Volnea
VOLNEA- desogestrel and ethinyl estradiol
Xiromed, LLC.
Rx only
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs, including Volnea, are contraindicated in women who are over 35 years of age and smoke (see CONTRAINDICATIONS and WARNINGS).
DESCRIPTION
Volnea (desogestrel and ethinyl estradiol tablets, USP and ethinyl estradiol tablets, USP) provides an oral contraceptive regimen of 21 white round tablets each containing 0.15 mg desogestrel (13-ethyl-11- methylene-18,19-dinor-17 alpha-pregn- 4-en- 20-yn-17-ol), 0.02 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17-diol), and inactive ingredients which include alpha-tocopherol, colloidal silicon dioxide, aquarius cool vanilla (contains hypromellose 2910, polyethylene glycol and titanium dioxide), corn starch, lactose monohydrate, povidone, and stearic acid, followed by 2 inert green round tablets contain the following inactive ingredients: aquarius cottage green (contains FD&C blue no. 2 aluminum lake, hypromellose 2910, polysorbate 80, titanium dioxide, triacetin, and yellow iron oxide), colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate and povidone.
Volnea also contains 5 yellow round tablets containing 0.01 mg ethinyl estradiol (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17-diol) and inactive ingredients which include lactose monohydrate, microcrystalline cellulose, magnesium stearate, and opadry yellow (contains lecithin, polyvinyl alcohol, talc, titanium dioxide, xanthan gum, and yellow iron oxide). The molecular weights for desogestrel and ethinyl estradiol are 310.48 and 296.40 respectively. The structural formulas are as follows:
CLINICAL PHARMACOLOGY
Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).
Receptor binding studies, as well as studies in animals, have shown that etonogestrel, the biologically active metabolite of desogestrel, combines high progestational activity with minimal intrinsic androgenicity (91, 92). The relevance of this latter finding in humans is unknown.
Pharmacokinetics
Absorption
Desogestrel is rapidly and almost completely absorbed and converted into etonogestrel, its biologically active metabolite. Following oral administration, the relative bioavailability of desogestrel compared to a solution, as measured by serum levels of etonogestrel, is approximately 100%. Desogestrel/ethinyl estradiol and ethinyl estradiol tablets provide two different regimens of ethinyl estradiol; 0.02 mg in the combination tablet [white] as well as 0.01 mg in the yellow tablet. Ethinyl estradiol is rapidly and almost completely absorbed. After a single dose of desogestrel/ethinyl estradiol and ethinyl estradiol combination tablet [white], the relative bioavailability of ethinyl estradiol is approximately 93% while the relative bioavailability of the 0.01 mg tablet [yellow] is 99%. The effect of food on the bioavailability of desogestrel/ethinyl estradiol and ethinyl estradiol tablets following oral administration has not been evaluated.
The pharmacokinetics of etonogestrel and ethinyl estradiol following multiple dose administration of desogestrel/ethinyl estradiol and ethinyl estradiol tablets were determined during the third cycle in 17 subjects. Plasma concentrations of etonogestrel and ethinyl estradiol reached steady-state by Day 21. The AUC(0–24) for etonogestrel at steady-state on Day 21 was approximately 2.2 times higher than AUC(0–24) on Day 1 of the third cycle. The pharmacokinetic parameters of etonogestrel and ethinyl estradiol during the third cycle following multiple dose administration of desogestrel/ethinyl estradiol and ethinyl estradiol tablets are summarized in Table 1.
TABLE 1: MEAN (SD) PHARMACOKINETIC PARAMETERS OF DESOGESTREL/ETHINYL ESTRADIOL AND ETHINYL ESTRADIOL OVER A 28-DAY DOSING PERIOD IN THE THIRD CYCLE (n=17).
| Etonogestrel | ||||||
| Day | Dosea) mg | Cmax pg/mL | Tmax h | t1/2 h | AUC0–24 pg/mL•hr | CL/F L/h |
| 1 | 0.15 | 2503.6 (987.6) | 2.4 (1) | 29.8 (16.3) | 17,832 (5674) | 5.4 (2.5) |
| 21 | 0.15 | 4091.2 (1186.2) | 1.6 (0.7) | 27.8 (7.2) | 39,391 (12,134) | 4.4 (1.4) |
| a) Desogestrel | ||||||
| Ethinyl Estradiol | ||||||
| Day | Dose mg | Cmax pg/mL | Tmax h | t1/2 h | AUC0–24 pg/mL•hr | CL/F L/h |
| 1 | 0.02 | 51.9 (15.4) | 2.9 (1.2) | 16.5 (4.8) | 566 (173)a) | 25.7 (9.1) |
| 21 | 0.02 | 62.2 (25.9) | 2 (0.8) | 23.9 (25.5) | 597 (127)a) | 35.1 (8.2) |
| 24 | 0.01 | 24.6 (10.8) | 2.4 (1) | 18.8 (10.3) | 246 (65) | 43.6 (12.2) |
| 28 | 0.01 | 35.3 (27.5) | 2.1 (1.3) | 18.9 (8.3) | 312 (62) | 33.2 (6.6) |
| Cmax – measured peak concentration | ||||||
| Tmax – observed time of peak concentration | ||||||
| t1/2 – elimination half-life, calculated by 0.693/Kelim | ||||||
| AUC0–24 – area under the concentration-time curve calculated by the linear trapezoidal rule (Time 0 to 24 hours) | ||||||
| CL/F – apparent clearance | ||||||
| a) n=16 | ||||||
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