Drospirenone
Encyclopedia
Drospirenone is an anti-androgenic synthetic progestin
that is typically used in birth control
. There have been concerns raised regarding its safety and is thus not recommended as a first line agent.
. In combination with ethinyl estradiol it is used as contraception
, to treat moderate acne
, and for premenstrual dysphoric disorder
. In combination with estradiol
it is used to treat menopausal symptoms
and premenstrual dysphoric disorder.
.
Drospirenone can potentially cause hyperkalemia
in high-risk patients, is comparable to a 25 mg dose of spironolactone
.
The medication is contraindicated in people with hepatic dysfunction
, renal insufficiency, adrenal insufficiency
, or in whom the use of oral contraceptives is contraindicated, such as smokers and patients with a history of DVT, stroke
, or other blood clots. Because of the anti-mineralocorticoid effects care needs to be exercised when other drugs that may increase potassium levels are taken. Such medications include ACE inhibitor
s, angiotensin-II receptor agonists, potassium-sparing diuretic
s, potassium supplementation, heparin
, aldosterone antagonist
s, and NSAID
s.
. It is bound not by sex hormone-binding globulin or corticosteroid binding globulin, but by other serum proteins. Metabolites have not been shown to be biologically active, show up in urine and feces, and are essentially completely excreted within 10 days.
The compound differs from other synthetic progestins in that its pharmacological profile in preclinical studies shows it to be closer to the natural progesterone
. As such it has anti-mineralocorticoid
properties, counteracts the estrogen
-stimulated activity of the renin-angiotensin
-aldosterone
system, and is not androgen
ic.
The anti-aldosterone properties exhibited by drospirenone promote sodium excretion and prevent water retention.
to spironolactone
, with a molecular weight of 366.5 and the molecular formula C24H30O3.
:
It has also been formulated in medication to manage menopausal
symptoms using and 1 mg estradiol
per day by oral application. This medication was introduced in the United States in 2007 as Angeliq.
On October 8, 2009, Bayer disclosed that 129 lawsuits had been brought against them over the side effects and marketing of Yaz and Yasmin. The allegations include (but are not limited to):
In September 2009, the FDA cited Bayer for sending out potentially low-quality batches of drosperinone. Bayer justified the shipments by explaining that they monitor the "average" quality of all shipments, not the quality of each individual batch.
In October 2011 the CBC
TV program Market Place
ran a segment discussing issues involved with the usage of Yaz/Yasmin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
that is typically used in birth control
Birth control
Birth control is an umbrella term for several techniques and methods used to prevent fertilization or to interrupt pregnancy at various stages. Birth control techniques and methods include contraception , contragestion and abortion...
. There have been concerns raised regarding its safety and is thus not recommended as a first line agent.
Medical uses
Drospirenone is part of some birth control pills and hormone replacement therapyHormone replacement therapy
Hormone replacement therapy may refer to:*Hormone replacement therapy *Hormone replacement therapy *Hormone replacement therapy *Androgen replacement therapy -See also:...
. In combination with ethinyl estradiol it is used as contraception
Contraception
Contraception is the prevention of the fusion of gametes during or after sexual activity. The term contraception is a contraction of contra, which means against, and the word conception, meaning fertilization...
, to treat moderate acne
Acne vulgaris
Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...
, and for premenstrual dysphoric disorder
Premenstrual dysphoric disorder
Premenstrual dysphoric disorder is a severe form of premenstrual syndrome, afflicting 3% to 8% of women. It is a diagnosis associated primarily with the luteal phase of the menstrual cycle...
. In combination with estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
it is used to treat menopausal symptoms
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
and premenstrual dysphoric disorder.
Adverse effects
Women who take contraceptive pills containing drospirenone have a six- to sevenfold risk of developing thromboembolism compared to women who do not take any contraceptive pill, and twice the risk of women who take a contraceptive pill containing levonorgestrelLevonorgestrel
Levonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
.
Drospirenone can potentially cause hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
in high-risk patients, is comparable to a 25 mg dose of spironolactone
Spironolactone
Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
.
The medication is contraindicated in people with hepatic dysfunction
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
, renal insufficiency, adrenal insufficiency
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
, or in whom the use of oral contraceptives is contraindicated, such as smokers and patients with a history of DVT, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, or other blood clots. Because of the anti-mineralocorticoid effects care needs to be exercised when other drugs that may increase potassium levels are taken. Such medications include ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
s, angiotensin-II receptor agonists, potassium-sparing diuretic
Potassium-sparing diuretic
Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure....
s, potassium supplementation, heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
, aldosterone antagonist
Aldosterone antagonist
Aldosterone antagonist refers to diuretic drugs which antagonize the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure...
s, and NSAID
Non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s.
Mechanism of action
Drospirenone is taken orally with about 76% bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
. It is bound not by sex hormone-binding globulin or corticosteroid binding globulin, but by other serum proteins. Metabolites have not been shown to be biologically active, show up in urine and feces, and are essentially completely excreted within 10 days.
The compound differs from other synthetic progestins in that its pharmacological profile in preclinical studies shows it to be closer to the natural progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
. As such it has anti-mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
properties, counteracts the estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
-stimulated activity of the renin-angiotensin
Renin-angiotensin system
The renin-angiotensin system or the renin-angiotensin-aldosterone system is a hormone system that regulates blood pressure and water balance....
-aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
system, and is not androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
ic.
The anti-aldosterone properties exhibited by drospirenone promote sodium excretion and prevent water retention.
Chemistry
It is an analogAnalog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
to spironolactone
Spironolactone
Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
, with a molecular weight of 366.5 and the molecular formula C24H30O3.
Formulations
The compound is part of certain newer oral contraceptive formulationsOral contraceptive formulations
Oral contraceptives come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogen and synthetic progestogens , and progestogen only pills...
:
- Yasmin contains 3 mg drospirenone and 30 mcg ethinylestradiolEthinylestradiolEthynylestradiol , also ethynyl estradiol , is a derivative of estradiol. Ethynyl estradiol is an orally bio-active estrogen used in almost all modern formulations of combined oral contraceptive pills...
per tablet. It is indicated for the prevention of pregnancy in women who elect an oral contraceptive. - Yasminelle contains 3 mg drospirenone and 20 mcg ethinylestradiol per tablet and is used for contraception.
- Yaz contains 3 mg drospirenone and 20 mcg ethinylestradiol per tablet and is given for 24/4 days with the same indications.
It has also been formulated in medication to manage menopausal
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
symptoms using and 1 mg estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
per day by oral application. This medication was introduced in the United States in 2007 as Angeliq.
Litigation
In 2008, a series of television commercials prompted the FDA to cite Bayer for overstating the approved uses of Yaz while failing to adequately address the risks of the drug. Bayer was required to dispel the inaccurate information contained in those ads by creating new ads that clarified the drug's approved uses.On October 8, 2009, Bayer disclosed that 129 lawsuits had been brought against them over the side effects and marketing of Yaz and Yasmin. The allegations include (but are not limited to):
- Glossing over risks associated with the products and overstating their approved uses in an effort to mislead users of Yaz and Yasmin into believing that the drugs were safe.
- Failure to properly research the medication.
- Failing to recall the drug after post-marketing reports demonstrated that the risk of potentially life-threatening side effects of Yasmin and Yaz outweighed potential benefits that could be achieved via other available oral contraceptives.
In September 2009, the FDA cited Bayer for sending out potentially low-quality batches of drosperinone. Bayer justified the shipments by explaining that they monitor the "average" quality of all shipments, not the quality of each individual batch.
In October 2011 the CBC
Canadian Broadcasting Corporation
The Canadian Broadcasting Corporation, commonly known as CBC and officially as CBC/Radio-Canada, is a Canadian crown corporation that serves as the national public radio and television broadcaster...
TV program Market Place
Market Place
Market Place is the financial programme broadcast Monday to Friday at 10:30pm in Hong Kong by television channel TVB Pearl....
ran a segment discussing issues involved with the usage of Yaz/Yasmin
See also
- Progestins
- Combined oral contraceptive pill
- Oral contraceptive formulationsOral contraceptive formulationsOral contraceptives come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogen and synthetic progestogens , and progestogen only pills...
- Hormone replacement therapyHormone replacement therapy (menopause)Hormone replacement therapy is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women...