active substances: ethinyl estradiol, levonorgestrel;
1 film-coated tablet contains: ethinyl estradiol 0.03 mg, levonorgestrel 0.15 mg;
Excipients: lactose monohydrate, corn starch, maltodextrin, sodium starch glycolate (type A), magnesium stearate, yellow film coating mixture (hypromellose 6 cP, titanium dioxide, macrogol 400, iron oxide yellow E 172).
Levomin Dosage form
Main physical and chemical properties: round tablets coated with a yellow film without coating defects.
Levomin Pharmacotherapeutic group
Hormonal contraceptives for systemic use. Progestogens and estrogens, fixed combination. Levonorgestrel and ethinyl estradiol.
ATX code G03A A07.
Levomin Pharmacological properties
The contraceptive effect of combined oral contraceptives (COCs) is based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in cervical secretion.
After oral administration, levonorgestrel is rapidly and completely absorbed. The peak serum concentration is approximately 2.3 ng / ml and is reached approximately 1.3 hours after a single dose of Levomin 30. Bioavailability is almost 100%.
Levonorgestrel binds to serum albumin and sex steroid-binding globulin. Only 1.1% of the total serum concentration is present as a free steroid, approximately 65% is specifically bound to sex steroid-binding globulin, and 35% is non-specifically bound to albumin. Ethinyl estradiol-induced increases in sex steroid-binding globulin affect the distribution of levonorgestrel between serum proteins, resulting in an increase in the sex steroid-binding globulin fraction and a decrease in the albumin-bound fraction. The apparent volume of distribution of levonorgestrel is 129 liters after a single injection.
Levonorgestrel is completely metabolized. The major metabolites in plasma are unconjugated and conjugated forms of 3α, 5β-tetrahydrolevonorgestrel. According to in vitro and in vivo studies, the major enzyme in levonorgestrel metabolism is CYP3A4. The rate of excretion from the serum is approximately 1.0 ml / min / kg.
Serum levonorgestrel levels are reduced in two phases. The distribution in the final phase is characterized by a half-life of about 25 hours.
Levonorgestrel is not excreted unchanged. Metabolites are excreted in the urine and bile (with feces) in a ratio of 1: 1. The half-life of metabolites is approximately one day.
During long-term use of Levomin 30 tablets, the level of levonorgestrel in the serum increases approximately threefold, reaching a state of equilibrium in the second half of the course of application. The pharmacokinetics of levonorgestrel are affected by the level of sex steroid-binding globulin, which increases approximately 1.5-1.6-fold after oral administration of estradiol. This also leads to a decrease in clearance and volume of distribution at steady state (0.7 ml / min / kg and about 100 l).
After oral administration, ethinyl estradiol is rapidly and completely absorbed. The peak serum concentration is almost 50 pg / ml and is reached within 1-2 hours after taking the tablet “Levomin 30”. During absorption and primary hepatic passage, ethinyl estradiol is extensively metabolised, resulting in an average oral bioavailability of approximately 45% (individual fluctuations range from 20 to 65%).
Ethinylestradiol is extensive (approximately 98%), but binds non-specifically to serum albumin and causes an increase in the serum concentration of sex steroid-binding globulin. The apparent volume of distribution was determined to be 2.8–8.6 l / kg.
Ethinylestradiol undergoes presystemic conjugation in the small intestinal mucosa and in the liver. Ethinylestradiol is mainly metabolized by aromatic hydroxylation to form many other hydroxylated and methylated metabolites, which are found as free metabolites as well as conjugated sulfates and glucuronides in serum. Metabolic clearance is approximately 2.3–7 ml / min / kg.
Serum ethinyl estradiol levels decrease biphasically with half-lives of approximately 1 hour and 10-20 hours, respectively.
Ethinylestradiol is not excreted unchanged, ethinyl estradiol metabolites are excreted in the urine and bile in a ratio of 4: 6. The half-life of metabolites is approximately one day.
The concentration of ethinyl estradiol in the serum with prolonged use of tablets “Levomin 30” increases in two phases. Due to the variable half-life of serum in the final phase at daily intake, the equilibrium concentration of ethinyl