DROSPIRONONE is a progestin medication used for birth control pills prevent pregnancy & pcos etc....

1. Drospironone
Name: Jayaprakash Lenka
Regd. No: 2161613002
M.Pharm. in Pharmacology 2nd Sem
Guided by: Prof.(Dr.) Pratap Kumar Sahu
Professor, Dept of Pharmacology, School of Pharmaceutical Sciences,
Siksha “O” Anusandhan University, Bhubaneswar

2. INTRODUCTION TO DRUG:
 Drospirenone is a progestin medication which is used in birth control pills to
prevent pregnancy and in menopausal hormone therapy & PCOS etc.
 It is available both alone under the brand name Drospert 4mg ( Torrent
Pharmaceuticals) and in combination with an estrogen under the brand
name Yamini (Lupin Pharmaceuticals) & Dronis 30 ( Sun
Pharmaceuticals.) among others.
 The medication is taken in Oral route of drug administration.
 Drospirenone was patented in 1976 and introduced for medical use in 2000.
 The medication is sometimes referred to as a "fourth-generation" progestin.
 Available dosage: Drospironone = 3mg and Ethinyl Estradiol = 0.03mg OD after
food for 21 days Oral.

3. Classification of Progestin and Estrogen:
Progestin:
 Progesterone derivatives: Medroxy
progesterone acetate.
 Nor testosterone derivatives:
1. Estranes: Norethisterone.
2. Gonanes: Levonorgestrel.
 Anti Progestins: Mifepristone.
 Anti Androgens: Drospironone.
 Selective progesterone receptor
modulator: Ulipristal.
Estrogen
 Natural Estrogens: Estradiol, Estriol.
 Synthetic Estrogens:
1. Steroidal: Ethinyl Estradiol
2. Non-Steroidal: Dienestrol.
 Anti Estrogens: Clomiphene citrate.
 Selective estrogen receptor down regulator:
Fulvestrant.
 Selective estrogen receptor modulator:
Tamoxifen citrate.
 Aromatase Inhibitors: Letrozole

4. MOA Of Drospironone:
 Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing
pregnancy.
 When combined with ethinyl estradiol, it has been shown to have favorable effects
on the plasma lipid profile.
 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.
 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.

5.  Drospirenone is an analog of the diuretic spironolactone,
which exerts anti-mineralocorticoid activity, blocking
aldosterone receptors, which increases sodium and water
excretion.
 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 (abnormal growth of hair on a woman's face and
body).
 Drospirenone may also decrease the level of edema in
sebaceous follicle during the second half of the menstrual
cycle, when acne often appears. Structure of Drospironone

6. Mineralocorticoid receptor antagonist
Androgen receptor antagonist
Progesterone receptor agonist
Glucocorticoid receptor agonist

7. Therapeutic Use of Drospironone in Polycystic
Ovary Syndrome:
 Polycystic ovary syndrome (PCOS) is one of the most common
endocrine/metabolic disorders found in women, affecting approximately 105
million women worldwide.
 It is characterized by ovulatory dysfunction, often presenting as oligomenorrhea
or menorrhea and either clinical or biochemical hyperandrogenism.
 It can lead the possibility of infertility and many hormonal related disease in
women.
 Diet and lifestyle have an essential role to improve PCOS in younger girls.
 Combined oral contraceptive (COC) therapy has long been a great benefit over
care for women with PCOS.
 COC therapy often provides clinical improvement in the areas of excessive hair
growth, unpredictable periods, acne, and weight gain.

8.  One of the main issues in COC therapy is choosing the most appropriate progestin
component to provide the greatest anti androgenic effects.
 Drospirenone, a relatively new progestin, has shown benefit in the PCOS
population when used in conjunction with ethinyl estradiol.
 Drospirenone differs from other progestins currently available in other COC
compounds, as it exhibits both mineralocorticoid effects and antiandrogenic
effects.
 Part of the novel nature of drospirenone stems from it being structurally and
functionally analogous to spironolactone.
 Spironolactone is an aldosterone antagonist, and a potassium-sparing diuretic.
Because of this structural and functional similarity with spironolactone,
drospirenone also exhibits anti-mineralocorticoid activity.
 This property counteracts the estrogen stimulated activity of the renin angiotensin-
aldosterone system, which can influence the regulation of water and electrolyte
balance. so, it can clear all the edema occurs during PCOS and successfully
treated PCOS.

9. Pharmacokinetics:
 Absorption: The absolute bioavailability of drospirenone is approximately 76% due to first-pass
effects. 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.
 Volume of distribution: combination of estradiol and drospirenone estimates the volume of
distribution to range from 3.7- 4.2 L/kg.
 Protein binding: Drospirenone is about 95% to 97% bound to serum plasma protein, likely to
albumin.
 Metabolism: Drospirenone undergoes oxidative metabolism via the hepatic cytochrome enzyme
CYP3A4.
 Excretion: Various metabolites of drospirenone are excreted through urine and feces.
Drospirenone elimination from the body is almost after 10 days post-administration
 Half-life: The serum half-life of drospirenone is estimated to be 30 hours. The half-life of
drospirenone metabolite excretion in the urine and feces is approximately 40 hours.

10. Adverse Effect:
 Adverse effects of drospirenone alone occurring in more than 1% of women may include:
 unscheduled menstrual bleeding (breakthrough or intracyclic) (40.3–64.4%), acne (3.8%)
 metrorrhagia (2.8%)
 headache (2.7%)
 breast pain (2.2%)
 weight gain (1.9%)
 dysmenorrhea (1.9%)
 nausea (1.8%)
 vaginal hemorrhage (1.7%)
 decreased libido (1.3%)
 breast tenderness (1.2%) and irregular menstruation (1.2%).
 Along with other side effects like change in appetite, less interest in sexual desire, depressed mood or mood
swings etc.

11. Drug-Drug Interaction:
 Inhibitors and inducers of the cytochrome P450 enzyme CYP3A4 may influence the levels
and efficacy of drospirenone.
 Treatment for 10 days with 200 mg twice daily ketoconazole, a strong CYP3A4 inhibitor
among other actions, has been found to result in a moderate 2.0- to 2.7-fold increase in
exposure to drospirenone.
 Drospirenone does not appear to influence the metabolism of omeprazole (metabolized
via CYP2C19), simvastatin (metabolized via CYP3A4), or midazolam (metabolized via
CYP3A4), and likely does not influence the metabolism of other medications that are
metabolized via these pathways.
 Drospirenone may interact with potassium-sparing medications such as ACE
inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, potassium
supplements, heparin, ant mineralocorticoids, and nonsteroidal anti-inflammatory drugs to
further increase potassium levels.
 This may increase the risk of hyperkalemia (high potassium levels).

12. Uses:
 This medication is a combination of 2 hormones: an estrogen (ethinyl estradiol) and
a progestin (drospirenone).
 This can be used to prevent pregnancy.
 This medication also may be used to treat premenstrual dysphoric disorder (PMDD) or
moderate acne if you have chosen to use birth control pills as your method of pregnancy
prevention.
 Besides preventing pregnancy, birth control pills may make your periods more regular,
decrease blood loss and painful periods, and decrease your risk of ovarian cysts.
 It also can be used to treat acne and hirsutism (abnormal growth of hair on a woman's face and
body).
 Using this medication does not protect you or your partner against sexually transmitted
diseases such as HIV, gonorrhea etc.

13. REFERENCE:
 Krattenmacher R: Drospirenone: pharmacology and pharmacokinetics of a unique
progestogen. Contraception. 2000 Jul;62(1):29-38.
 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.
 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.
 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.