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MENEST
Overview
What is MENEST?
Esterified estrogens is a mixture of the sodium salts of the sulfate esters of the estrogenic substances, principally estrone, that are of the type excreted by pregnant mares. It contains the concomitant component, 17α-estradiol. The content of total esterified estrogens is not less than 90 percent and not more than 110 percent of the labeled amount. Esterified estrogens contain not less than 75 percent and not more than 85 percent of sodium estrone sulfate, and not less than 6 percent and not more than 15 percent of sodium equilin sulfate, in such proportion that the total of these two components is not less than 90 percent, all percentages being calculated on the basis of the total esterified estrogens content.
Inactive Ingredients
0.3 mg Tablet:
0.625 mg Tablet
1.25 mg Tablet:
2.5 mg Tablet:
What does MENEST look like?
What are the available doses of MENEST?
Sorry No records found.
What should I talk to my health care provider before I take MENEST?
Sorry No records found
How should I use MENEST?
Menest is indicated in the:
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 and .) 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.
1. Given cyclically for short term use only:
For treatment of moderate to severe vasomotor symptoms, or moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause.
Administration should be cyclic (e.g., 3 weeks on and 1 week off).
What interacts with MENEST?
- Menest should not be used in women 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 a 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.
- Menest should not be used in patients with known hypersensitivity to its ingredients.
- Known or suspected pregnancy. There is no indication for Menest 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 .)
What are the warnings of MENEST?
Array
See.
The use of unopposed estrogens in women who have a uterus is associated with an increased risk of endometrial cancer.
1. Cardiovascular disorders
Estrogen and estrogen/progestin therapy has been associated with an increased risk of cardiovascular events such as myocardial infarction and stroke, as well as venous thrombosis and pulmonary embolism (venous thromboembolism or VTE). Should any of these occur or be suspected, estrogens should be discontinued immediately.
Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.
Array
In the Women's Health Initiative study (WHI), an increase in the number of myocardial infarctions and strokes has been observed in women receiving CE compared to placebo. These observations are preliminary. (See .)
In the CE/MPA substudy of WHI, an increased risk of coronary heart disease (CHD) events (defined as nonfatal myocardial infarction and CHD death) was observed in women receiving CE/MPA compared to women receiving placebo (37 vs 30 per 10,000 women-years). The increase in risk was observed in year one and persisted.
In the same substudy of WHI, an increased risk of stroke was observed in women receiving CE/MPA compared to women receiving placebo (29 vs 21 per 10,000 women-years). The increase in risk was observed after the first year and persisted.
In postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years) a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement study; HERS) treatment with CE/MPA (0.625mg/2.5mg per day) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE/MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE/MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred and twenty-one 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/MPA group and the placebo group in HERS, HERS II and overall.
Large doses of estrogen (5 mg conjugated estrogens per day), comparable to those used to treat cancer of the prostate and breast, have been shown in a large prospective clinical trial in men to increase the risks of nonfatal myocardial infarction, pulmonary embolism, and thrombophlebitis.
Array
In the Women's Health Initiative study (WHI), an increase in VTE has been observed in women receiving CE compared to placebo. These observations are preliminary. (See , .)
In the CE/MPA substudy of WHI, a 2-fold greater rate of VTE, including deep venous thrombosis and pulmonary embolism, was observed in women receiving CE/MPA compared to women receiving placebo. The rate of VTE was 34 per 10,000 women-years in the CE/MPA group compared to 16 per 10,000 women-years in the placebo group. The increase in VTE risk was observed during the first year and persisted.
If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
2. Malignant neoplasms
Array
The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12- fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than one year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for five to ten years or more and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued.
Clinical surveillance of all women taking estrogen/progestin combinations 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, of equivalent estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.
Array
The use of estrogens and progestins by postmenopausal women has been reported to increase the risk of breast cancer. The most important randomized clinical trial providing information about this issue is the Women's Health Initiative (WHI) substudy of CE/MPA (see ). The results from observational studies are generally consistent with those of the WHI clinical trial and report no significant variation in the risk of breast cancer among different estrogens or progestins, doses, or routes of administration.
The CE/MPA substudy of WHI reported an increased risk of breast cancer in women who took CE/MPA for a mean follow-up of 5.6 years. Observational studies have also reported an increased risk for estrogen/progestin combination therapy, and a smaller increased risk for estrogen alone therapy, after several years of use. In the WHI trial and from observational studies, the excess risk increased with duration of use. From observational studies, the risk appeared to return to baseline in about five years after stopping treatment. In addition, observational studies suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen/progestin combination therapy as compared to estrogen alone therapy.
In the CE/MPA substudy, 26% of the women reported prior use of estrogen alone and/or estrogen/progestin combination hormone therapy. After a mean follow-up of 5.6 years during the clinical trial, the overall relative risk of invasive breast cancer was 1.24 (95% confidence interval 1.01 – 1.54), and the overall absolute risk was 41 vs 33 cases per 10,000 women-years, for CE/MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 vs 25 cases per 10,000 women-years, for CE/MPA compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 vs 36 cases per 10,000 women-years for CE/MPA compared with placebo. In the same substudy, invasive breast cancers were larger and diagnosed at a more advanced stage in the CE/MPA group compared with the placebo group. Metastatic disease was rare with no apparent difference between the two groups. Other prognostic factors such as histologic subtype, grade and hormone receptor status did not differ between the groups.
The use of estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.
3. Dementia
In the Women's Health Initiative Memory Study (WHIMS), 4,532 generally healthy postmenopausal women 65 years of age and older were studied, of whom 35% were 70 to 74 years of age and 18% were 75 or older. After an average follow-up of 4 years, 40 women being treated with CE/MPA (1.8%, n = 2,229) and 21 women in the placebo group (0.9%, n = 2,303) received diagnoses of probable dementia. The relative risk for CE/MPA versus placebo was 2.05 (95% confidence interval 1.21 – 3.48), and was similar for women with and without histories of menopausal hormone use before WHIMS. The absolute risk of probable dementia for CE/MPA versus placebo was 45 versus 22 cases per 10,000 women-years, and the absolute excess risk for CE/MPA was 23 cases per 10,000 women-years.
It is unknown whether these findings apply to younger postmenopausal women. (See and .)
It is unknown whether these findings apply to estrogen alone therapy.
4. Gallbladder disease
A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
5. Hypercalcemia
Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level.
6. Visual abnormalities
Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued.
7. Hepatic adenoma
Benign hepatic adenomas appear to be associated with the use of oral contraceptives. Although benign, and rare, these may rupture and may cause death through intra-abdominal hemorrhage. Such lesions have not yet been reported in association with other estrogen or progestagen preparations but should be considered in estrogen users having abdominal pain and tenderness, abdominal mass, or hypovolemic shock. Hepatocellular carcinoma has also been reported in women taking estrogen-containing oral contraceptives. The relationship of this malignancy to these drugs is not known at this time.
What are the precautions of MENEST?
A. GENERAL
Array
Studies of the addition of progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer.
There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include a possible increased risk of breast cancer.
Array
In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogens on blood pressure was not seen. Blood pressure should be monitored at regular intervals with estrogen use.
Array
In patients with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications.
Array
Estrogens may be poorly metabolized in patients with impaired liver function. For patients with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised and in the case of recurrence, medication should be discontinued.
Array
Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Patients with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T and T serum concentrations in the normal range. Patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.
Array
Because estrogens may cause some degree of fluid retention, patients with conditions that might be influenced by this factor, such as a cardiac or renal dysfunction, warrant careful observation when estrogens are prescribed.
Array
Estrogens should be used with caution in individuals with severe hypocalcemia.
Array
The CE/MPA substudy of WHI reported that estrogen plus progestin increased the risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE/MPA versus placebo was 1.58 (95% confidence interval 0.77 – 3.24) but was not statistically significant. The absolute risk for CE/MPA versus placebo was 4.2 versus 2.7 cases per 10,000 women-years. In some epidemiologic studies, the use of estrogen alone, in particular for ten or more years, has been associated with an increased risk of ovarian cancer. Other epidemiologic studies have not found these associations.
Array
Endometriosis may be exacerbated with administration of estrogens. A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen alone therapy. For patients known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.
Array
Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.
B. PATIENT INFORMATION
Physicians are advised to discuss the leaflet with patients for whom they prescribe Menest.
C. LABORATORY TESTS
Estrogen administration should be initiated at the lowest dose approved for the indication and then guided by clinical response, rather than by serum hormone levels (e.g., estradiol, FSH).
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 antifactor 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) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T levels (by column or by radioimmunoassay) or T levels by radioimmunoassay. T resin uptake is decreased, reflecting the elevated TBG. Free T and free T 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 total 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 cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglycerides levels.
- Impaired glucose tolerance.
- Reduced response to metyrapone test.
E. CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY
Long-term continuous administration of estrogen, with and without progestin, in women with and without a uterus, has shown an increased risk of endometrial cancer, breast cancer, and ovarian cancer. (See and .)
Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.
F. PREGNANCY
Menest should not be used during pregnancy. (See .)
G. NURSING MOTHERS
Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving this drug. Caution should be exercised when Menest is administered to a nursing mother.
H. PEDIATRIC USE
Safety and effectiveness in pediatric patients have not been established.
I. GERIATRIC USE
In the Women's Health Initiative Memory Study, including 4,532 women 65 years of age and older, followed for an average of 4 years, 82% (n = 3,729) were 65 to 74 while 18% (n = 803) were 75 and over. Most women (80%) had no prior hormone therapy use. Women treated with conjugated estrogens plus medroxyprogesterone acetate were reported to have a two-fold increase in the risk of developing probable dementia. Alzheimer's disease was the most common classification of probable dementia in both the conjugated estrogens plus medroxyprogesterone acetate group and the placebo group. Ninety percent of the cases of probable dementia occurred in the 54% of women that were older than 70. (See .)
It is unknown whether these findings apply to estrogen alone therapy.
What are the side effects of MENEST?
See , and .
The following additional adverse reactions have been reported with estrogens and/or progestin therapy.
1. 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; premenstrual like syndrome, amenorrhea during and after treatment; cystitis like syndrome.
2. Breasts
Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.
3. Cardiovascular
Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.
4. Gastrointestinal
Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gall bladder disease; pancreatitis, enlargement of hepatic hemangiomas.
5. Skin
Chloasma or melasma, that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.
6. Eyes
Retinal vascular thrombosis; steepening of corneal curvature; intolerance to contact lenses.
7. Central nervous system
Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia.
8. Miscellaneous
Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.
What should I look out for while using MENEST?
Menest should not be used in women with any of the following conditions:
See.
The use of unopposed estrogens in women who have a uterus is associated with an increased risk of endometrial cancer.
What might happen if I take too much MENEST?
Serious ill effects have not been reported following acute ingestion of large doses of estrogen-containing drug products by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.
How should I store and handle MENEST?
Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010Tablets: 0.3 mg yellow, film-coated oblong tablet imprinted with M72 100's: 61570-072-01 0.625 mg orange, film-coated oblong tablet imprinted with M73 100's: 61570-073-01 1.25 mg green, film-coated oblong tablet imprinted with M74 100's: 61570-074-01 2.5 mg pink, film-coated oblong tablet imprinted with M75 50's: 61570-075-50Rx OnlyPrescribing Information as of September 2010
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
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.
Non-Clinical Toxicology
Menest should not be used in women with any of the following conditions:See.
The use of unopposed estrogens in women who have a uterus is associated with an increased risk of endometrial cancer.
Clinical experience has identified no interactions resulting from topical or systemic administration of other drugs concomitantly with acyclovir ointment 5%.
See , and .
The following additional adverse reactions have been reported with estrogens and/or progestin therapy.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
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