×
Components:
Dienogest, Estradiol
Method of action:
Antiplasmic, Contraceptive, Sex Hormones And Modulators Of The Genital System
Available in countries
See all
close
Medically reviewed by Fedorchenko Olga Valeryevna, Pharmacy-Provisor. Last updated on 2019.12.09

Name of the medicinal product

Lafleur

Qualitative and quantitative composition

Dienogest; Estradiol

Therapeutic indications

The information provided in Therapeutic indications of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Therapeutic indications in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close

Oral Contraception

Lafleur® is indicated for use by women to prevent pregnancy.

The efficacy of Lafleur in women with a body mass index (BMI) of > 30 kg/m² has not been evaluated.

Heavy Menstrual Bleeding

Lafleur is also indicated for the treatment of heavy menstrual bleeding in women without organic pathology who choose to use an oral contraceptive as their method of contraception.

Dosage (Posology) and method of administration

The information provided in Dosage (Posology) and method of administration of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Dosage (Posology) and method of administration in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close

How To Take Lafleur

To achieve maximum contraceptive effectiveness, Lafleur must be taken exactly as directed. Take one tablet by mouth at the same time every day. Tablets must be taken in the order directed on the blister pack. Tablets should not be skipped or intake delayed by more than 12 hours. For patient instructions for missed pills, see FDA-Approved Patient Labeling.

How To Start Lafleur

Instruct the patient to begin taking Lafleur on Day 1 of her menstrual cycle (that is, the first day of her menstrual bleeding). See FDA-Approved Patient Labeling. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 9 days.

For postpartum women who do not breastfeed or after a second trimester abortion, start Lafleur no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Lafleur postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Lafleur for 9 consecutive days. The possibility of ovulation and conception prior to initiation of medication should also be considered.

If the patient is switching from a combination hormonal method such as:

    • Another pill
    • Vaginal ring
    • Patch
  • Instruct her to take the first dark yellow pill on the first day of her withdrawal bleed. She should not continue taking the pills from her previous birth control pack. If she does not have a withdrawal bleed, rule out pregnancy before starting Lafleur.
  • If she previously used a vaginal ring or transdermal patch, she should start using Lafleur on the day the ring or patch is removed.
  • Instruct the patient to use a non-hormonal back-up method such as a condom or spermicide for the first 9 days.

If the patient is switching from a progestin-only method such as a:

    • Progestin-only pill
    • Implant
    • Intrauterine system
    • Injection
  • Instruct her to take the first dark yellow pill on the day she would have taken her next progestin-only pill or on the day of removal of her implant or intrauterine system or on the day when she would have had her next injection.
  • Instruct the patient to use a non-hormonal back-up method such as a condom or spermicide for the first 9 days.

Advice In Case Of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3-4 hours after taking a colored tablet, this can be regarded as a missed tablet.

Contraindications

The information provided in Contraindications of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Contraindications in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close

Do not prescribe Lafleur to women who are known to have the following:

  • A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
    • Smoke, if over age 35
    • Have deep vein thrombosis or pulmonary embolism, now or in the past
    • Have cerebrovascular disease
    • Have coronary artery disease
    • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)
    • Have inherited or acquired hypercoagulopathies
    • Have uncontrolled hypertension
    • Have diabetes mellitus with vascular disease
    • Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35
  • Undiagnosed abnormal uterine bleeding
  • Breast cancer or other estrogen-or progestin-sensitive cancer, now or in the past
  • Liver tumors, benign or malignant, or liver disease.
  • Pregnancy, because there is no reason to use COCs during pregnancy.

Special warnings and precautions for use

The information provided in Special warnings and precautions for use of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Special warnings and precautions for use in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Thromboembolic Disorders And Other Vascular Problems

Stop Lafleur if an arterial or venous thrombotic event (VTE) occurs.

The use of COCs increases the risk of venous thromboembolism. However, pregnancy increases the risk of venous thromboembolism as much or more than the use of COCs. The risk of VTE in women using COCs has been estimated to be 3 to 9 per 10,000 woman-years. The risk of VTE is highest during the first year of use. Data from a large, prospective cohort safety study of various COCs suggest that this increased risk, as compared to that in non-COC users, is greatest during the first 6 months of COC use. Data from this safety study indicate that the greatest risk of VTE is present after initially starting a COC or restarting (following a 4 week or greater pill-free interval) the same or a different COC.

Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events.

The risk of thromboembolic disease due to oral contraceptives gradually disappears after COC use is discontinued.

If feasible, stop Lafleur at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism.

Start Lafleur no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older ( > 35 years of age), hypertensive women who also smoke. COCs also increase the risk for stroke in women with other underlying risk factors.

Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.

Stop Lafleur if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.

Carcinoma Of The Breasts And Reproductive Organs

Women who currently have or have had breast cancer should not use Lafleur because breast cancer is a hormonallysensitive tumor.

There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings.

Some studies suggest that COCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which these findings may be due to differences in sexual behavior and other factors.

Endometrial biopsies performed in a subset of subjects in a Phase 3 Lafleur clinical trial did not reveal any unexpected or concerning findings for subjects taking COCs.

Liver Disease

Discontinue Lafleur if jaundice develops. Steroid hormones may be poorly metabolized in patients with impaired liver function. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded.

Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage.

Studies have shown an increased risk of developing hepatocellular carcinoma in long-term ( > 8 years) COC users. However, the attributable risk of liver cancers in COC users is less than one case per million users.

Oral contraceptive-related cholestasis may occur in women with a history of pregnancy-related cholestasis. Women with a history of COC-related cholestasis may have the condition recur with subsequent COC use.

High Blood Pressure

For women with well-controlled hypertension, monitor blood pressure and stop Lafleur if blood pressure rises significantly. Women with uncontrolled hypertension or hypertension with vascular disease should not use COCs.

An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women and with extended duration of use. The incidence of hypertension increases with increasing concentration of progestin.

Gallbladder Disease

Studies suggest a small increased relative risk of developing gallbladder disease among COC users.

Carbohydrate And Lipid Metabolic Effects

Carefully monitor prediabetic and diabetic women who are taking Lafleur. COCs may decrease glucose tolerance in a dose-related fashion.

Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs.

Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.

Headache

If a woman taking Lafleur develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Lafleur if indicated.

An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.

Bleeding Irregularities

Breakthrough bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different COC.

Women who are not pregnant and use Lafleur, may experience amenorrhea. Based on patient diaries, amenorrhea occurs in approximately 16% of cycles in women using Lafleur. Pregnancy should be ruled out in the event of amenorrhea occurring in two or more consecutive cycles. Some women may encounter amenorrhea or oligomenorrhea after stopping COCs, especially when such a condition was pre-existent.

Based on patient diaries from three clinical trials evaluating the safety and efficacy of Lafleur for contraception, 10-23% of women experienced intracyclic bleeding per cycle.

COC Use Before Or During Early Pregnancy

Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb-reduction defects are concerned, when taken inadvertently during early pregnancy. Oral contraceptive use should be discontinued if pregnancy is confirmed.

The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy.

Depression

Women with a history of depression should be carefully observed and Lafleur discontinued if depression recurs to a serious degree.

Interference With Laboratory Tests

The use of COCs may change the results of some laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increase with use of COCs.

Monitoring

A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare.

Drug Interactions

Women who take medications that are strong cytochrome P450 3A4 (CYP3A4) inducers (for example, carbamazepine, phenytoin, rifampicin, and St. John's wort) should not choose Lafleur as their oral contraceptive while using these inducers and for at least 28 days after discontinuation of these inducers due to the possibility of decreased contraceptive efficacy.

Other Conditions

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema. Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking COCs.

Patient Counseling Information

See “FDA-approved patient labeling (PATIENT INFORMATION). ”

  • Counsel patients that cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs.
  • Counsel patients that the increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4 week or greater pill-free interval) the same or a different COC.
  • Counsel patients that Lafleur does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
  • Counsel patients on WARNINGS AND PRECAUTIONS associated with COCs.
  • Inform patients that Lafleur is not indicated during pregnancy. If pregnancy occurs during treatment with Lafleur, instruct the patient to stop further intake.
  • Counsel patients to take one tablet daily by mouth at the same time every day in the exact order noted on the blister. Instruct patients what to do in the event pills are missed. See What Should I Do if I Miss any Pills section in FDA-Approved Patient Labeling.
  • Counsel women who are taking strong CYP3A4 inducers (for example, carbamazepine, phenytoin, rifampicin, and St. John's wort) not to choose Lafleur as their oral contraceptive due to the possibility of decreased contraceptive efficacy.
  • Counsel patients to use a back-up or alternative method of contraception when weak or moderate enzyme inducers are used with Lafleur.
  • Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established.
  • Counsel any patient who starts COCs postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken Lafleur for 9 consecutive days.
  • Counsel patients that amenorrhea may occur. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a 24 month carcinogenicity study in mice dosed orally with dienogest by gavage with doses of 5, 15 and 50 mg/kg/day (males) and 10, 30 and 100 mg/kg/day (females), the systemic exposures in the females were 1.1, 3.5, and 10.6 times the exposure (AUC of dienogest) of women taking a 3 mg dose. A statistically significantly higher incidence of stromal polyps of the uterus was observed in females given 100 mg/kg. In a similar study in rats given 1, 3, and 10 mg/kg for 104 weeks, 0.2, 1.4, and 6.1 times the exposure of women taking a 3 mg dose, there were no statistically significant drug-related neoplasms.

Dienogest was not mutagenic in in vitro reverse mutation tests in bacteria, in chromosome aberration tests in human peripheral lymphocytes, mouse lymphoma cells, and Chinese hamster lung cells, and tests of unscheduled DNA synthesis (UDS) in rat and human liver cells. Dienogest was also negative in an in vivo mouse micronucleus test, a rat liver initiation-promotion model, and an in vitro/in vivo UDS test in female rats.

Use In Specific Populations

Pregnancy

There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.

The administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy. COCs should not be used during pregnancy to treat threatened or habitual abortion.

Women who do not breastfeed may start COCs no earlier than four weeks postpartum.

Nursing Mothers

When possible, advise the nursing mother to use other forms of contraception until she has weaned her child. Estrogen-containing COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.

Pediatric Use

Safety and efficacy of Lafleur have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.

Geriatric Use

Lafleur has not been studied in postmenopausal women and is not indicated in this population.

Patients With Renal Impairment

The pharmacokinetics of Lafleur has not been studied in subjects with renal impairment, but an effect requiring dose adjustment is unlikely to be present.

Patients With Hepatic Impairment

The pharmacokinetics of Lafleur has not been studied in subjects with hepatic impairment. Steroid hormones may be poorly metabolized in patients with impaired liver function. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal.

Body Mass Index

The safety and efficacy of Lafleur in women with a BMI of > 30 kg/m² has not been evaluated.

Undesirable effects

The information provided in Undesirable effects of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Undesirable effects in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:

  • Serious cardiovascular events and stroke
  • Vascular events
  • Liver disease

Adverse reactions commonly reported by COC users are:

  • Irregular uterine bleeding
  • Nausea
  • Breast tenderness
  • Headache

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Contraception and Heavy Menstrual Bleeding Studies

A total of 2,131 women, 18 to 54 years of age, who took at least one dose of Lafleur were enrolled in four clinical phase 3 trials. A total of 1,867 subjects were included in two clinical phase 3 studies with a treatment duration up to 28 cycles with Lafleur as an oral contraceptive and 264 subjects in the two phase 3 clinical trials with a treatment duration of 7 cycles evaluating Lafleur in the treatment of heavy, prolonged, and/or frequent menstrual bleeding in women without organic pathology.

Adverse Reactions Leading to Study Discontinuation: 11.4% of the women discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were menstrual disorder (metrorrhagia, menorrhagia, menstruation irregular, genital hemorrhage, vaginal hemorrhage, dysfunctional uterine bleeding) (2.3%); mood changes (depression, mood swings, mood altered, depressed mood, dysthymic disorder, crying) (1.2%); acne (1.1%), headache (including migraines) (1.1%), and weight increased (0.7 %).

Common Adverse Reactions ( ≥ 2%): headache (including migraines) (12.7%), breast pain, discomfort or tenderness (7.0%), menstrual disorders (metrorrhagia, menstruation irregular, menorrhagia, vaginal hemorrhage, dysfunctional uterine bleeding, genital hemorrhage, abnormal withdrawal bleeding, uterine hemorrhage) (6.9%), nausea or vomiting (6.0%), acne (3.9%), mood changes (depression, mood swings, depressed mood, mood altered, affect lability, dysthymic disorder, crying) (3.0%) and increased weight (2.9%).

Serious Adverse Reactions: myocardial infarction (2 cases), ruptured ovarian cyst (2 cases), deep vein thrombosis, focal nodular hyperplasia of the liver, uterine leiomyoma, acute cholecystitis, and chronic acalculous cholecystitis.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Lafleur. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Vascular disorders: Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, cerebral thrombosis, myocardial infarction and stroke), hypertension

Hepatobiliary disorders: Gallbladder disease, hepatitis

Immune system disorders: Hypersensitivity

Metabolism and nutrition disorders: Fluid retention, hypertriglyceridemia

Nervous system disorders: Dizziness

Skin and subcutaneous tissue disorders: Chloasma, angioedema, erythema nodosum, erythema multiforme

Gastrointestinal disorders: Gastrointestinal symptoms (for example, abdominal pain)

Infections and infestations: Vulvovaginal candidiasis

Overdose

The information provided in Overdose of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Overdose in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close

There have been no reports of serious ill effects from overdose, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.

Pharmacodynamic properties

The information provided in Pharmacodynamic properties of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Pharmacodynamic properties in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close

The estrogen in Lafleur is estradiol valerate, a synthetic prodrug of 17ß-estradiol. The progestin in Lafleur is dienogest (DNG). DNG displays properties of 19-nortestosterone derivatives as well as properties associated with progesterone derivatives.

Cardiac Electrophysiology

The effect of Lafleur on QT prolongation was evaluated in a randomized, double-blind, positive (moxifloxacin 400 mg) and negative (placebo) controlled crossover study in healthy subjects. A total of 53 subjects were administered Lafleur (containing 3 mg dienogest and 2 mg estradiol valerate), dienogest 10 mg, and placebo as once daily doses for 4 days, and moxifloxacin 400 mg as a single oral dose. The upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on Fridericia's correction method (QTcF) was below 10 msec, the threshold for regulatory concern.

Pharmacokinetic properties

The information provided in Pharmacokinetic properties of Lafleur is based on data of another medicine with exactly the same composition as the Lafleur of the medicine (Dienogest, Estradiol). Be careful and be sure to specify the information on the section Pharmacokinetic properties in the instructions to the drug Lafleur directly from the package or from the pharmacist at the pharmacy.
more... close
Absorption

After oral administration of estradiol valerate, cleavage to 17β-estradiol and valeric acid takes place during absorption by the intestinal mucosa or in the course of the first liver passage. This gives rise to estradiol and its metabolites, estrone and other metabolites. Maximum serum estradiol concentrations of 73.3 pg/mL are reached at a median of approximately 6 hours (range: 1.5–12 hours) and the area under the estradiol concentration curve [AUC(0–24h)] was 1301 pg·h/mL after single ingestion of a tablet containing 3 mg estradiol valerate under fasted condition on Day 1 of the 28-day sequential regimen.

Bioavailability of dienogest is about 91%. Maximum serum dienogest concentrations of 91.7 ng/mL are reached at a median of approximately 1 hour (range: 0.5–1.5 hour) and the area under the dienogest concentration curve [AUC(0– 24h)] was 964 ng/mL after single oral administration of Lafleur tablet containing 2 mg estradiol valerate/3 mg dienogest under fasted condition. The pharmacokinetics of dienogest are dose-proportional within the dose range of 1–8 mg. Steady state is reached after 4 days of the same dosage of 2 mg dienogest. The mean accumulation ratio for AUC (0–24h) is approximately 1.24.

The mean plasma pharmacokinetic parameters at steady state following repeated oral doses of a 2 mg estradiol valerate/3 mg dienogest combination tablet in fertile women under fasted condition are reported in Table 1.

Table 1: Arithmetic Mean (SD) Serum Pharmacokinetic Parameters at Steady-state (on Day 24) following Repeated Oral Doses of 2 mg EV/3 mg DNG on Days 8–24 of the 28 day Regimen in Fertile Women under Fasted Condition (N=15)

Parameter Dienogest Estradiol Estrone
C 85.2 (19.7) ng/ml 70.5 (25.9) pg/ml 483 (198) pg/ml
Tmax (h)a 1.5 (1-2) 3 (1.5-12) 4 (3-12)
AUC(0-24h) 828 (187) ngh/ml 1323 (480) pg•h/ml 7562 (3403) pg•h/ml
t½ (h) 12.3 (1.4) NA NA
a Median (range) for Tmax
Cmax = Maximum serum concentration
Tmax = Time to reach maximum concentration
AUC(0–24h) = Area under the concentration-time curve from 0 h data point up to 48 h post-administration
NA: Data not available

Food Effect

Concomitant food intake in women resulted in a 28% decrease for dienogest Cmax and 23% increase of estradiol Cmax while the exposure (AUC) of both dienogest and estradiol did not change.

Distribution

In serum, 38% of estradiol is bound to sex hormone-binding globulin (SHBG), 60% to albumin and 2–3% circulates in free form. An apparent volume of distribution of approximately 1.2 L/kg was determined after intravenous (IV) administration.

A relatively high fraction (10%) of circulating dienogest is present in the free form, with approximately 90% being bound non-specifically to albumin. Dienogest does not bind to SHBG and corticosteroid-binding globulin (CBG). The volume of distribution at steady state (Vd,ss) of dienogest is 46 L after the IV administration of 85 mcg 3H-dienogest.

Metabolism

After oral administration of estradiol valerate, approximately 3% of the dose is directly bioavailable as estradiol. Estradiol undergoes an extensive first-pass effect and a considerable part of the dose administered is already metabolized in the gastrointestinal mucosa. The CYP 3A family is known to play the most important role in human estradiol metabolism. Together with the pre-systemic metabolism in the liver, about 95% of the orally administered dose becomes metabolized before entering the systemic circulation. The main metabolites are estrone and its sulfate or glucuronide conjugates.

Dienogest is extensively metabolized by the known pathways of steroid metabolism (hydroxylation, conjugation), with the formation of endocrinologically mostly inactive metabolites. CYP3A4 was identified as a predominant enzyme catalyzing the metabolism of dienogest.

Excretion

Estradiol and its metabolites are mainly excreted in urine, with about 10% being excreted in the feces. The terminal half-life of estradiol is approximately 14 hours.

Dienogest is mainly excreted renally in the form of metabolites and unchanged dienogest is the dominating fraction in plasma. The terminal half-life of dienogest is approximately 11 hours.

Site feedback

How easy to use our site?

Commentary is required, without it we won't know how to become better
The maximum length of review is 1000 symbols

Thanks!

You help us to become better