Identification

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Name
Drospirenone
Accession Number
DB01395
Type
Small Molecule
Groups
Approved
Description

Drospirenone is a synthetic progestin commonly found in the popular oral contraceptive, Yaz in combination with Ethinyl estradiol.19 Aside from its contraceptive effects, drospirenone is used with estrogens to control acne and premenstrual dysphoric disorder (PMDD).

Drospirenone has been the subject of widespread safety concern due to the possibility of an increased risk of venous thromboembolism associated with its use.4,7 In 2012, however, a safety statement by the FDA concluded that the increase in the risk of thromboembolism resulting from the use of drospirenone remains unclear, as studies regarding this risk are conflicting. Some studies have demonstrated a significantly increased risk and some demonstrating no risk of thromboembolic events. In its statement, the FDA has mentioned that increased risk of venous thromboembolism with oral contraceptives such as drospirenone exists but remains lower than the risk of this condition during pregnancy and during the postpartum period, and this should be considered when assessing potential risks of hormonal contraceptive use.21

Structure
Thumb
Synonyms
  • 1,2-Dihydrospirorenone
  • 6β,7β;15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone
  • Dehydrospirorenone
  • Drospirenona
  • Drospirenone
  • Drospirénone
  • Drospirenonum
  • DRSP
External IDs
ZK 30595 / ZK-30595
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SlyndTablet, film coated4 mg/1OralExeltis Usa, Inc.2019-06-06Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AngeliqDrospirenone (0.5 mg/1) + Estradiol (1 mg/1)Tablet, film coatedOralBayer HealthCare Pharmaceuticals Inc.2005-11-28Not applicableUs
AngeliqDrospirenone (0.5 mg/1) + Estradiol (1 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2010-09-29Not applicableUs
AngeliqDrospirenone (1.0 mg) + Estradiol (1.0 mg)TabletOralBayer2008-10-20Not applicableCanada
AngeliqDrospirenone (0.25 mg/1) + Estradiol (0.5 mg/1)Tablet, film coatedOralBayer HealthCare Pharmaceuticals Inc.2012-02-29Not applicableUs
BeyazDrospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1) + Levomefolate calcium (0.451 mg/1) + Levomefolate calcium (0.451 mg/1)KitOralBayer HealthCare Pharmaceuticals Inc.2010-10-07Not applicableUs50419 40720180113 27003 xgvnkl
Drospirenone and ethinyl estradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)KitOralCamber Pharmaceuticals, Inc.2019-03-22Not applicableUs
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)KitOralJubilant Cadista Pharmaceuticals Inc2018-11-30Not applicableUs
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.03 mg/1)KitOralGlenmark Pharmaceuticals Inc.,Usa2016-03-25Not applicableUs
Drospirenone and Ethinyl EstradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.02 mg/1)KitOralGlenmark Pharmaceuticals Inc.,Usa2015-08-17Not applicableUs
Drospirenone and ethinyl estradiolDrospirenone (3 mg/1) + Ethinylestradiol (0.03 mg/1)KitOralApotex Corp.2018-03-202021-08-21Us
Categories
UNII
N295J34A25
CAS number
67392-87-4
Weight
Average: 366.4932
Monoisotopic: 366.219494826
Chemical Formula
C24H30O3
InChI Key
METQSPRSQINEEU-HXCATZOESA-N
InChI
InChI=1S/C24H30O3/c1-22-6-3-12(25)9-17(22)13-10-14(13)20-16(22)4-7-23(2)21(20)15-11-18(15)24(23)8-5-19(26)27-24/h9,13-16,18,20-21H,3-8,10-11H2,1-2H3/t13-,14+,15-,16+,18+,20-,21+,22-,23+,24+/m1/s1
IUPAC Name
(1R,2R,4R,10R,11S,14S,15S,16S,18S,19S)-10,14-dimethylspiro[hexacyclo[9.8.0.0²,⁴.0⁵,¹⁰.0¹⁴,¹⁹.0¹⁶,¹⁸]nonadecane-15,2'-oxolan]-5-ene-5',7-dione
SMILES
[H][C@@]12C[C@]1([H])[C@@]1([H])[C@]3([H])[C@]4([H])C[C@]4([H])[C@@]4(CCC(=O)O4)[C@@]3(C)CC[C@]1([H])[C@@]1(C)CCC(=O)C=C21

Pharmacology

Indication

Drospirenone, in combination with ethinyl estradiol, is indicated as an oral contraceptive for the prevention of pregnancy. In addition to its use for contraceptive effects, this combination is used to treat moderate acne vulgaris and the symptoms of premenstrual dysphoric disorder.19,20 The drug has approved indications for combination with estrogens for the treatment of menopause-associated symptoms, such as vasomotor symptoms and vulvovaginal atrophy. Drospirenone combined with estrogen may also may aid in the prevention of osteoporosis in women who have been post-menopausal for at least a year and are not candidates for other therapies.23,25 It can sometimes be found in preparations containing estrogen and folic acid for folic acid replenishment during oral contraception.26

When used for the treatment of acne vulgaris, drospirenone-containing contraceptives should only be used in women ≥14 years of age who have experienced menarche, desire oral contraception, and do not have any contraindications to oral contraceptives.20 Off-label uses for this drug include the treatment of menstrual irregularities, dysmenorrhea, hirsutism, and endometriosis.1,11

Associated Conditions
Associated Therapies
Pharmacodynamics

Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing pregnancy. It has antiandrogen effects, improving acne and hirsutism. When combined with ethinyl estradiol, it has been shown to have favorable effects on the plasma lipid profile.20 Due to its similarity to naturally occurring progesterone, drospirenone is thought to be associated with a lower incidence of progesterone contraceptive related adverse effects, such as breast tenderness and mood swings.1

A note on venous thromboembolism risk and antimineralcorticoid effects

As with other oral contraceptives, the risk of venous thromboembolism and cardiovascular events may be increased when drospirenone is taken. The risk is especially higher in smokers and women aged 35 and older. Women taking this drug should be advised not to smoke. In addition, drospirenone, due to its antimineralcorticoid effects, may increase the risk of hyperkalemia. Patients at high risk for hyperkalemia should not be administered this drug. Consult the official prescribing information for detailed and updated information on the cardiovascular and other risks associated with drospirenone use.19,20,23

Mechanism of action

Drospirenone and ethinyl estradiol in combination suppress the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH), preventing ovulation. Other changes induced by this drug which may aid in the prevention of pregnancy include alterations in cervical mucus consistency, hindering sperm movement, and lowering the chance of embryo implantation.20

Drospirenone is an analog of the diuretic spironolactone, which exerts anti-mineralocorticoid activity, blocking aldosterone receptors, which increases sodium and water excretion.1 Studies in animals have demonstrated that drospirenone administration leads to antiandrogenic activity. This activity helps to oppose the effects of naturally occurring androgens, inhibiting the binding of dihydrotestosterone (DHT) to its receptor, and preventing androgen synthesis in the ovaries, helping to treat acne and hirsutism.1,12,19 Drospirenone may also decrease the level of edema in sebaceous follicle during the second half of the menstrual cycle, when acne often appears.19

TargetActionsOrganism
AProgesterone receptor
agonist
Humans
AMineralocorticoid receptor
antagonist
Humans
AAndrogen receptor
antagonist
Humans
UGlucocorticoid receptor
binder
Humans
Additional Data Available
Adverse Effects

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

The absolute bioavailability of drospirenone is approximately 76% due to first-pass effects.13,19 The maximum plasma concentration of drospirenone occurs within 1 to 2 hours after oral administration and is estimated to range between 60 and 87 ng/mL.1 A European prescribing monograph for the combination product of estradiol and drospirenone indicates that drospirenone is both completely and rapidly absorbed. It reports a Cmax of 21.9 ng/ml, achieved approximately 1-hour post-administration. The absolute bioavailability is reported to range between 76 to 85%.23

Volume of distribution

The volume of distribution of drospirenone is estimated to be 4 L/kg, according to the FDA label for Yaz.19 Prescribing information from a combination of estradiol and drospirenone estimates the volume of distribution to range from 3.7- 4.2 L/kg.23

Protein binding

Drospirenone is about 95% to 97% bound to serum plasma protein, likely to albumin.1 During in vitro studies, drospirenone was found to bind with low affinity to sex hormone-binding globulin (SHBG).20 Another reference indicates that drospirenone binds to serum albumin but does not bind to sex hormone-binding globulin (SHBG), nor corticoid binding globulin (CBG). Only 3-5% of the total drospirenone concentration is measured as a free steroid. 23

Metabolism

Drospirenone is heavily metabolized. The two major inactive metabolites identified are the acid form of drospirenone produced by the opening of its lactone ring, known as M11, and the 4,5-dihydro-drospirenone-3-sulfate (M14).1,13 Drospirenone also undergoes oxidative metabolism via the hepatic cytochrome enzyme CYP3A4.17,18,23

Route of elimination

Various metabolites of drospirenone are measured in the urine and feces. Drospirenone elimination from the body is almost after 10 days post-administration1 when negligible amounts of drospirenone are found unchanged in both the urine and feces.23 Between 38% to 47% of the metabolites are identified as glucuronide and sulfate conjugates in the urine. In the feces, approximately 17% to 20% of identifiable metabolites are found to be excreted as glucuronides and sulfates.1

Half life

The serum half-life of drospirenone is estimated to be 30 hours.13 The half-life of drospirenone metabolite excretion in the urine and feces is approximately 40 hours.23

Clearance

Drospirenone is rapidly cleared, typically within 2-3 days of administration of the last active tablet.14 The rate of clearance of drospirenone calculated in the serum ranges from 1.2-1.5 ml/min/kg, however, this value can vary by up to 25% according to the patient.23

Toxicity

The oral LD50 of drospirenone in rats is >2000 mg/kg.22

Overdose information An overdose of drospirenone, like other oral contraceptives, may lead to cause nausea or withdrawal bleeding. For drospirenone in particular, as an analog of spironolactone, may affect the levels of serum sodium and potassium. Their concentrations should be monitored in cases of overdose in addition to monitoring from metabolic acidosis and hyperkalemia, which may also result.15,19

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be decreased when used in combination with Drospirenone.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be decreased when used in combination with Drospirenone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Drospirenone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Drospirenone.
4-OxoretinolThe therapeutic efficacy of Drospirenone can be decreased when used in combination with 4-Oxoretinol.
6-Deoxyerythronolide BThe metabolism of Drospirenone can be decreased when combined with 6-Deoxyerythronolide B.
7-ethyl-10-hydroxycamptothecinThe metabolism of Drospirenone can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
7-NitroindazoleThe metabolism of Drospirenone can be increased when combined with 7-Nitroindazole.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Drospirenone.
AbacavirDrospirenone may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Food reduces the rate of absorption, but not the extent of absorption.

References

Synthesis Reference

DOI: 10.1002/cjoc.201201147

General References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Wichianpitaya J, Taneepanichskul S: A comparative efficacy of low-dose combined oral contraceptives containing desogestrel and drospirenone in premenstrual symptoms. Obstet Gynecol Int. 2013;2013:487143. doi: 10.1155/2013/487143. Epub 2013 Feb 20. [PubMed:23577032]
  3. Larivee N, Suissa S, Khosrow-Khavar F, Tagalakis V, Filion KB: Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies. BJOG. 2017 Sep;124(10):1490-1499. doi: 10.1111/1471-0528.14623. Epub 2017 May 5. [PubMed:28276140]
  4. Oedingen C, Scholz S, Razum O: Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: The role of the progestogen type and estrogen dose. Thromb Res. 2018 May;165:68-78. doi: 10.1016/j.thromres.2018.03.005. Epub 2018 Mar 15. [PubMed:29573722]
  5. Li J, Ren J, Sun W: A comparative systematic review of Yasmin (drospirenone pill) versus standard treatment options for symptoms of polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:13-21. doi: 10.1016/j.ejogrb.2016.11.013. Epub 2016 Nov 16. [PubMed:27923166]
  6. Lopez LM, Kaptein AA, Helmerhorst FM: Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD006586. doi: 10.1002/14651858.CD006586.pub4. [PubMed:22336820]
  7. Authors unspecified: ACOG Committee Opinion Number 540: Risk of venous thromboembolism among users of drospirenone-containing oral contraceptive pills. Obstet Gynecol. 2012 Nov;120(5):1239-42. doi: http://10.1097/AOG.0b013e318277c93b. [PubMed:23090561]
  8. Kluft C, Zimmerman Y, Mawet M, Klipping C, Duijkers IJ, Neuteboom J, Foidart JM, Bennink HC: Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol. Contraception. 2017 Feb;95(2):140-147. doi: 10.1016/j.contraception.2016.08.018. Epub 2016 Sep 1. [PubMed:27593335]
  9. Regidor PA, Schindler AE: Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone. Oncotarget. 2017 Aug 3;8(47):83334-83342. doi: 10.18632/oncotarget.19833. eCollection 2017 Oct 10. [PubMed:29137347]
  10. Momoeda M, Kondo M, Elliesen J, Yasuda M, Yamamoto S, Harada T: Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter, randomized, open-label, active-controlled study. Int J Womens Health. 2017 May 2;9:295-305. doi: 10.2147/IJWH.S134576. eCollection 2017. [PubMed:28496369]
  11. Suvarna Y, Maity N, Kalra P, Shivamurthy MC: Comparison of efficacy of metformin and oral contraceptive combination of ethinyl estradiol and drospirenone in polycystic ovary syndrome. J Turk Ger Gynecol Assoc. 2016 Jan 12;17(1):6-9. doi: 10.5152/jtgga.2016.16129. eCollection 2016. [PubMed:27026772]
  12. Mathur R, Levin O, Azziz R: Use of ethinylestradiol/drospirenone combination in patients with the polycystic ovary syndrome. Ther Clin Risk Manag. 2008 Apr;4(2):487-92. doi: 10.2147/tcrm.s6864. [PubMed:18728832]
  13. Rapkin AJ, Winer SA: Drospirenone: a novel progestin. Expert Opin Pharmacother. 2007 May;8(7):989-99. doi: 10.1517/14656566.8.7.989 . [PubMed:17472544]
  14. Breech LL, Braverman PK: Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder. Int J Womens Health. 2010 Aug 9;1:85-95. [PubMed:21072278]
  15. Bird ST, Pepe SR, Etminan M, Liu X, Brophy JM, Delaney JA: The association between drospirenone and hyperkalemia: a comparative-safety study. BMC Clin Pharmacol. 2011 Dec 30;11:23. doi: 10.1186/1472-6904-11-23. [PubMed:22208934]
  16. Zhang N, Shon J, Kim MJ, Yu C, Zhang L, Huang SM, Lee L, Tran D, Li L: Role of CYP3A in Oral Contraceptives Clearance. Clin Transl Sci. 2018 May;11(3):251-260. doi: 10.1111/cts.12499. Epub 2017 Oct 6. [PubMed:28986954]
  17. Cadeddu G, Deidda A, Stochino ME, Velluti N, Burrai C, Del Zompo M: Clozapine toxicity due to a multiple drug interaction: a case report. J Med Case Rep. 2015 Apr 2;9:77. doi: 10.1186/s13256-015-0547-2. [PubMed:25890012]
  18. Wiesinger H, Berse M, Klein S, Gschwend S, Hochel J, Zollmann FS, Schutt B: Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol. Br J Clin Pharmacol. 2015 Dec;80(6):1399-410. doi: 10.1111/bcp.12745. Epub 2015 Oct 28. [PubMed:26271371]
  19. YAZ fda label [Link]
  20. Yaz Bayer monograph [Link]
  21. 2012 FDA safety statement, YAZ [Link]
  22. FDA pharmacology review, Drospirenone [Link]
  23. Angeliq EU label [Link]
  24. drospirenone/ethinyl estradiol - Drug Summary [Link]
  25. Angeliq FDA label [Link]
  26. Safyral FDA label [Link]
External Links
Human Metabolome Database
HMDB0015467
KEGG Drug
D03917
PubChem Compound
68873
PubChem Substance
46507653
ChemSpider
62105
BindingDB
150275
ChEBI
50838
ChEMBL
CHEMBL1509
Therapeutic Targets Database
DAP001206
PharmGKB
PA164749409
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Drospirenone
ATC Codes
G03AC10 — DrospirenoneG03FA17 — Drospirenone and estrogenG03AA12 — Drospirenone and ethinylestradiol
FDA label
Download (292 KB)
MSDS
Download (567 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingSupportive CareEndometriosis of Uterus1
1CompletedNot AvailableContraception1
1CompletedNot AvailableHealthy Volunteers2
1CompletedBasic ScienceFollicle Count / Follicle Size / Induction of follicle development / Oral Contraception / Ovarian Follicle1
1CompletedOtherBiological Availability1
1CompletedOtherContraception1
1CompletedOtherHealthy Volunteers1
1CompletedPreventionContraception1
1CompletedTreatmentContraception3
1RecruitingBasic ScienceHealthy Volunteers1
1RecruitingOtherHealthy Volunteers1
1TerminatedOtherHuman Immunodeficiency Virus (HIV) Infections1
1TerminatedTreatmentHealthy Volunteers1
1Unknown StatusTreatmentPolycystic Ovaries Syndrome1
1, 2CompletedPreventionContraception / Hemostasis Parameter / Liver Metabolism1
2CompletedPreventionContraception1
2CompletedPreventionContraceptive, Oral, Hormonal1
2CompletedPreventionPrevention of Pregnancy1
2CompletedTreatmentHigh Blood Pressure (Hypertension) / One to five years postmenopausal / Pre-Hypertension1
2TerminatedTreatmentDepression / PMDD / Premenstrual Dysphoric Disorder / Premenstrual Syndrome1
2TerminatedTreatmentHidradenitis Suppurativa (HS)1
2, 3CompletedTreatmentMenstrual Cramps2
3Active Not RecruitingTreatmentContraception1
3CompletedPreventionContraception12
3CompletedPreventionContraception / Neural Tube Defects (NTDs) / Oral Contraception1
3CompletedPreventionContraception / Oral Contraception / Ovulation Inhibition1
3CompletedTreatmentAcne Vulgaris4
3CompletedTreatmentContraception1
3CompletedTreatmentEndometriosis1
3CompletedTreatmentHealthy Volunteers1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / One to five years postmenopausal1
3CompletedTreatmentHot Flushes / Vasomotor Symptoms1
3CompletedTreatmentMenstrual Cramps1
3CompletedTreatmentOral Contraception1
3CompletedTreatmentPolycystic Ovaries Syndrome3
3CompletedTreatmentPremenstrual Dysphoric Disorder ( PMDD)1
3CompletedTreatmentPremenstrual Syndrome1
3CompletedTreatmentVasomotor Symptoms2
3CompletedTreatmentOne to five years postmenopausal1
3RecruitingTreatmentPolycystic Ovaries Syndrome1
3WithdrawnNot AvailableMetrorrhagia1
3WithdrawnTreatmentMenstrual Cramps1
4CompletedNot AvailableBlood Pressures / Contraception1
4CompletedNot AvailableContraception2
4CompletedNot AvailablePolycystic Ovarian Syndrome / Polycystic Ovaries Syndrome1
4CompletedBasic ScienceAdverse Effect of Oral Contraceptives, Subsequent Encounter1
4CompletedDiagnosticJoint Stabilioty1
4CompletedPreventionCardiovascular Heart Disease1
4CompletedTreatmentContraception2
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentPolycystic Ovaries Syndrome3
4CompletedTreatmentPremenstrual Syndrome1
4CompletedTreatmentPrimary Dysmenorrhoea1
4CompletedTreatmentOne to five years postmenopausal1
4Enrolling by InvitationTreatmentWeight Changes1
4RecruitingTreatmentPolycystic Ovaries Syndrome1
4Unknown StatusNot AvailableEndometriotic Cysts / Menstrual Cramps / Painful Intercourse / Pelvic Pain1
4Unknown StatusPreventionHyperandrogenism / Menstrual Irregularities / Polycystic Ovarian Syndrome1
4Unknown StatusTreatmentContraceptive Methods Comparison1
Not AvailableCompletedNot AvailableContraception3
Not AvailableCompletedNot AvailableMetabolic Syndromes / Polycystic Ovaries Syndrome1
Not AvailableCompletedNot AvailablePostmenopausal Osteoporosis (PMO) / Postmenopausal Period1
Not AvailableCompletedTreatmentDepression / Premenstrual Syndrome1
Not AvailableCompletedTreatmentEstro-progestin Drugs / Polycystic Ovaries Syndrome1
Not AvailableCompletedTreatmentOne to five years postmenopausal1
Not AvailableNot Yet RecruitingTreatmentPremature Menopause / Primary Ovarian Insufficiency1
Not AvailableRecruitingNot AvailableInfertility1
Not AvailableUnknown StatusTreatmentEndothelial Dysfunction / Polycystic Ovaries Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral
Tablet, film coatedOral4 mg/1
TabletOral
KitOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6787531No2004-09-072020-08-31Us
US6933395No2005-08-232017-08-11Us
US8906890No2014-12-092031-10-22Us
US6987101No2006-01-172017-12-22Us
US7163931No2007-01-162021-12-20Us
US6958326No2005-10-252021-12-20Us
US5798338No1998-08-252015-07-10Us
US6441168No2002-08-272022-07-30Us
US8617597No2013-12-312030-02-08Us
US10179140No2019-01-152031-06-28Us
US9603860No2011-06-282031-06-28Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)196-200https://www.chemicalbook.com/ChemicalProductProperty_US_CB8695608.aspx
boiling point (°C)552.2https://www.lookchem.com/Drospirenone/
logP3.08https://pdf.hres.ca/dpd_pm/00042999.PDF
logS-5.2http://www.hmdb.ca/metabolites/HMDB0015467
pKa-5http://www.hmdb.ca/metabolites/HMDB0015467
Predicted Properties
PropertyValueSource
Water Solubility0.00225 mg/mLALOGPS
logP2.36ALOGPS
logP3.37ChemAxon
logS-5.2ALOGPS
pKa (Strongest Basic)-5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.37 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity101.68 m3·mol-1ChemAxon
Polarizability41.81 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6376
P-glycoprotein substrateSubstrate0.6524
P-glycoprotein inhibitor IInhibitor0.6171
P-glycoprotein inhibitor IINon-inhibitor0.6726
Renal organic cation transporterNon-inhibitor0.7005
CYP450 2C9 substrateNon-substrate0.796
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6964
CYP450 1A2 substrateNon-inhibitor0.5534
CYP450 2C9 inhibitorNon-inhibitor0.8665
CYP450 2D6 inhibitorNon-inhibitor0.9336
CYP450 2C19 inhibitorNon-inhibitor0.7754
CYP450 3A4 inhibitorNon-inhibitor0.8355
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8541
Ames testNon AMES toxic0.9163
CarcinogenicityNon-carcinogens0.9505
BiodegradationNot ready biodegradable0.9757
Rat acute toxicity1.9430 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9393
hERG inhibition (predictor II)Non-inhibitor0.8215
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (37.1 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as spironolactones and derivatives. These are steroid lactones with a structure based on the spironolactone skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid lactones
Direct Parent
Spironolactones and derivatives
Alternative Parents
Cyclohexenones / Gamma butyrolactones / Tetrahydrofurans / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Spironolactone / Cyclohexenone / Gamma butyrolactone / Tetrahydrofuran / Cyclic ketone / Lactone / Ketone / Carboxylic acid ester / Oxacycle / Organoheterocyclic compound
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
3-oxo steroid, 3-oxo Delta(4)-steroid, steroid lactone (CHEBI:50838)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Bray JD, Jelinsky S, Ghatge R, Bray JA, Tunkey C, Saraf K, Jacobsen BM, Richer JK, Brown EL, Winneker RC, Horwitz KB, Lyttle CR: Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells. J Steroid Biochem Mol Biol. 2005 Dec;97(4):328-41. Epub 2005 Sep 12. [PubMed:16157482]
  3. Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH: The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception. 1996 Oct;54(4):243-51. [PubMed:8922878]
  4. Arias-Loza PA, Hu K, Schafer A, Bauersachs J, Quaschning T, Galle J, Jazbutyte V, Neyses L, Ertl G, Fritzemeier KH, Hegele-Hartung C, Pelzer T: Medroxyprogesterone acetate but not drospirenone ablates the protective function of 17 beta-estradiol in aldosterone salt-treated rats. Hypertension. 2006 Nov;48(5):994-1001. Epub 2006 Sep 25. [PubMed:17000933]
  5. Sitruk-Ware R: New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. Epub 2005 Nov 16. [PubMed:16291771]
  6. Sitruk-Ware R: New progestogens: a review of their effects in perimenopausal and postmenopausal women. Drugs Aging. 2004;21(13):865-83. [PubMed:15493951]
  7. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [PubMed:7625729]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH: The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception. 1996 Oct;54(4):243-51. [PubMed:8922878]
  3. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [PubMed:7625729]
  4. Oelkers WK: Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids. 1996 Apr;61(4):166-71. [PubMed:8732994]
  5. Oelkers W: Antimineralocorticoid activity of a novel oral contraceptive containing drospirenone, a unique progestogen resembling natural progesterone. Eur J Contracept Reprod Health Care. 2002 Dec;7 Suppl 3:19-26; discussion 42-3. [PubMed:12659403]
  6. Oelkers W: Drospirenone, a progestogen with antimineralocorticoid properties: a short review. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):255-61. doi: 10.1016/j.mce.2003.10.030. [PubMed:15134826]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Curator comments
References indicate a lower affinity to the androgen receptor.
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [PubMed:7625729]
  3. Oelkers W: Drospirenone, a progestogen with antimineralocorticoid properties: a short review. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):255-61. doi: 10.1016/j.mce.2003.10.030. [PubMed:15134826]
  4. Yaz Bayer monograph [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Curator comments
References indicate a weak binding affinity to the glucocorticoid receptor.
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception. 2000 Jul;62(1):29-38. [PubMed:11024226]
  2. Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci. 1995 Jun 12;761:311-35. doi: 10.1111/j.1749-6632.1995.tb31386.x. [PubMed:7625729]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Amenorrheic patients on drospirenone were found to exhibit inhibition of COX-2 expression. Those with breakthrough bleeding on drospirenone were found to have increased COX-2 expression.
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Maia H Jr, Casoy J, Athayde C, Valente Filho J, Coutinho EM: The effect of a continuous regimen of drospirenone 3 mg/ethinylestradiol 30 microg on Cox-2 and Ki-67 expression in the endometrium. Eur J Contracept Reprod Health Care. 2010 Feb;15(1):35-40. doi: 10.3109/13625180903383928. [PubMed:20063991]
  2. Maia H Jr, Haddad C, Pinheiro N, Casoy J: The effect of oral contraceptives on aromatase and Cox-2 expression in the endometrium of patients with idiopathic menorrhagia or adenomyosis. Int J Womens Health. 2013 Jun 13;5:293-9. doi: 10.2147/IJWH.S45093. Print 2013. [PubMed:23788841]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
This enzyme activity is based on the results of an in vivo study with rat and dog subjects.
General Function
Protein homodimerization activity
Specific Function
Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxyl...
Gene Name
PON1
Uniprot ID
P27169
Uniprot Name
Serum paraoxonase/arylesterase 1
Molecular Weight
39730.99 Da
References
  1. Koitka M, Hochel J, Gieschen H, Borchert HH: Improving the ex vivo stability of drug ester compounds in rat and dog serum: inhibition of the specific esterases and implications on their identity. J Pharm Biomed Anal. 2010 Feb 5;51(3):664-78. doi: 10.1016/j.jpba.2009.09.023. Epub 2009 Sep 23. [PubMed:19850433]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wiesinger H, Berse M, Klein S, Gschwend S, Hochel J, Zollmann FS, Schutt B: Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol. Br J Clin Pharmacol. 2015 Dec;80(6):1399-410. doi: 10.1111/bcp.12745. Epub 2015 Oct 28. [PubMed:26271371]
  2. Cadeddu G, Deidda A, Stochino ME, Velluti N, Burrai C, Del Zompo M: Clozapine toxicity due to a multiple drug interaction: a case report. J Med Case Rep. 2015 Apr 2;9:77. doi: 10.1186/s13256-015-0547-2. [PubMed:25890012]
  3. Zhang N, Shon J, Kim MJ, Yu C, Zhang L, Huang SM, Lee L, Tran D, Li L: Role of CYP3A in Oral Contraceptives Clearance. Clin Transl Sci. 2018 May;11(3):251-260. doi: 10.1111/cts.12499. Epub 2017 Oct 6. [PubMed:28986954]
  4. Angeliq EU label [Link]

Drug created on July 08, 2007 11:03 / Updated on December 02, 2019 05:49