Medically reviewed by Drugs.com. Last updated on Oct 14, 2019.
Common Name(s): Hormonil, Micronized progesterone, MyGest, Natural progesterone, Phytoprolief, Pro-Gest, Progesta-Eze, Progestelle, Progesterone cream, Prov-Juven, Women to Women Body Cream, Young Again Natural Progesterone Cream
Topical progesterone is used to manage menopause-related symptoms, such as hot flashes, low libido, and mood swings. Clear evidence of a progesterone benefit in improving bone density or cardiovascular markers, or for the prevention of endometrial proliferation, is lacking. Topical progesterone has also been studied for the management of cyclic breast pain and for skin elasticity and firmness in postmenopausal women.
Most trials evaluated topical progesterone 40 mg daily either as a single dose or 20 mg twice daily for menopausal symptoms.
Information regarding topically applied progesterone in pregnancy and lactation is lacking.
None well documented.
Clinical trials report few adverse events, with most no different from those of the placebo comparator. A higher incidence of headache and postmenopausal bleeding has been reported.
Research reveals no information regarding the toxicity of topical progesterone.
Phytoestrogens, structurally similar to human estrogen and progesterone, are synthesized by more than 5,000 plants. Progesterone can be converted from the sterol diosgenin found in plants such as soybeans and wild yam.1 This monograph is limited to evidence for progesterone cream and does not include references to wild yam or soy. (See Wild Yam or Soy monographs for more information.) Despite claims that natural progesterone is plant-based and therefore from a natural source, many synthesized progesterones are also plant-derived and are chemically identical to progesterone of the ovarian origin.2
"Natural" progesterone cream has been available in the United States for at least 20 years as an over-the-counter preparation and is not regulated by the FDA.1, 3, 4 Transdermal delivery was proposed as an alternative to the oral route because approximately 90% of progesterone is enzymatically inactivated in the gut and liver, and results in undesirable metabolites are produced.1
Claims for the use of topical natural progesterone include the prevention and treatment of osteoporosis and low libido, as well as the management of menopausal symptoms, including hot flashes, and enhancement of mood and psychological well being.1, 3
Progesterone, a principle of corpus luteum, is the primary endogenous progestational substance. Progestins (progesterone and derivatives) transform proliferative endometrium into secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo.5
Progesterone receptors have been identified in whole skin, keratinocytes, and fibroblasts.1
Micronized progesterone is used in oral and topical preparations to enhance absorption.2
Uses and Pharmacology
Clinical studies have been conducted to describe the pharmacokinetics of topical progesterone, with most studies finding major increases in salivary progesterone and only moderate increases in serum progesterone levels. Wide variations in measured progesterone levels are also a feature of these studies.1, 6, 7, 8, 9, 10 In a crossover study, topical progesterone 40 mg twice daily showed no difference compared with oral progesterone 200 mg in the 24-hour area under the curve (AUC) for whole blood progesterone3 while another kinetic study using a daily progesterone 60 mg cream achieved serum progesterone levels similar to luteal levels (more than 3 ng/mL).11 A clinical trial evaluating the effect of progesterone on bone density found increases in serum progesterone for up to 6 months with no further accumulation. At 3 years, the mean serum progesterone level was 3.54 nmol/L.12
Various mechanisms have been proposed to explain the observed low plasma levels of progesterone following topical application. These include uptake by the red blood cells, rapid conversion to 5-alpha-reduced progestin, and rapid clearance from the serum by salivary and hepatic excretion, combined with slow transdermal absorption.1, 7, 9 A "priming" effect of the skin resulting in increased absorption after a few days of administration has also been suggested.7, 13
Genital lichen sclerosus
A systematic review and meta-analysis of randomized controlled trials that investigated use of topical interventions for genital lichen sclerosus found no evidence to support the use of topical progesterone as a treatment option. Of the 7 studies that met inclusion criteria, only 1 evaluated topical progesterone (2% cream) and found no significant difference compared to placebo after 3 months application.50
Studies in animals are limited. In a study conducted in rats, topical progesterone was found to be effectively and biologically actively absorbed. A similar distribution in tissues was found following intramuscular administration. Metabolism was also similar.14
Debate exists about the relevance of plasma and salivary progesterone as surrogate indicators of clinical efficacy.1, 8, 9, 15 Clear evidence of a progesterone benefit in improving bone density or cardiovascular markers, or for the prevention of endometrial proliferation is lacking.6, 16, 17, 18, 19
In an open-label study, topical progesterone 40 mg daily applied for over 1 year did not provide adequate opposition to endometrial hyperplasia as determined by endometrial histology and bleeding patterns in 41 postmenopausal women.20, 21 A small clinical crossover trial (N = 26) found topical progesterone 40 mg daily to exert a similar effect on the endometrium as standard oral progesterone.22 In a large (N = 223), double-blind, randomized trial, topical progesterone (Progestelle) applied for over 6 months showed no difference compared with placebo for psychological, somatic, or vasomotor menopause-related symptoms. Dosages of progesterone 5, 20, 40, and 60 mg daily were tested. A string placebo effect was observed. No histological effect of topical progesterone on the endometrium was demonstrated.23 In a randomized clinical study, results with topical progesterone 32 mg did not differ from those with placebo for vasomotor symptoms, mood, or libido, and showed no effect on blood lipids or bone metabolic markers.10
In a randomized clinical trial (N = 102), topical progesterone 20 mg daily showed no protective effect on bone density at 1 year and no change in the lipid profile versus placebo. However, an improvement in vasomotor symptoms was recorded.24 A 2-year study evaluating the effect of soy and transdermal progesterone on bone mineral density in postmenopausal women found progesterone alone to have protective effects on the lumbar spine but not hip bone, but the positive effect was attenuated when used in combination with soy milk.25 No effect on bone density or plasma lipids was found for topical progesterone 40 mg daily in a large, double-blind, randomized clinical trial (N = 131 postmenopausal women).12
Topical progesterone was no better than placebo for the management of cyclic breast pain in a small clinical trial.26 A progesterone 2% cream increased the elasticity and firmness of skin in postmenopausal women in a small study.13
Commercial progesterone creams vary in concentration but are generally in the range of 1.5% to 3% progesterone. Most trials evaluated progesterone 40 mg daily either as a single dose or 20 mg twice daily for menopausal symptoms.12, 20, 21
Pregnancy / Lactation
Information regarding topically applied progesterone in pregnancy and lactation is lacking.
Anticoagulants: Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. The use of an estrogen derivative may modify the thromboembolic risk associated with this combination. Numerous comorbid states and other patient characteristics may modify the thromboembolic risk associated with this combination. Recommendations for management of this interaction may differ depending on the indication for progestin treatment (eg, for hormone replacement therapy vs. contraception). Consider therapy modification.51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68
Antidiabetic agents: Hyperglycemia-associated agents may diminish the therapeutic effect of antidiabetic agents. Monitor therapy.69, 70, 71, 72, 73, 74, 75, 76
Antifungal agents (vaginal): Antifungal agents (vaginal) may diminish the therapeutic effect of progesterone. This interaction only applies to the vaginal progesterone product (Endometrin) and vaginal antifungal products. Avoid combination.77, 78
Bosentan: Bosentan may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.79, 80
C1 inhibitors: Progestins may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy.81, 82, 83, 84, 85
Cyclosporine (systemic): Progestins may enhance the hepatotoxic effect of cyclosporine(systemic). Progestins may increase the serum concentration of cyclosporine (systemic). Monitor therapy.30, 31
CYP2C19 inducers (strong): CYP2C19 inducers (strong) may increase the metabolism of CYP2C19 substrates. Consider therapy modification.32, 33
CYP3A4 inducers (moderate): CYP3A4 inducers (moderate) may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Monitor therapy.86, 87
CYP3A4 inducers (strong): CYP3A4 inducers (strong) may increase the metabolism of CYP3A4 substrates. Consider therapy modification.32, 33
Deferasirox: Deferasirox may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.34
Enzalutamide: Enzalutamide may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Consider therapy modification.88, 89
Herbs (progestogenic properties): Herbs (progestogenic properties) may enhance the adverse/toxic effect of progestins. Monitor therapy.35
Ivosidenib: Ivosidenib may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Monitor therapy.90
Lomitapide: CYP3A4 inhibitors (weak) may increase the serum concentration of lomitapide. Consider therapy modification.36
Mitotane: Mitotane may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Consider therapy modification.91, 92, 93, 94, 95, 96, 97
Pitolisant: Pitolisant may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Consider therapy modification.98, 99
Pomalidomide: Progestins may enhance the thrombogenic effect of pomalidomide. Canadian labeling specifically recommends avoiding use of hormonal contraceptives and recommends caution with use of hormone replacement therapy. US labeling does not contain these specific warnings. Consider therapy modification.37
Sarilumab: Sarilumab may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Monitor therapy.100, 107, 108
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of silodosin. Avoid combination.38
Siltuximab: Siltuximab may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Monitor therapy.100, 101
St. John’s wort: St John's wort may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Consider therapy modification.33, 86, 102, 103, 104
Tocilizumab: Tocilizumab may decrease the serum concentration of CYP3A4 substrates (high risk with inducers). Monitor therapy.39, 40, 41
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of topotecan. Avoid combination.42, 43, 44, 45, 46, 47, 48, 49
Ulipristal: Progestins may diminish the therapeutic effect of ulipristal. Ulipristal may diminish the therapeutic effect of progestins. Avoid combination.105, 106
Clinical trials report few adverse events, with most no different from those of the placebo comparator.11, 23 A higher incidence of headache and postmenopausal bleeding was associated with topical progesterone in 1 large clinical study.23 Water retention, breast engorgement, increased body weight, and mild to moderate depression have been documented in case reports following long-term use.27
While progesterone cream may be helpful for women with proven low progesterone levels, for women experiencing symptoms due to relative progesterone deficits, meaning more or less normal progesterone levels but with estrogen excess, progesterone cream may increase the hormonal load in the body. Aromatase enzymes in adipose cells below the dermis convert androgens, including progesterone, into estrogen. Therefore, women with hyperestrogenism may not benefit and may even be harmed by progesterone supplementation if it is not prescribed appropriately.28, 29
Research reveals no information regarding the toxicity of topical progesterone.
1. Elshafie MA, Ewies AA. Transdermal natural progesterone cream for postmenopausal women: inconsistent data and complex pharmacokinetics. J Obstet Gynaecol
2. "Natural" progesterone creams for postmenopausal women. Drug Ther Bull
3. Hermann AC, Nafziger AN, Victory J, Kulawy R, Rocci ML Jr, Bertino JS Jr. Over-the-counter progesterone cream produces significant drug exposure compared to a food and drug administration-approved oral progesterone product. J Clin Pharmacol
4. MacFarland SA. Use of Pro-Gest cream in postmenopausal women. Lancet
5. Progesterone. Drug Facts and Comparisons
. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health Inc; May 2010. Accessed June 9, 2011.
6. Gambrell RD Jr. Progesterone skin cream and measurements of absorption. Menopause
7. Carey BJ, Carey AH, Patel S, Carter G, Studd JW. A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women. BJOG
8. O'Leary P, Feddema P, Chan K, Taranto M, Smith M, Evans S. Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women. Clin Endocrinol (Oxf)
9. Lewis JG, McGill H, Patton VM, Elder PA. Caution on the use of saliva measurements to monitor absorption of progesterone from transdermal creams in postmenopausal women. Maturitas
10. Wren BG, Champion SM, Willetts K, Manga RZ, Eden JA. Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, moods, and quality of life for postmenopausal women. Menopause
11. Burry KA, Patton PE, Hermsmeyer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol
. 1999;180(6, pt 1):1504-1511.10368498
12. Benster B, Carey A, Wadsworth F, Griffin M, Nicolaides A, Studd J. Double-blind placebo-controlled study to evaluate the effect of Pro-Juven progesterone cream on atherosclerosis and bone density. Menopause Int
13. Holzer G, Riegler E, Hönigsmann H, Farokhina S, Schmidt JB. Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study [published correction appears in Br J Dermatol
. 2005;153(3):1092]. Br J Dermatol
14. Waddell BJ, O'Leary PC. Distribution and metabolism of topically applied progesterone in a rat model. J Steroid Biochem Mol Biol
15. Lee JR. Use of Pro-Gest cream in postmenopausal women. Lancet
16. Stevenson JC, Purdie DW. Use of Pro-Gest cream in postmenopausal women. Lancet
17. Cooper A, Spencer C, Whitehead MI, Ross D, Barnard GJ, Collins WP. Systemic absorption of progesterone from Progest cream in postmenopausal women. Lancet
18. Scant evidence for progesterone cream. Harv Womens Health Watch
19. Leonetti HB, Wilson KJ, Anasti JN. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Fertil Steril
20. Vashisht A, Wadsworth F, Carey A, Carey B, Studd J. Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime. BJOG
21. Vashisht A, Wadsworth F, Carey A, Carey B, Studd J. A study to look at hormonal absorption of progesterone cream used in conjunction with transdermal estrogen. Gynecol Endocrinol
22. Leonetti HB, Landes J, Steinberg D, Anasti JN. Transdermal progesterone cream as an alternative progestin in hormone therapy. Altern Ther Health Med
23. Benster B, Carey A, Wadsworth F, Vashisht A, Domoney C, Studd J. A double-blind placebo-controlled study to evaluate the effect of Progestelle progesterone cream on postmenopausal women. Menopause Int
24. Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol
25. Lydeking-Olsen E, Beck-Jensen JE, Setchell KD, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss—a 2 year randomized, placebo-controlled trial. Eur J Nutr
26. McFadyen IJ, Raab GM, Macintyre CC, Forrest AP. Progesterone cream for cyclic breast pain. BMJ
27. Ilyia EF, McLure D, Farhat MY. Topical progesterone cream application and overdosing. J Altern Complement Med
28. Reed MJ. The role of aromatase in breast tumors. Breast Cancer Res Treat
29. Pasqualini JR. Breast cancer and steroid meatabolizing enzymes: the role of progestogens. Maturitas
. 2009;65(suppl 1):S17-S21.19962254
30. Deray G, Le Hoang P, Cacoub P, et al. Oral contraceptive interaction with cyclosporine. Lancet
31. Maurer G. Metabolism of cyclosporine. Transplant Proc
. 1985;17(Suppl 1):19.3895660
32. Bjornsson TD, Callaghan JT, Einolf HJ, et al. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol
33. U.S. Food and Drug Administration. Guidance for Industry: Drug Interaction Studies — Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm292362.pdf
. Accessed March 18, 2013.
34. Exjade (deferasirox) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; October 2008.
35. Zava DT, Dollbaum CM and Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med
36. Juxtapid [package insert]. Cambridge, MA: Aegerion Pharmaceuticals, Inc; December 2012.
37. Pomalyst (polamidomide) [prescribing information]. Summit, NJ: Celgene Corporation; April 2015.
38. Rapaflo [package insert]. Corona, CA: Watson Pharmaceuticals, Inc; September 2008.
39. Schmitt C, Kuhn B, Zhang X, et al. Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheumatoid arthritis. Clin Pharmacol Ther
40. Actemra [package insert]. San Francisco, CA: Genentech Inc; April 2011.
41. Aitken AE, Morgan ET. Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6, and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos
42. Hycamtin [package insert]. Research Triangle Park, NC: GlaxoSmithKline; October 2007.
43. Kruijtzer CMF, Beijnen JH, Rosing H, et al. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol
44. Jonker JW, Smit JW, Brinkhuis RF, et al. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst
45. Hendricks CB, Rowinsky EK, Grochow LB, et al. Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res
46. Chen AY, Yu C, Potmesil M, et al. Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res
47. Leggas M, Adachi M, Scheffer GL, et al. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol Cell Biol
48. Maliepaard M, van Gastelen MA, Tohgo A, et al. Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res
49. Maliepaard M, van Gastelen MA, de Jong LA, et al. Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res
50. Chi CC, Kirtschig G, Baldo M, Lewis F, Wang SH, Wojnarowska F. Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus. J Am Acad Dermatol
51. American College of Obstetricians and Gynecologists. Practice bulletin: Use of hormonal contraception in women with coexisting medical conditions. http://csmcobgynresidents.files.wordpress.com/2010/02/contraception-in-women-with-coexisting-medical-conditions-pb-731.pdf
Published June 2006. Accessed October 2013.
52. The American College of Obstetricians and Gynecologists. Committee opinion: Hormone therapy and heart disease. http://www.acog.org/Resources%20And%20Publications/Committee%20Opinions/Committee%20on%20Gynecologic%20Practice/Hormone%20Therapy%20and%20Heart%20Disease.aspx
Published June 2013. Accessed October 2013.
(norethindrone acetate) [prescribing information]. Pomona, NY: Duramed Pharmaceuticals, Inc; July 2007.
54. British Menopause Society and Women's Health Concern. The 2013 British Menopause Society & Women’s Health Concern recommendations on hormone replacement therapy. http://min.sagepub.com/content/19/2/59
. Published May 2013. Accessed October 2013.
55. CDC. Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use, 2010. http://www.cdc.gov/mmwr/pdf/rr/rr59e0528.pdf
. Published May 2010. Accessed October 2013.
56. FDA. U.S. Food and Drug Administration. FDA drug safety communication: Updated information about the risk of blood clots in women taking birth control pills containing drospirenone. FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm299305.htm
. Updated April 2012. Accessed October 2013.
57. International Menopause Society. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health. http://www.imsociety.org/pdf_files/ims_recommendations/updated_ims_recommendations_on_postmenopausal_hormone_therapy_and_preventive_strategies_for_midlife_health_01_06_11.pdf Published 2011. Accessed October 2013.
58. Ortho-cyclen (norgestimate/ethinyl estradiol) [prescribing information]. Raritan, NJ: Ortho-McNeill-Janssen Pharmaceuticals, Inc; August 2008.
59. Ortho-Micronor (norethindrone) [prescribing information]. Raritan, NJ: Ortho McNeil Pharmaceuticals, Inc; June 2008.
60. North American Menopause Society. The 2012 hormone therapy position statement of the North American Menopause Society. http://www.menopause.org/docs/default-document-library/psht12.pdf?sfvrsn=2
. Accessed 2012.
61. Premarin (conjugated estrogens) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; June 2011.
62. Prempro (conjugated estrogens and medroxyprogesterone) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2012.
63. Prometrium (progesterone) [prescribing information]. North Chicago, IL: Abbott Laboratories; Nobember 2011.
64. Provera (medroxyprogesterone acetate) [prescribing information]. New York, NY: Pharmacia and Upjohn Company Division of Pfizer, Inc; September 2007.
65. Royal College of Obstetricians and Gynaecologists. Venous thromboembolism and hormone replacement therapy. http://www.rcog.org.uk/files/rcog-corp/GTG19VTEHRT310511.pdf. Published May 2011. Accessed October 2013.
66. Royal College of Obstetricians and Gynecologists. Faculty of sexual and reproductive healthcare clinical guidance: Progestogen-only pills. http://www.fsrh.org/pdfs/CEUGuidanceProgestogenOnlyPill09.pdf. Published June 2009. Accessed October 2013.
67. United States Preventative Services Task Force. Menopausal hormone therapy for the primary prevention of chronic conditions. http://www.uspreventiveservicestaskforce.org/uspstf12/menohrt/menohrtfinalrs.htm#ref15. Published October 2013. Accessed October 2013.
68. World Health Organization. Medical eligibility criteria for contraceptive use, fourth edition. http://whqlibdoc.who.int/publications/2010/9789241563888_eng.pdf
. Published 2009. Accessed October 2013.
(somatropin) [prescribing information]. Winnipeg, Canada: Cangene Corporation; January 2008.
(glimepiride) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; October 2013.
(chlorothiazide) [prescribing information]. Minneapolis, MN: Paddock Laboratories Inc; June 2009.
(niacin extended-release) [prescribing information]. North Chicago, IL: Abbott Laboratories; February 2013.
(insulin aspart) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; January 2015.
(atazanavir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; June 2014.
(pramlintide) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP, June 2014.
(temsirolimus) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals; February 2015.
(progesterone) vaginal insert [prescribing information]. Parsippany, NJ: Ferring Pharmaceuticals Inc; February 2008.
(progesterone) vaginal tablets [product monograph]. North York, Ontario, Canada: Ferring Inc; May 2015.
79. Dingemanse J, Schaarschmidt D, Van Giersbergen PL. Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmcokinet.
80. Tracleer (bosentan) [prescribing information]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc, 1999.
(C1 esterase inhibitor [human]) [prescribing information]. Kankakee, IL: CSL Behring LLC; February 2014.
(C1 esterase inhibitor [human]) [prescribing information]. Exton, PA: ViroPharma Biologics Inc; February 2014.
83. Gandhi PK, Gentry WM, Bottorff MB. Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Association adverse event reporting system database. Pharmacotherapy
84. Horstick G, Berg O, Heimann A, et al. Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects. Circulation
(C1 esterase inhibitor [recombinant]) [prescribing information]. Raleigh, NC: Santarus Inc; July 2014.
86. Bjornsson TD, Callaghan JT, Einolf HJ, et al; Pharmaceutical Research and Manufacturers of America Drug Metabolism/Clinical Pharmacology Technical Working Groups. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol
87. US Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Guidance for Industry: Drug Interaction Studies -- Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm292362.pdf
. Published February 2012. Accessed March 18, 2013.
88. Gibbons JA, de Vries M, Krauwinkel W, et al. Pharmacokinetic drug interaction studies with enzalutamide. Clin Pharmacokinet
(enzalutamide) [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc; October 2015.
90. Tibsovo (ivosidenib) [prescribing information]. Cambridge, MA: Agios Pharmaceuticals Inc; July 2018.
91. Chortis V, Taylor AE, Schneider P, et al. Mitotane therapy in adrenocortical cancer induces CYP3A4 and inhibits 5?-reductase, explaining the need for personalized glucocorticoid and androgen replacement. J Clin Endocrinol Metab
92. Cuddy PG, Loftus LS. Influence of mitotane on the hypoprothrombinemic effect of warfarin. South Med J
93. Hague RV, May W, Cullen DR. Hepatic microsomal enzyme induction and adrenal crisis due to o,p'DDD therapy for metastatic adrenocortical carcinoma. Clin Endocrinol (Oxf)
94. Lysodren (mitotane) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company, Novemeber 2013.
95. Robinson BG, Hales IB, Henniker AJ, et al. The effect of o,p'DDD on adrenal steroid replacement therapy requirements. Clin Endocrinol (Oxf)
96. Takeshita A, Igarashi-Migitaka J, Koibuchi N, Takeuchi Y. Mitotane induces CYP3A4 expression via activation of the steroid and xenobiotic receptor. J Endocrinol
97. van Erp NP, Guchelaar HJ, Ploeger BA, Romijn JA, Hartigh Jd, Gelderblom H. Mitotane has a strong and a durable inducing effect on CYP3A4 activity. Eur J Endocrinol
98. Wakix (pitolisant) [UK summary of product characteristics]. Paris, France: Bioprojet Pharma; March 2017a.
99. Wakix (pitolisant) [EMA summary of product characteristics]. Paris, France: Bioprojet Pharma; March 2017b.
100. Aitken AE, Morgan ET. Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6, and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos
(siltuximab) [prescribing information]. Horsham, PA: Janssen Biotech Inc; April 2014.
102. Di YM, Li CG, Xue CC, Zhou SF. Clinical drugs that interact with St. John's wort and implication in drug development. Curr Pharm Des
103. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs
104. Zhou SF, Lai X. An update on clinical drug interactions with the herbal antidepressant St. John's wort. Curr Drug Metab
(ulipristal acetate) [prescribing information]. Charleston, SC: Afaxys, Inc.; March 2015.
(ulipristal acetate) [product monograph]. Mississauga, Ontario, Canada: Actavis Specialty Pharmaceuticals Co; June 2013.
107. Kevzara (sarilumab) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; May 2017.
108. Lee EB, Daskalakis N, Xu C, et al. Disease-drug interaction of sarilumab and simvastatin in patients with rheumatoid arthritis. Clin Pharmacokinet
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