DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,022,053 B2 Mueller Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,022,053 B2 Mueller Et Al US008022053B2 (12) United States Patent (10) Patent No.: US 8,022,053 B2 Mueller et al. (45) Date of Patent: Sep. 20, 2011 (54) ORAL SOLID DOSAGE FORMS CONTAINING 4,755,386 A 7, 1988 Hsiao et al. A LOW DOSE OF ESTRADIOL 5,073,374. A 12/1991 McCarty 5,776.492. A 7/1998 Betzing et al. 5,891,867 A * 4/1999 Lanquetin et al. ............ 514,170 (75) Inventors: Kristina Mueller, Berlin (DE); Torsten 5,891,868 A 4/1999 Cummings et al. Wagner, Berlin (DE); Adrian Funke, 6,030,988 A 2/2000 Gilis et al. Berlin (DE); Christian Zurth, Berlin 6,060,077 A * 5/2000 Meignant ...................... 424/434 (DE) 6,323,366 B1 1 1/2001 Wolfe et al. 6,326,366 B1* 12/2001 Potter et al. ................... 514, 182 6,455,069 B1 9, 2002 Michaud et al. (73) Assignee: Bayer Schering Pharma 6,521,253 B1 2/2003 Forsman et al. Aktiengesellschaft, Berlin (DE) 6,558,707 B1 5/2003 Thosar et al. 6,653,298 B2 * 1 1/2003 Potter et al. ................... 514, 182 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (Continued) U.S.C. 154(b) by 1017 days. FOREIGN PATENT DOCUMENTS (21) Appl. No.: 11/262,952 EP 04.078O140 11, 2004 (Continued) (22) Filed: Nov. 1, 2005 OTHER PUBLICATIONS (65) Prior Publication Data The Contraception Report, “Bioecuivalence between Brand-Name US 2006/O 111334 A1 May 25, 2006 and Generic OCs.” Jun. 2002, 13(2), 6-8.* Related U.S. Application Data (Continued) (60) Provisional application No. 60/623,858, filed on Nov. Primary Examiner — San-Ming Hui 2, 2004. Assistant Examiner — Paul Zarek (30) Foreign Application Priority Data (74) Attorney, Agent, or Firm — Millen, White, Zelano & Branigan, P.C. Nov. 2, 2004 (EP) ..................................... O4O78O14 (57) ABSTRACT (51) Int. Cl. A6 IK3I/56 (2006.01) The present invention relates to oral Solid dosage forms con (52) U.S. Cl. ....................................................... S14f182 taining a very low dose of estradiol. The dosage forms are (58) Field of Classification Search ................... 514f182 formulated in a manner so as to avoid degradation of the See application file for complete search history. estradiol and to minimise the content of polyvinylpyrroli done, while still achieving similar fast dissolution of the (56) References Cited estradiol. The dosage forms are useful in preventing or treat ing a physical condition in a woman caused by insufficient U.S. PATENT DOCUMENTS endogenous levels of estradiol. 2,096,744 A 10, 1937 Hildebrandt et al. 3,318,925 A 5, 1967 Anner et al. 25 Claims, 1 Drawing Sheet Conc. pg/mL) 10 O 1 2 3 4 5 6 8 10 12 14 24 36 48 Time (hour US 8,022,053 B2 Page 2 U.S. PATENT DOCUMENTS Chaumeil JC, “Micronization: A Method of Improving the Bioavail 6,716,453 B1 4/2004 Harden et al. ability of Poorly Soluble Drugs.” Methods and Findings in Experi 6,962.908 B2 11/2005 Aloba et al. mental and Clinical Pharmacology, 1998, 20(3), 211-215.* 6,987,101 B1 1/2006 Nashed Vagifem (R) product information sheet, Jul. 2003.* 2002/0173487 A1* 11/2002 Backenfeld et al. ............ 514/58 Moneghini, et al.: “Studies in Dissolution Enhancement of Atenolol. 2003. O104058 A1* 6, 2003 Rudnic et al. 424/468 Part I.” International Journal of Pharmceutics 175; 1998; pp. 177 2003. O144258 A1* 7, 2003 Hei1 et al. ... 514f1 70 183. 2003,019 1103 A1* 10, 2003 Grubb et al. 514, 182 Voigt, et al., “Granulometrische Erfassung Des Einflusses Von 2005/0020554 A1 1/2005 Ahmed et al. ................ 514, 182 Polyvinylpyrrollidon Auf Die LoeSungsgeschwindigkeit FOREIGN PATENT DOCUMENTS Schwerloeslicher Arzneistoffe.” Wissenschaftsbereich Pharmazie FR 2823976 A 10, 2002 35; 1980; pp. 311-312. RU 2101013 C1 11F1996 “Novel Hormone Composition and Use Thereof. Summary of FR WO WO97, 12600 A1 4f1997 2823796. WO WO98,04268 * 2/1998 Loyola University Health System Article: Drospirenone/Ethinyl WO WO 98.27929 7, 1998 WO WO99,26631 A1 6, 1999 Estradiol (Oral) (Tablet); 2005. WO WOO1, 52857 A1 T 2001 NCBI Article: The Effect of a Novel Vaginal Ring Delivering WO WO O2/47632 A1 6, 2002 Oestradiol Acetate on Climacteric Symptoms in Postmenopausal WO WO O2/49675 A1 6, 2002 Women. Buckler H. Al-AZZawi F; UKVR Multicentre Trial Group. WO WOO3,055495 T 2003 Department of Endocrinology, University of Manchester and Hope OTHER PUBLICATIONS Hospital, Stott Lane, Salford M68HD, UK, 2003. BJOG Article: An International Journal of Obstetrics & Gynaecology Karalis V. Macheras P. Van Peer A, and Shah VP, “Bioavailability and vol. 110 p. 753–Aug. 2003 doi10.1111?. 1471-0528.2003.02408.x bioecuivalence: focus on physiological factors and variability.” Phar vol. 110 Issue 8. maceutical Research, Aug. 2008 (Epub Jun. 2008), 25(8), 1956 Estradiol Article: What is the most important information I should 1962.* know about estradiol?, 2006. Timmer CJ and Geurts TB, “Bioeduivalence assessment of three Article: MedicineNet.com article: Estradiol/ethinyl Estradiol-Oral, different estradiol formulations in postmenopausal women in an 2005. open, randomized, single-dose, 3-way cross-over study.” European Article: Drug Digest, 2005. Journal of Drug Metabolism and Pharmacokinetics, Jan. 3, 1999, 24(1), 47-53.* * cited by examiner U.S. Patent Sep. 20, 2011 US 8,022,053 B2 ConC. pg/mL) 10 O 0 1 2 3 4 5 6 8 10 12 14 24, 36 48 Time (hour Fig. 1 US 8,022,053 B2 1. 2 ORAL SOLID DOSAGE FORMS CONTAINING Successfully determined by performing linear extrapolation A LOW DOSE OF ESTRADIOL of known serum levels resulting from daily oral administra tion of 1-3 mg estradiol. This application claims the benefit of the filing date of U.S. When formulating a solid oral dosage form intended for Provisional Application Ser. No. 60/623,858 filed Nov. 2, 5 immediate release of a low dose of a highly hydrophobic 2004. active ingredient, such as estradiol, the person skilled in phar maceutical Science would consideri) increasing the disinte FIELD OF INVENTION gration of the oral dosage form into Smaller fragments, ii) increasing the release of the active ingredient into the gastric The present invention relates to pharmaceutical composi fluid, and iii) increasing the dissolution rate of the active tions, in particular oral Solid dosage forms, comprising a low ingredient in the gastric fluid so as to prevent that the active dose estradiol. The dosage forms of the present invention ingredient enters the lower intestinal tract before being allow for good chemical stability of the estradiol during stor absorbed in the upper intestinal tract, which is the primary site age while still achieving a high dissolution rate of the estra of absorption for large molecules. diol- in0 water. 15 In order to do so, the person skilled in pharmaceutical Science would, as his primary option, choose to formulate the BACKGROUND OF THE INVENTION Solid dosage form using micronised material of the active ingredient to provide a high Surface area. The high Surface Pharmaceutical dosage forms containing naturally or syn area will then allow for a rapid dissolution. thetically derived steroidal hormones often contain a low As a second option, the scientist would formulate the solid dose of these active ingredients. In the present invention the dosage form using excipients promoting disintegration in dose of estradiol is significantly lower than what has so far combination with excipients promoting the wetting/solubilis been administered orally in the treatment of physical condi ing of the active ingredient in water or in gastric fluid. Nor tions associated with insufficient endogenous levels of estro- 25 mally, the scientist would select polyvinylpyrrolidone (PVP), gens in Women. which is an excipient exhibiting solubilising effect (improv According to U.S. Pat. No. 5,891,868 (Cummings et al.), ing the wettability), but also binding capacity making this the risk of bone fractures in postmenopausal women was excipient a “first choice” option, in particularly, when formu reduced by administering transdermally about 20 ug of estra lating oral Solid dosage forms of highly hydrophobic drugs. diol, or even less than about 20 g of estradiol, per day. 30 The solubilising effect of polyvinylpyrrolidone is well Transdermal administration resulted in effective serum levels described in the literature. For example, polyvinylpyrroli in the range between 5 and 20 pg/ml, which remained within done has been shown to improve the solubility and dissolu that range for an extended period of time. Cummings et al. tion rate of atenolol (Moneghini et al. IntJ Pharm 175; 1998: also suggested to administer the exogenous estrogen by other 177-183) and to increase the dissolution of prednisolone, Suitable routes, for example by oral or parenteral administra 35 nitrofurantoine and nitrofural considerably from gels con tion, but Cummings et al. further stated that “the estrogen taining 1-10% w/w of polyvinylpyrrolidone (Voigt etal. Phar should be administered parenterally or transdermally rather mazie 35; 1980:311-312). than orally. The former routes of administration are preferred WO 01/52857 describes manufacturing of oral dosage over oral administration because oral administration of estro forms containing 1 to 3 mg of estradiol with polyvinylpyr 40 rollidone 25000. gen may lead to increased levels of sex hormone binding However, the present inventors have found that when a globulin. Sex hormone binding globulin may diminish the lower dose of estradiol is applied in a tablet formulation beneficial effects of administering estrogen to postmeno similar to those described in example 1 of WO 01/52857, a pausal Subjects, particularly Subjects exhibiting signs of significant loss of estradiol during storage is detected, i.e. the osteoporosis or loss of bone mineral density'.
Load more

Recommended publications
  • Depo-Estradiol (Estradiol Cypionate) Injection
    Market Applicability Market DC GA KY MD NJ NY WA Applicable X X X X X X NA Depo-Estradiol (estradiol cypionate) injection Override(s) Approval Duration Prior Authorization 1 year Medications Depo-Estradiol (estradiol cypionate) injection APPROVAL CRITERIA Requests for Depo-Estradiol (estradiol cypionate) injection may be approved when the following criteria are met: I. Individual is using to treat moderate to severe vasomotor symptoms associated with menopause; OR II. Individual has been diagnosed with hypoestrogenism due to hypogonadism; OR III. Individual has a diagnosis of gender dysphoria or gender identity disorder (WPATH 2012, Endocrine Society 2017) ; AND IV. Individual is 16 years of age or older; AND V. The goal of treatment is male-to-female gender reassignment. Requests for Depo-Estradiol (estradiol cypionate) injection may not be approved for any of the following: I. Individual has undiagnosed abnormal genital bleeding; OR II. Individual has known or suspected cancer of the breast; OR III. Individual has known or suspected estrogen-dependent neoplasia; OR IV. Individual has active deep vein thrombosis, pulmonary embolism or history of these conditions; OR V. Individual has active or recent (within the past year) arterial thromboembolic disease (such as stroke or myocardial infarction); OR VI. Individual has liver dysfunction or disease. PAGE 1 of 2 02/24/2020 New Program Date 02/24/2020 CRX-ALL-0519-20 This policy does not apply to health plans or member categories that do not have pharmacy benefits, nor does it apply to Medicare. Note that market specific restrictions or transition-of-care benefit limitations may apply.
    [Show full text]
  • Pms-ESTRADIOL VALERATE INJECTION
    PRODUCT MONOGRAPH Prpms-ESTRADIOL VALERATE INJECTION Estradiol Valerate 10 mg/mL Estrogen PHARMASCIENCE INC. Date of Revision: 6111 Royalmount Avenue, Suite 100 June 30, 2009 Montreal, Quebec H4P 2T4 Control Number: 120632 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION……………………………...3 SUMMARY PRODUCT INFORMATION……………………………………….3 INDICATIONS AND CLINICAL USE…………………………………………...3 CONTRAINDICATIONS…………………………………………………………4 WARNINGS AND PRECAUTIONS…………………………………….……….5 ADVERSE REACTIONS………………………………………………………...13 DRUG INTERACTIONS………………………………………………………...15 DOSAGE AND ADMINISTRATION…………………………………………...17 OVERDOSAGE………………………………………………………………….19 ACTION AND CLINICAL PHARMACOLOGY……………………………….19 STORAGE AND STABILITY…………………………………………………...22 DOSAGE FORMS, COMPOSITION AND PACKAGING……………………..22 PART II: SCIENTIFIC INFORMATION…………………………………………….23 PHARMACEUTICAL INFORMATION………………………………………...23 CLINICAL TRIALS……………………………………………………………...24 DETAILED PHARMACOLOGY………………………………………………..24 REFERENCES…………………………………………………………………...25 PART III: CONSUMER INFORMATION……………………………………………………27 2 PRODUCT MONOGRAPH Prpms- ESTRADIOL VALERATE INJECTION (Estradiol Valerate) 10 mg/mL PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY PRODUCT INFORMATION Route of Dosage Form / Strength Clinically Relevant Nonmedicinal Administration Ingredients Intramuscular Injection / 10 mg/mL Sesame Oil For a complete listing see Dosage Forms, Composition and Packaging section. INDICATIONS AND CLINICAL USE pms-ESTRADIOL VALERATE INJECTION is indicated in the treatment of: I. amenorrhea (primary
    [Show full text]
  • Estradiol-17Β Pharmacokinetics and Histological Assessment Of
    animals Article Estradiol-17β Pharmacokinetics and Histological Assessment of the Ovaries and Uterine Horns following Intramuscular Administration of Estradiol Cypionate in Feral Cats Timothy H. Hyndman 1,* , Kelly L. Algar 1, Andrew P. Woodward 2, Flaminia Coiacetto 1 , Jordan O. Hampton 1,2 , Donald Nickels 3, Neil Hamilton 4, Anne Barnes 1 and David Algar 4 1 School of Veterinary Medicine, Murdoch University, Murdoch 6150, Australia; [email protected] (K.L.A.); [email protected] (F.C.); [email protected] (J.O.H.); [email protected] (A.B.) 2 Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne 3030, Australia; [email protected] 3 Lancelin Veterinary Hospital, Lancelin 6044, Australia; [email protected] 4 Department of Biodiversity, Conservation and Attractions, Locked Bag 104, Bentley Delivery Centre 6983, Australia; [email protected] (N.H.); [email protected] (D.A.) * Correspondence: [email protected] Received: 7 September 2020; Accepted: 17 September 2020; Published: 21 September 2020 Simple Summary: Feral cats (Felis catus) have a devastating impact on Australian native fauna. Several programs exist to control their numbers through lethal removal, using tools such as baiting with toxins. Adult male cats are especially difficult to control. We hypothesized that one way to capture these male cats is to lure them using female cats. As female cats are seasonal breeders, a method is needed to artificially induce reproductive (estrous) behavior so that they could be used for this purpose year-round (i.e., regardless of season).
    [Show full text]
  • Drug and Chemical Reference Guideline
    WISCONSIN DEPARTMENT OF AGRICULTURE, TRADE AND CONSUMER PROTECTION DIVISION OF FOOD AND RECREATIONAL SAFETY TITLE: Drug and Chemical Reference Guideline Document #: Replaces: New Revision Date: 1/21/2020 Page 1 of 6 General Guidelines: These drugs and substances are not to be used or • Drugs and administration equipment stored to not stored on dairy farms. These drugs are not eligible for contaminate milk or milk contact surfaces ELU privileges by veterinarians. • Non-lactating drugs separated from lactating drugs • Chloramphenicol using separate shelves or cabinets • Clenbuterol • Drugs properly labeled (see label requirements • Colloidal Silver below) • Diethylstilbestrol (DES) • Locked drug cabinets must be made accessible for • Dimethysulfoxide (DMSO) inspection • Dimetridazole • Drugs for animal species other than cattle must not • Dipyrone (Novine, No Pain) be stored in dairy facility • Estradiol Cypionate (ECP) • All bottles or packages in case lots properly labeled • Fluoroquinolones (sarafloxacin-Saraflox, orbafloxacin-Orbox, danofloxacin mesylate-A 180) Drug Labeling Requirements: • Furazolidone, Nitrofurazone, other Nitrofurans OTC Drugs: (over the counter) • Glycopeptides (vancomycin) • Name of Drug • Iononphores (Lasalocid) permitted for non-lactating • Active ingredients • Ipronidazole • Directions for use • Metronidazole and other Nitroimidazoles • Withholding/withdrawal or discard time for meat or • Phenylbutazone, “bute” (prohibited in dairy animals milk (even if zero) 20 months of age or older - no ELU allowed.) • Name
    [Show full text]
  • Structure and Origin of Uterine and Extragenital L=Ibroids Induced
    Structure and Origin of Uterine and Extragenital l=ibroids Induced Experimentally in the Guinea Pig by Prolonged Administration of Estrogens* Alexander Lipschotz, M.D., and Louis Vargas, Jr., M.D. (From Department o/ Experimental Medicine, National Health Service o/the Republic o/Chile, Santiago, Chile) (Received for publication December 13, x94o) The purpose of this communication is to present the These experimentally induced abdominal tumors findings of a detailed microscopical study of the sites present a smooth surface formed of a capsule com- of origin and stages of development of the subserous posed of flattened superficial cells (Plate 2, Figs. 2-A fibroid tumors induced in guinea pigs by prolonged and 2-B). The cells beneath the capsule resemble administration of estrogens. Details of treatment of fibroblasts. These cells have definite boundaries or the animals are given in the explanations of Plates I- 5. they are separated from each other by collagenous Subserous uterine tumors which can be induced in fibers (Plate 4, Fig. ix-C). guinea pigs by prolonged administration of estrogens, The masses of fibroid tumors arising from the apex as described by Nelson (26, 27), were found to be of the uterine horn may enclose the tubes or large fibroids. Lipschiitz, Iglesias, and Vargas (i3, 18, 22) tubal cysts. The demarcation between the muscular have shown that extragenital tumors in the abdominal coat of the tube and the tumor is not always sharp. cavity, induced by estrogens, also were fibroids. The In some instances, especially when the apical fibroid localization of these tumo~:s at various sites on the is small, the tumor is in close contact with an abun- uterus, pancreas, kidney, spleen, etc., have been de- dance of smooth muscle and adipose tissue (Plate 2, scribed by Iglesias (5), Vargas and Lipschiitz (32), Fig.
    [Show full text]
  • New Pharmacological Treatments for Equine Reproductive Management
    New Pharmacological Treatments for Equine Reproductive Management P. J. Burns, Ph.D.11,2,3,4, D. L. Thompson, Jr, Ph.D.5, W. A. Storer Ph.D.5 R. Gilley B.S1,2,3., C. Morrow, D.V.M.3, J. Abraham, B. S. 7 & R. H. Douglas, Ph.D. 1,2,3 1BioRelease Technologies LLC, Birmingham, AL 2BET Pharm, Lexington, KY 3 Mt Laurel Veterinary Pharmacy, Birmingham, 4Burns BioSolutions INC, Lexington, KY 5Animal Sciences Department, Louisiana State University, Baton Rouge, LA 6 Mobile Veterinary Practice, Amarillo, Tx, 7 Abraham Equine, Mendota Ranch, Canadian,Tx Introduction Loy (1970) reported that only 55% of mares bred annually produce live foals. Recent data from The Jockey Club (2006) indicate that only 37,025 of 64,123 (57.7%) of thoroughbred mares bred during 2005 produced live foals. This is considerably lower than foaling rates of 71 to 85%, which are reported on farms where extensive reproductive management is used. Overall, reproductive management has not improved much in the last 30 years. The long estrus period, with ovulation at any time from 1 to 10 days after the beginning of estrus, has made reproductive management of cyclic mares time-consuming, expensive and most importantly, inefficient. Furthermore, the confusion associated with the long and variable transition from anestrous to cyclicity in mares greatly magnifies the complexity of efficient reproductive management for this category of mares. There is a need to develop and capitalize on controlled breeding programs for the horse industry based on new advances in the understanding of cost effective hormonal control of reproduction in mares and stallions.
    [Show full text]
  • Pp375-430-Annex 1.Qxd
    ANNEX 1 CHEMICAL AND PHYSICAL DATA ON COMPOUNDS USED IN COMBINED ESTROGEN–PROGESTOGEN CONTRACEPTIVES AND HORMONAL MENOPAUSAL THERAPY Annex 1 describes the chemical and physical data, technical products, trends in produc- tion by region and uses of estrogens and progestogens in combined estrogen–progestogen contraceptives and hormonal menopausal therapy. Estrogens and progestogens are listed separately in alphabetical order. Trade names for these compounds alone and in combination are given in Annexes 2–4. Sales are listed according to the regions designated by WHO. These are: Africa: Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, South Africa, Swaziland, Togo, Uganda, United Republic of Tanzania, Zambia and Zimbabwe America (North): Canada, Central America (Antigua and Barbuda, Bahamas, Barbados, Belize, Costa Rica, Cuba, Dominica, El Salvador, Grenada, Guatemala, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago), United States of America America (South): Argentina, Bolivia, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Guyana, Paraguay,
    [Show full text]
  • Estradiol Cypionate: Summary Report
    Estradiol Cypionate: Summary Report Item Type Report Authors Yuen, Melissa V.; Gianturco, Stephanie L.; Pavlech, Laura L.; Storm, Kathena D.; Yoon, SeJeong; Mattingly, Ashlee N. Publication Date 2019-12 Keywords Estradiol cypionate; Compounding; Food, Drug, and Cosmetic Act, Section 503B; Food and Drug Administration; Outsourcing facility; Drug compounding; Legislation, Drug; United States Food and Drug Administration Rights Attribution-NoDerivatives 4.0 International Download date 27/09/2021 15:15:19 Item License http://creativecommons.org/licenses/by-nd/4.0/ Link to Item http://hdl.handle.net/10713/12106 Summary Report Estradiol cypionate Prepared for: Food and Drug Administration Clinical use of bulk drug substances nominated for inclusion on the 503B Bulks List Grant number: 2U01FD005946 Prepared by: University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) University of Maryland School of Pharmacy December 2019 This report was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award (U01FD005946) totaling $2,342,364, with 100 percent funded by the FDA/HHS. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement by, the FDA/HHS or the U.S. Government. 1 Table of Contents REVIEW OF NOMINATIONS ................................................................................................... 4 METHODOLOGY ...................................................................................................................
    [Show full text]
  • Gender-Affirming Hormone Therapy
    GENDER-AFFIRMING HORMONE THERAPY Julie Thompson, PA-C Medical Director of Trans Health, Fenway Health March 2020 fenwayhealth.org GOALS AND OBJECTIVES 1. Review process of initiating hormone therapy through the informed consent model 2. Provide an overview of masculinizing and feminizing hormone therapy 3. Review realistic expectations and benefits of hormone therapy vs their associated risks 4. Discuss recommendations for monitoring fenwayhealth.org PROTOCOLS AND STANDARDS OF CARE fenwayhealth.org WPATH STANDARDS OF CARE, 2011 The criteria for hormone therapy are as follows: 1. Well-documented, persistent (at least 6mo) gender dysphoria 2. Capacity to make a fully informed decision and to consent for treatment 3. Age of majority in a given country 4. If significant medical or mental health concerns are present, they must be reasonably well controlled fenwayhealth.org INFORMED CONSENT MODEL ▪ Requires healthcare provider to ▪ Effectively communicate benefits, risks and alternatives of treatment to patient ▪ Assess that the patient is able to understand and consent to the treatment ▪ Informed consent model does not preclude mental health care! ▪ Recognizes that prescribing decision ultimately rests with clinical judgment of provider working together with the patient ▪ Recognizes patient autonomy and empowers self-agency ▪ Decreases barriers to medically necessary care fenwayhealth.org INITIAL VISITS ▪ Review history of gender experience and patient’s goals ▪ Document prior hormone use ▪ Assess appropriateness for gender affirming medical
    [Show full text]
  • OTS-8120.6 Chapter 246-886
    AMENDATORY SECTION (Amending WSR 15-13-086, filed 6/15/15, effective 7/16/15) WAC 246-887-020 Uniform Controlled Substances Act. (1) ((Con- sistent with the concept of uniformity where possible with the federal regulations for controlled substances (21 C.F.R.), the federal regula- tions are specifically made applicable to registrants in this state by virtue of RCW 69.50.306. Although those regulations are automatically applicable to registrants in this state,)) The pharmacy quality assur- ance commission (commission) ((is nevertheless adopting as its own regulations the existing regulations of the federal government pub- lished in)) adopts Title 21 of the Code of Federal Regulations ((re- vised as of April 1, 1991, and all references made therein to the di- rector or the secretary shall have reference to the commission, and)). The following sections ((are not applicable)) do not apply: Section ((1301.11-.13, section 1301.31, section 1301.43-.57)) 1301.13, section 1301.33, section 1301.35-.46, section 1303, section ((1308.41-.48)) 1308.41-.45, and section 1316.31-.67. ((The following specific rules shall take precedence over the federal rules adopted herein by refer- ence, and therefore any inconsistencies shall be resolved in favor of the following specific rules.)) Any inconsistencies between Title 21 of the Code of Federal Regulations sections 1300 through 1321 and chapter 246-887 WAC should be resolved in favor of chapter 246-887 WAC. Further, nothing in these rules applies to the production, pro- cessing, distribution, or possession of marijuana as authorized and regulated by the Washington state liquor and cannabis board.
    [Show full text]
  • Progesterone and Estradiol Benzoate. (Iii) Limitations
    Food and Drug Administration, HHS § 522.1940 0.28 milligrams of isopropamide) in (ii) Indications for use. For increased buffered aqueous solution. rate of weight gain. (b) Sponsor. See No. 000069 in (iii) Limitations. For use in suckling § 510.600(c) of this chapter. beef calves (at least 45 days of age) up (c) Conditions of use. (1) The drug is to 400 pounds (lb) of body weight. For used in dogs and cats in which gastro- subcutaneous ear implantation, one intestinal disturbances are associated dose per animal. Do not use in bull with emotional stress. calves intended for reproduction. Safe- (2) Dosage is administered by sub- ty and effectiveness have not been es- cutaneous injection twice daily as fol- tablished in veal calves. A withdrawal lows: period has not been established for this product in preruminating calves. Do Dosage in Weight of animal in pounds Milliliters not use in calves to be processed for veal. Up to 4 ................................................................. 0.25 (2) Steers—(i) Amount—(A) 200 mg pro- 5 to 14 ................................................................. 0.5–1 15 to 30 ............................................................... 2–3 gesterone and 20 mg estradiol benzoate 30 to 45 ............................................................... 3–4 (one implant consisting of 8 pellets, 45 to 60 ............................................................... 4–5 each pellet containing 25 mg progester- Over 60 ................................................................ 6 one and 2.5 mg estradiol benzoate) per implant dose. Following the last injection, admin- (B) 200 mg progesterone and 20 mg es- ister prochlorperazine and tradiol benzoate (one implant con- isopropamide sustained release cap- sisting of 9 pellets, each of 8 pellets sules as indicated. containing 25 mg progesterone and 2.5 (3) For use only by or on the order of mg estradiol benzoate, and 1 pellet con- a licensed veterinarian.
    [Show full text]
  • Profiles of Circulating Estradiol-17Β After Different Estrogen Treatments in Lactating Dairy Cows
    Anim. Reprod., v.2, n.4, p.224-232, Oct./Dec. 2005 Profiles of circulating estradiol-17β after different estrogen treatments in lactating dairy cows A.H. Souza1, A.P. Cunha1, D.Z. Caraviello1, M.C. Wiltbank1,2 1Department of Dairy Science, 1675 Observatory Drive, University of Wisconsin, Madison, WI, USA 53706 Abstract Washburn et al., 2002). One of the physiological aspects that may affect reproductive efficiency in The objective of this study was to characterize lactating dairy cows is the elevated metabolism of the circulating concentrations of estradiol-17β (E-17β) estradiol-17β (E-17β; Sangsritavong et al., 2002). This after treatment with different types or doses of estrogens high E-17β metabolism appears to be due to the in the absence (Experiment 1) or presence (Experiment 2) elevated liver blood flow that is coincident with of a dominant follicle in lactating cows. In Experiment 1, elevated dry matter intake in lactating dairy cows cows (n = 12) had all follicles > 5 mm removed by (Sangsritavong et al., 2002). High rates of E-17β ultrasound-guided follicular aspiration every 12 h metabolism result in reduced circulating E-17β throughout the blood sampling period. Estrogen concentrations in lactating cows compared to non- treatments started 48 h after the first follicular aspiration. lactating cows (Sartori et al., 2002a; 2004) and in Treatments were: no treatment, E-17β (0.5 mg), or lactating cows with high milk production compared to estradiol benzoate (EB, 0.5 mg). Seven days after the cows with low production (Lopez et al., 2004; 2005). end of the first trial, cows were then re-randomized to Since E-17β is involved in many aspects of reproductive receive: no treatment, E-17β (1.0 mg), EB (1.0 mg), or physiology, this reduction in circulating E-17β could estradiol cypionate (ECP, 1.0 mg).
    [Show full text]