KARIVA (Physicians Total Care, Inc.): FDA Package Insert (2024)

KARIVA — desogestrel/ethinyl estradiol and ethinyl estradiol
Physicians Total Care, Inc.

Rx only

Iss. 12/200911001578

PATIENTS SHOULD BE COUNSELED THAT THIS PRODUCT DOES NOT PROTECT AGAINST HIV INFECTION (AIDS) AND OTHER SEXUALLY TRANSMITTED DISEASES.

DESCRIPTION

Kariva^® (desogestrel/ethinyl estradiol and ethinyl estradiol) Tablets provide 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 colloidal silicon dioxide, hypromellose, lactose monohydrate, polyethylene glycol, povidone, pregelatinized starch, stearic acid and vitamin E, followed by 2 inert light-green round tablets with the following inactive ingredients: FD&C Blue No. 1 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized starch. Kariva^® also contains 5 light-blue 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 colloidal silicon dioxide, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, hypromellose, lactose monohydrate, polydextrose, polyethylene glycol, povidone, pregelatinized starch, stearic acid, titanium dioxide, triacetin and vitamin E. The molecular weight for desogestrel and ethinyl estradiol are 310.48 and 296.40 respectively. The structural formulas are as follows:

DESOGESTREL M.W. 310.48 MF: C₂₂ H₃₀ O

ETHINYL ESTRADIOL M.W. 296.40 MF: C₂₀ H₂₄ O₂

The 21 white tablets meet USP Dissolution Test 2.

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.

Pharmaco*kinetics

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%. Kariva^® (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 light-blue tablet. Ethinyl estradiol is rapidly and almost completely absorbed. After a single dose of Kariva^® combination tablet [white], the relative bioavailability of ethinyl estradiol is approximately 93% while the relative bioavailability of the 0.01 mg tablet [light-blue] is 99%. The effect of food on the bioavailability of Kariva^® Tablets following oral administration has not been evaluated.

The pharmaco*kinetics of etonogestrel and ethinyl estradiol following multiple dose administration of Kariva^® was 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 pharmaco*kinetic parameters of etonogestrel and ethinyl estradiol during the third cycle following multiple dose administration of Kariva^® are summarized in Table I.