Pharmacology Update: Drospirenone and Estradiol Tablets (Angeliq®)
Pharmacology Update
Drospirenone and Estradiol Tablets (Angeliq®)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Associate Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
A new combination hormone product has been approved for the treatment of menopausal symptoms. Drospirenone (DRSP), a progestin with mineralo-corticoid activity, is combined with estradiol (E2). DRSP is the same progestin found in the popular oral contraceptive, Yasmin®. DRSP-E2 is marketed by Berlex as Angeliq®.
Indications
DRSP-E2 is indicated for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. It is also indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause.1
Dosage
The recommended dose is one tablet daily. Each tablet contains 0.5 of drospirenone and 1 mg of 17-β estradiol.
Potential Advantages
Drospirenone differs from other progestins, such as medroxyprogesterone, in that is has mineralocorticoid activity, no androgenic activity, and partial antiandrogen activity.2,3 These properties would suggest that it is less likely to cause water retention, hair growth, and unfavorable lipid changes. Drospirenone in combination with estradiol has also been shown to reduce blood pressure.4,5
Potential Disadvantages
Drospirenone is a weaker progestin in terms of endometrial suppression.2 As a spironolactone analog, drospirenone has the potential to increase serum potassium.1 DRSP should be avoided in patients predisposed to hyperkalemia (eg, renal insufficiency) and should be used with caution in those taking other medication that may increase serum potassium (eg, ACE inhibitors, potassium sparing diuretics).
Comments
Drospirenone is a synthetic progestin that is a spironolactone analog and most closely resembles the pharmacologic properties of natural progesterone.2 Its mineralocorticoid activity is greater than that of spironolactone and progesterone. In addition, drospirenone does not have any androgenic activity but rather partial antiandrogenic activity.2 Support for the indication of treatment of vasomotor symptoms involved demonstrating bioequivalence of the estradiol component of DRSP-E2 to a currently marketed product (Estrace®).1 Regimens containing 1, 2, or 3 mg of DRSP with 1 mg of estradiol showed significant reduction of the frequency of hot flushes and increase bone mineral density.6,7 At 3 mg of DRSP with estradiol, blood pressure was significantly reduced compared to placebo in hypertensive subjects.4,5 In one study (n = 230) mean BP reductions were -8.6/-5.8 mm Hg in patients with hypertension treated with an ACE inhibitor or angiotensin II receptor antagonist vs -3.7 /-2.9 for placebo.4 No significant changes in serum potassium were observed. In another study (n = 213) mean BP reductions were -14.1/-7.9 mm Hg compared to -7.1/-4.3 in patients with stage 1 hypertension.5 Endometrial thickness has been shown to increase by 0.7 mm when estradiol was combined with 1 mg of DRSP, while no change was observed at doses of 2 mg and 3 mg.7 However hyperplasia has not been reported.1,7 The adverse events of DRSP-E2 appeared to be similar to E2 alone.1 The cost of DRSP-E2 was not available at the time of this review.
Clinical Implications
Based on the findings from the Women’s Health Initiative, the use of estrogen with or without a progestin should be used at the lowest dose and shortest duration. Systemic therapy is not first-line treatment for vulvar and vaginal symptoms.1 It is not known whether drospirenone’s pharmacologic properties offer any advantage over other progestins such as medroxyprogesterone. Also the dose of DRSP in Angeliq® is 0.5 mg while studies demonstrating lower BP used 3 mg which roughly corresponds to 25 mg of spironolactone. It is also unclear whether the 0.5 mg dose is sufficient to oppose the estrogen effect on the endometrium or provide any benefit in terms of blood pressure reduction. This product offers a unique new progestin estrogen combination with potential advantages although long-term safety and benefit are yet to be established.
References
1. Angeliq® Product Information. Berlex. September 2005.
2. Sitruk-Ware. Pharmacology of different progestogens: the special case of drospirenone. Climacteric. 2005; 8(Suppl 3):4-12.
3. Sitruk-Ware. New progestogens: a review of their effects in perimenopausal and postmenopausal women. Drugs Aging. 2004;21:865-883.
4. Preston RA, et al. Effects of drospirenone/17-beta estradiol on blood pressure and potassium balance in hypertensive postmenopausal women. Am J Hypertens. 2005;18:797-804.
5. White WB, et al. Antihypertensive effects of drospirenone with 17beta-estradiol, a novel hormone treatment in postmenopausal women with stage 1 hypertension. Circulation. 2005;112:1979-1984.
6. Schurmann R, et al. Estradiol and drospirenone for climacteric symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled study of the safety and efficacy of three dose regimens. Climacteric. 2004;7:189-196.
7. Warming L, et al. Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis. Climacteric. 2004;7:103-111.
A new combination hormone product has been approved for the treatment of menopausal symptoms. Drospirenone (DRSP), a progestin with mineralo-corticoid activity, is combined with estradiol (E2). DRSP is the same progestin found in the popular oral contraceptive, Yasmin®. DRSP-E2 is marketed by Berlex as Angeliq®.Subscribe Now for Access
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