Comparative pharmacokinetic estimates of drospirenone alone and in combination with ethinyl estradiol after single and repeated oral administration in healthy females

The European Journal of Contraception & Reproductive Health

et al. 2020

Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications. Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties. Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h. Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake. ARTICLE HISTORY

Section: Preclinical Datamentioning

confidence: 89%

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature

Palacios

Regidor²,

The European Journal of Contraception & Reproductive Health

et al. 2020

“…DRSP exhibits a different pharmacokinetic profile when administered together with ethynyl estradiol. While the new formulation with 4 mg DRSP contains 33% more active ingredient than a reference combined oral contraceptive (3 mg DRSP + 0•02 mg ethinylestradiol), the extent of systemic exposure at steady-state is using dose corrected data about 33% less with the new formulation, without dose correction (AUC 0-24h , ss GMR = 77•81, 90% CI = 74•64% -81•12%) [17]. Combined with a reduced C max , this pharmacokinetic profile of the new formulation may be relevant for similar efficacy and enhanced safety, both characteristics explaining the high efficacy and safety profile found in these clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime

Palacios

Regidor³

2020

BMC Women's Health

Background A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks. Methods Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. Results No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed. Conclusions The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors. Trial registration EudraCT registration numbers: 2010–021787-15 & 2011–002396-42. Clincaltrials.gov: NCT02269241.

“…The total exposure to drospirenone is statistically significantly lower for drospirenone alone, even though the individual strength in the tablet formulations is higher (4 mg vs 3 mg). 9 This study investigated the transfer of drospirenone to breast milk following a repeated oral administration of the new estrogen-free contraceptive containing 4 mg drospirenone. The PK parameters of drospirenone in serum and in breast milk were in a similar range to previous single oral dose studies of 3 mg DRSP + 30 µg EE and indicate that lactation does not influence the PKs of the drug.…”

Section: Discussionmentioning

confidence: 99%

A single-arm study to evaluate the transfer of drospirenone to breast milk after reaching steady state, following oral administration of 4 mg drospirenone in healthy lactating female volunteers

Melka¹,

Kask²,

Womens Health (Lond Engl)

et al. 2020

Objective: The primary objective of this trial was to assess the transfer of drospirenone to breast milk after daily administration of an oral test preparation containing 4 mg of drospirenone at the steady state. The secondary objective of the trial was to assess safety based on clinical and laboratory measurements and reporting of adverse events and/or adverse drug reactions. Patients and Methods: This was an open label, non-comparative single-center study. Drospirenone 4 mg per day was the first postpartum contraceptive for the study participants who were no longer breastfeeding yet were still lactating. It was administered for 7 days to achieve steady-state concentration. All participants were volunteers who planned to use oral contraceptives as their family planning method in the future. Results: Twelve volunteers completed the trial according to the protocol, and the samples of all 12 study completers were analyzed. The average concentration–time curve of drospirenone in plasma 24 h after the administration of the last dose (area under the curve (0–24 h)) was 635.33 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0–120 h)) was 1180.57 ng h/mL, respectively. The average Cmax was 48.64 ng/mL. The average concentration–time curve of drospirenone in milk 24 h after the administration of the last dose (area under the curve (0–24 h)) was 134.35 ng h/mL and 120 h after the single repeated dose administration (area under the curve (0–120 h)) was 227.17 ng h/mL, respectively. The average Cmax was 10.34 ng/mL. Conclusion: On average, 18.13% of plasma drospirenone made it to breast milk and the highest concentration of drospirenone in breast milk was 17.55% of that in plasma. The total quantity of drospirenone passing to breast milk is on average 4478 ng during a 24-h period representing 0.11% of the maternal daily dose. Thus, at the recommended doses, no effects on breastfed newborns/infants are anticipated with drospirenone 4 mg.