatal MI CHD death | 1.29 (1.02 to 1.63) 1.32 (1.02 to 1.72) 1.18 (0.70 to 1.97) | 30 23 6 | 37 30 7 |
Invasive breast cancer 4 | 1.26 (1 to 1.59) | 30 | 38 |
Stroke | 1.41 (1.07 to 1.85) | 21 | 29 |
Pulmonary embolism | 2.13 (1.39 to 3.25) | 8 | 16 |
Colorectal cancer | 0.63 (0.43 to 0.92) | 16 | 10 |
Endometrial cancer | 0.83 (0.47 to 1.47) | 6 | 5 |
Hip fracture | 0.66 (0.45 to 0.98) | 15 | 10 |
Death due to causes other than the events above | 0.92 (0.74 to 1.14) | 40 | 37 |
Global Index 2 | 1.15 (1.03 to 1.28) | 151 | 170 |
Deep vein thrombosis 5 | 2.07 (1.49 to 2.87) | 13 | 26 |
Vertebral fractures 5 | 0.66 (0.44 to 0.98) | 15 | 9 |
Other osteoporotic fractures 5 | 0.77 (0.69 to 0.86) | 170 | 131 |
1 adapted from JAMA, 2002; 288:321-333
2 a subset of the events was combined in a “global index”, defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes
3 nominal confidence intervals unadjusted for multiple looks and multiple comparisons
4 includes metastatic and non-metastatic breast cancer with the exception of in situ breast cancer
5 not included in Global Index
For those outcomes included in the “global index,” the absolute excess risks per 10,000 women-years in the group treated with CE/MPA were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while the absolute risk reductions per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the “global index” was 19 per 10,000 women-years. There was no difference between the groups in terms of all-cause mortality (See BOXED WARNINGS , WARNINGS , and PRECAUTION S).
Women’s Health Initiative Memory Study
The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47% were age 65 to 69 years, 35% were 70 to 74 years, and 18% were 75 years of age and older) to evaluate the effects of CE/MPA (0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate) on the incidence of probable dementia (primary outcome) compared with placebo.
After an average follow-up of 4 years, 40 women in the estrogen/progestin group (45 per 10,000 women-years) and 21 in the placebo group (22 per 10,000 women-years) were diagnosed with probable dementia. The relative risk of probable dementia in the hormone therapy group was 2.05 (95% CI, 1.21 to 3.48) compared to placebo. Differences between groups became apparent in the first year of treatment. It is unknown whether these findings apply to younger postmenopausal women (See BOXED WARNING and WARNINGS, Dementia ).
Clinical Studies
Osteoporosis
Most prospective studies of efficacy for this indication have been carried out in white menopausal women, without stratification by other risk factors, and tend to show a universally salutary effect on bone.
The results of a two-year, randomized, placebo-controlled, double-blind, dose-ranging study have shown that treatment with 0.5 mg estradiol daily for 23 days (of a 28 day cycle) prevents vertebral bone mass loss in postmenopausal women. When estrogen therapy is discontinued, bone mass declines at a rate comparable to the immediate postmenopausal period. There is no evidence that estrogen replacement therapy restores bone mass to premenopausal levels.
Women’s Health Initiative Studies
The Women’s Health Initiative (WHI) enrolled a total of 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral 0.625 mg conjugated estrogens (CE) per day alone or the use of oral 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate (MPA) per day compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome studied. A “global index” included the earliest occurrence of CHD, invasive breast cancer, stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, or death due to other cause. The study did not evaluate the effects of CE or CE/MPA on menopausal symptoms.
The CE/MPA substudy was stopped early because, according to the predefined stopping rule, the increased risk of breast cancer and cardiovascular events exceeded the specified benefits included in the “global index.” Results of the CE/MPA substudy, which included 16,608 women (average age of 63 years, range 50 to 79; 83.9% White, 6.5% Black, 5.5% Hispanic), after an average follow-up of 5.2 years are presented in Table 1 below:
Table 1: RELATIVE AND ABSOLUTE RISK SEEN IN THE CE/MPA SUBSTUDY OF WHI 1
Event 2 | Relative Risk CE/MPA vs placebo at 5.2 Years (95% CI 3 ) | Placebo n = 8102 | CE/MPA n = 8506 |
Absolute Risk per 10,000 Women-Years | |||
CHD events Non-fatal MI CHD death | 1.29 (1.02 to 1.63) 1.32 (1.02 to 1.72) 1.18 (0.70 to 1.97) | 30 23 6 | 37 30 7 |
Invasive breast cancer 4 | 1.26 (1 to 1.59) | 30 | 38 |
Stroke | 1.41 (1.07 to 1.85) | 21 | 29 |
Pulmonary embolism | 2.13 (1.39 to 3.25) | 8 | 16 |
Colorectal cancer | 0.63 (0.43 to 0.92) | 16 | 10 |
Endometrial cancer | 0.83 (0.47 to 1.47) | 6 | 5 |
Hip fracture | 0.66 (0.45 to 0.98) | 15 | 10 |
Death due to causes other than the events above | 0.92 (0.74 to 1.14) | 40 | 37 |
Global Index 2 | 1.15 (1.03 to 1.28) | 151 | 170 |
Deep vein thrombosis 5 | 2.07 (1.49 to 2.87) | 13 | 26 |
Vertebral fractures 5 | 0.66 (0.44 to 0.98) | 15 | 9 |
Other osteoporotic fractures 5 | 0.77 (0.69 to 0.86) | 170 | 131 |
1 adapted from JAMA, 2002; 288:321-333
2 a subset of the events was combined in a “global index”, defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes
3 nominal confidence intervals unadjusted for multiple looks and multiple comparisons
4 includes metastatic and non-metastatic breast cancer with the exception of in situ breast cancer
5 not included in Global Index
For those outcomes included in the “global index,” the absolute excess risks per 10,000 women-years in the group treated with CE/MPA were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while the absolute risk reductions per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the “global index” was 19 per 10,000 women-years. There was no difference between the groups in terms of all-cause mortality (See BOXED WARNINGS , WARNINGS , and PRECAUTION S).
Women’s Health Initiative Memory Study
The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47% were age 65 to 69 years, 35% were 70 to 74 years, and 18% were 75 years of age and older) to evaluate the effects of CE/MPA (0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate) on the incidence of probable dementia (primary outcome) compared with placebo.
After an average follow-up of 4 years, 40 women in the estrogen/progestin group (45 per 10,000 women-years) and 21 in the placebo group (22 per 10,000 women-years) were diagnosed with probable dementia. The relative risk of probable dementia in the hormone therapy group was 2.05 (95% CI, 1.21 to 3.48) compared to placebo. Differences between groups became apparent in the first year of treatment. It is unknown whether these findings apply to younger postmenopausal women (See BOXED WARNING and WARNINGS, Dementia ).
HOW SUPPLIED
Estradiol Tablets, USP, 0.5 mg are white to off-white, round, convex, bisected tablets, debossed “ Є ” above the bisect and “87” below the bisect on one side, and plain on the other side.
NDC 24658-702-01 in bottles of 100
NDC 24658-702-05 in bottles of 500
Estradiol Tablets, USP, 1 mg are white to off-white, round, convex, bisected tablets, debossed “ Є ” above the bisect and “88” below the bisect on one side and plain on the other side.
NDC 24658-703-01 in bottles of 100
NDC 24658-703-05 in bottles of 500
Estradiol Tablets, USP, 2 mg are white to off-white, round, convex, bisected tablets, debossed “ Є ” above the bisect and “89” below the bisect on one side and plain on the other side.
NDC 24658-704-90 in bottles of 90
NDC 24658-704-01 in bottles of 100
NDC 24658-704-05 in bottles of 500
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense contents in a tight, light-resistant container as defined in the USP, with a child-resistant closure, as required.
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
Distributed by:
PuraCap Laboratories, LLC
DBA Blu Pharmaceuticals
Greenvale, NY 11548
Manufactured in USA
Rev. 05-2024-00
MF087REV05/24B
ZLN001
