Alondra

Treatment of endometriosis.

Treatment of endometriosis.

Inside. Before you start taking the drug Visanne should stop using hormonal contraception.

Reception scheme

The beginning of the drug Visanne possible any day of the menstrual cycle. Take one tablet a day without interruption, preferably at the same time every day, if necessary, washed down with water or other liquid. Tablets should be taken continuously, regardless of bleeding from the vagina. After the end of taking tablets from one package, start taking tablets from the next, without making a break in taking the drug.

If you skip the tablets and in the case of vomiting and/or diarrhea (if this occurs within 3-4 hours after taking the tablet), the effectiveness of the drug Visanna may decrease. If you miss one or more pills, the woman should take one tablet as soon as she remembers, and then continue taking the pills at the usual time the next day. Instead of a tablet that has not been absorbed due to vomiting or diarrhea, you should also take one tablet. There is no connection between the drug intake and food intake.

The effectiveness and safety of the drug has been proven with a duration of therapy of no more than 15 months.

Special groups of patients

Children's age. Drug Visanne not indicated for use in children before the onset of menarche.

The effectiveness of the drug Vizanna has been demonstrated in the treatment of endometriosis-associated pelvic pain in adolescents (12-18 years) with an overall favorable safety and tolerability.

When using the drug Vizanna in adolescents during the treatment period of 12 months, there was a decrease in the BMD of the lumbar region by an average of 1.2%. After discontinuation of treatment, the BMD in these patients increased again.

The decline in BMD in adolescence and in older adolescence is a cause for concern, as this period is particularly important for bone growth. It is not known whether the decrease in BMD affects the maximum bone mass in this population and increases the risk of fractures in the future.

Thus, the doctor should evaluate the ratio of the benefit of the drug to the possible risk for each adolescent patient (see "Special instructions", "Pharmacodynamics", "Pharmacokinetics").

Old age. There are no appropriate grounds for the application of the drug Visanne in patients of advanced age.

Impaired liver function. Visenna the drug is contraindicated in severe liver disease at present or in history (see "Contraindications").

Impaired renal function. There are no data indicating the need to change the dose in patients with impaired renal function.

Inside. Before taking Alondra, you must stop using hormonal contraception.

Reception scheme

You can start taking Alondra on any day of your menstrual cycle. Take one tablet a day without interruption, preferably at the same time every day, if necessary, washed down with water or other liquid. Tablets should be taken continuously, regardless of bleeding from the vagina. After the end of taking tablets from one package, start taking tablets from the next, without making a break in taking the drug.

If you skip the tablets and in the case of vomiting and / or diarrhea (if this occurs within 3-4 hours after taking the tablet), the effectiveness of Alondra may decrease. If you miss one or more pills, the woman should take one tablet as soon as she remembers, and then continue taking the pills at the usual time the next day. Instead of a tablet that has not been absorbed due to vomiting or diarrhea, you should also take one tablet. There is no connection between the drug intake and food intake.

The effectiveness and safety of the drug has been proven with a duration of therapy of no more than 15 months.

Special groups of patients

Children's age. Alondra is not indicated for use in children before the onset of menarche.

The efficacy of Alondra has been demonstrated in the treatment of endometriosis-associated pelvic pain in adolescents (12-18 years of age) with overall favorable safety and tolerability.

When using the drug Alondra in adolescents during the treatment period of 12 months, there was a decrease in the BMD of the lumbar region by an average of 1.2%. After discontinuation of treatment, the BMD in these patients increased again.

The decline in BMD in adolescence and in older adolescence is a cause for concern, as this period is particularly important for bone growth. It is not known whether the decrease in BMD affects the maximum bone mass in this population and increases the risk of fractures in the future.

Thus, the doctor should evaluate the ratio of the benefit of the drug to the possible risk for each adolescent patient (see "Special instructions", "Pharmacodynamics", "Pharmacokinetics").

Old age. There are no relevant grounds for the use of Alondra in elderly patients.

Impaired liver function. The drug Alondra is contraindicated in severe liver diseases at the present time or in the anamnesis (see "Contraindications").

Impaired renal function. There are no data indicating the need to change the dose in patients with impaired renal function.

The drug Vizanna should not be used in the presence of any of the following conditions, some of which are common to all drugs containing only the gestagenic component. If any of these States will develop on the background of drug Visanne, the use of the drug should be discontinued immediately.

acute thrombophlebitis, venous thromboembolism at present,

diseases of the heart and arteries, which are based on atherosclerotic vascular lesions (including ischemic heart disease, myocardial infarction, stroke and transient ischemic attack) at the present time or in the anamnesis,

diabetes mellitus with vascular complications,

severe liver diseases at present or in the anamnesis (in the absence of normalization of liver function tests),

liver tumors (benign and malignant) currently or in the anamnesis,

identified or suspected hormone-dependent malignancies, including breast cancer,

vaginal bleeding of unknown origin,

a history of cholestatic jaundice in pregnant women,

hypersensitivity to active substances or any of the excipients,

galactose intolerance, lactase deficiency, glucose-galactose malabsorption,

pregnancy,

breastfeeding period,

age up to 12 years (before the onset of menarche).

With caution: depression in the anamnesis, ectopic pregnancy in the anamnesis, arterial hypertension, chronic heart failure, migraine with aura, diabetes mellitus without vascular complications, hyperlipidemia, deep vein thrombophlebitis in the anamnesis, venous thromboembolism in the anamnesis (see "Special instructions").

Alondra should not be used in the presence of any of the following conditions, some of which are common to all drugs containing only the gestagenic component. If any of these conditions develop while taking Alondra, the use of the drug should be stopped immediately.

acute thrombophlebitis, venous thromboembolism at present,

diseases of the heart and arteries, which are based on atherosclerotic vascular lesions (including ischemic heart disease, myocardial infarction, stroke and transient ischemic attack) at the present time or in the anamnesis,

diabetes mellitus with vascular complications,

severe liver diseases at present or in the anamnesis (in the absence of normalization of liver function tests),

liver tumors (benign and malignant) currently or in the anamnesis,

identified or suspected hormone-dependent malignancies, including breast cancer,

vaginal bleeding of unknown origin,

a history of cholestatic jaundice in pregnant women,

hypersensitivity to active substances or any of the excipients,

galactose intolerance, lactase deficiency, glucose-galactose malabsorption,

pregnancy,

breastfeeding period,

age up to 12 years (before the onset of menarche).

With caution: depression in the anamnesis, ectopic pregnancy in the anamnesis, arterial hypertension, chronic heart failure, migraine with aura, diabetes mellitus without vascular complications, hyperlipidemia, deep vein thrombophlebitis in the anamnesis, venous thromboembolism in the anamnesis (see "Special instructions").

Side effects occur more often in the first few months of drug Visanne, and with time their numbers are decreasing. The most common side effects include: vaginal bleeding (including spotting, metrorrhagia, menorrhagia, irregular bleeding), headache, breast discomfort, decreased mood, and acne.

Table 1 shows the adverse drug reactions (NLR), distributed by organ system classes. Side effects in each frequency group are presented in descending order of frequency. Frequency is defined as frequent (from ≥1/100 to <1/10) and infrequent (from ≥1/1000 to <1/100).

Table 1

Categorized indicators of the relative frequency of NLR in women

Side effects occur more often in the first months of taking Alondra, and their number decreases over time. The most common side effects include: vaginal bleeding (including spotting, metrorrhagia, menorrhagia, irregular bleeding), headache, breast discomfort, decreased mood, and acne.

Table 1 shows the adverse drug reactions (NLR), distributed by organ system classes. Side effects in each frequency group are presented in descending order of frequency. Frequency is defined as frequent (from ≥1/100 to <1/10) and infrequent (from ≥1/1000 to <1/100).

Table 1

Categorized indicators of the relative frequency of NLR in women

Dienogest is a derivative of nortestosterone, characterized by antiandrogenic activity, which is approximately one-third of the activity of cyproterone acetate. Dienogest binds to progesterone receptors in the human uterus, having only 10% of the relative progesterone affinity. Despite its low affinity for progesterone receptors, dienogest is characterized by a powerful progestogenic effect in vivo. Dienogest has no significant androgenic, mineralocorticoid, or glucocorticoid activity in vivo.

Dienogest affects endometriosis by suppressing the trophic effects of estrogens on the autopic and ectopic endometrium due to a decrease in the production of estrogens in the ovaries and a decrease in their concentration in the plasma.

Prolonged use causes the initial decidualization of endometrial tissue followed by atrophy of endometriotic lesions. Additional properties of dienogest, such as immunological and anti-angiogenic effects, appear to contribute to its suppressive effect on cell proliferation.

The benefit of the drug Visanna compared to placebo for pelvic pain associated with endometriosis was demonstrated in 102 patients in a 3-month clinical trial. Pelvic pain associated with endometriosis was assessed on a visual analog scale (VAS, 0-100 mm). After 3 months of treatment with Visanna, a statistically significant difference was shown compared to placebo (Δ = 12.3 mm, 95% CI: 6.4–18.1, p<0.0001), as well as a clinically significant reduction in pain compared to baseline (mean = (27.4±22.9) mm).

After 3 months of treatment, 37.3% of patients showed a decrease in the intensity of pelvic pain associated with endometriosis by 50% or more without increasing the dose of the additional analgesic they took (placebo: 19.8%), 18.6% of patients showed a decrease in the intensity of pelvic pain associated with endometriosis by 75% or more without increasing the dose of the additional analgesic they took (placebo: 7.3%).

In the extended open phase of this placebo-controlled study, there was a steady decrease in pelvic pain associated with endometriosis with a duration of treatment of up to 15 months (the average reduction in pain intensity at the end of the period of use of the drug Vizanna = (43.2±21.7) mm).

In addition, the effectiveness of Vizanna in the treatment of pelvic pain associated with endometriosis was demonstrated by a 6-month comparative study of the effectiveness of Vizanna compared to leuprorelin acetate (LA), a GnRH agonist, which involved 120 patients treated with Vizanna. Pelvic pain associated with endometriosis was evaluated on a visual analog scale (VAS, 0-100 mm). In both groups, there was a clinically significant reduction in pain compared to baseline values (Visanna: (47.5±28.8) mm, LA: (46±24.8) mm). A comparable effectiveness of dienogest was demonstrated in comparison with LA (p<0.0001) based on a pre-established limit of the lowest efficiency of 15 mm

In three studies, in which a total of 252 patients received a daily dose of dienogest 2 mg, a significant reduction in endometrioid foci was demonstrated after 6 months of treatment.

A randomized, double-blind, parallel-group study (n=20-23 per dose group) examined the pharmacodynamic effects of four doses of dienogest (0.5, 1, 2, and 3 mg/day). The study duration did not exceed 72 days. Ovulation was observed in 14 and 4% of patients from the 0.5 and 1 mg dienogest groups, respectively. In patients from the groups of 2 and 3 mg of dienogest, ovulation was not observed. In 80% of patients from the group of 2 mg dienogest, ovulation was confirmed 5 weeks after the end of the drug. The contraceptive effect of the drug Visanne in larger studies have not been investigated.

A 12-month study involving 111 adolescent patients (12-18 years old, after menarche) demonstrated the effectiveness of the drug Visanna in the treatment of endometriosis symptoms (pelvic pain, dysmenorrhea and dyspareunia) in this category of patients.

BMD was evaluated in 21 adult patients before the start of treatment and after 6 months of use of the drug, there was no decrease in the average BMD index.

In a 12-month study involving 103 adolescent patients, the average relative change in the BMD index of the lumbar spine (L2 — L4 vertebrae) compared to the baseline indicator was 1.2%. 6 months after the end of treatment, within the period of continued follow-up, in a group of patients who had a decrease in BMD, this parameter was again measured, and the analysis showed an increase in the level of BMD in the direction of the initial indicator.

During the use of the drug Visanna for up to 15 months, there is a significant effect of the drug on standard laboratory parameters, including hematology, blood chemistry, liver enzymes, lipids and HbA₁, not observed.

Preclinical data obtained in the course of standard studies of pharmacological safety, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to the reproductive system do not indicate the existence of a specific risk to humans. However, it should be borne in mind that sex hormones can stimulate the growth of a number of hormone-dependent tissues and tumors.

Dienogest is a derivative of nortestosterone, characterized by antiandrogenic activity, which is approximately one-third of the activity of cyproterone acetate. Dienogest binds to progesterone receptors in the human uterus, having only 10% of the relative progesterone affinity. Despite its low affinity for progesterone receptors, dienogest is characterized by a powerful progestogenic effect in vivo. Dienogest has no significant androgenic, mineralocorticoid, or glucocorticoid activity in vivo.

Dienogest affects endometriosis by suppressing the trophic effects of estrogens on the autopic and ectopic endometrium due to a decrease in the production of estrogens in the ovaries and a decrease in their concentration in the plasma.

Prolonged use causes the initial decidualization of endometrial tissue followed by atrophy of endometriotic lesions. Additional properties of dienogest, such as immunological and anti-angiogenic effects, appear to contribute to its suppressive effect on cell proliferation.

The benefit of Alondra compared to placebo for pelvic pain associated with endometriosis was demonstrated in 102 patients in a 3-month clinical trial. Pelvic pain associated with endometriosis was assessed on a visual analog scale (VAS, 0-100 mm). After 3 months of treatment with Alondra, a statistically significant difference was shown compared to placebo (Δ = 12.3 mm, 95% CI: 6.4–18.1, p<0.0001), as well as a clinically significant reduction in pain compared to baseline (mean = (27.4±22.9) mm).

After 3 months of treatment, 37.3% of patients showed a decrease in the intensity of pelvic pain associated with endometriosis by 50% or more without increasing the dose of the additional analgesic they took (placebo: 19.8%), 18.6% of patients showed a decrease in the intensity of pelvic pain associated with endometriosis by 75% or more without increasing the dose of the additional analgesic they took (placebo: 7.3%).

In the extended open phase of this placebo-controlled trial, there was a steady decrease in pelvic pain associated with endometriosis with a duration of treatment of up to 15 months (the average reduction in pain intensity at the end of the period of use of Alondra = (43.2±21.7) mm).

In addition, the effectiveness of Alondra in the treatment of pelvic pain associated with endometriosis was demonstrated by a 6-month comparative study of the effectiveness of Alondra compared to leuprorelin acetate (LA), a GnRH agonist, which involved 120 patients treated with Alondra. Pelvic pain associated with endometriosis was evaluated on a visual analog scale (VAS, 0-100 mm). In both groups, there was a clinically significant reduction in pain compared to baseline values (Alondra: (47.5±28.8) mm, LA: (46±24.8) mm). A comparable effectiveness of dienogest was demonstrated in comparison with LA (p<0.0001) based on a pre-established limit of the lowest efficiency of 15 mm

In three studies, in which a total of 252 patients received a daily dose of dienogest 2 mg, a significant reduction in endometrioid foci was demonstrated after 6 months of treatment.

A randomized, double-blind, parallel-group study (n=20-23 per dose group) examined the pharmacodynamic effects of four doses of dienogest (0.5, 1, 2, and 3 mg/day). The study duration did not exceed 72 days. Ovulation was observed in 14 and 4% of patients from the 0.5 and 1 mg dienogest groups, respectively. In patients from the groups of 2 and 3 mg of dienogest, ovulation was not observed. In 80% of patients from the group of 2 mg dienogest, ovulation was confirmed 5 weeks after the end of the drug. The contraceptive effect of Alondra has not been studied in larger studies.

A 12-month study involving 111 adolescent patients (12-18 years old, after menarche) demonstrated the effectiveness of Alondra in the treatment of endometriosis symptoms (pelvic pain, dysmenorrhea, and dyspareunia) in this category of patients.

BMD was evaluated in 21 adult patients before the start of treatment and after 6 months of use of the drug, there was no decrease in the average BMD index.

In a 12-month study involving 103 adolescent patients, the average relative change in the BMD index of the lumbar spine (L2 — L4 vertebrae) compared to the baseline indicator was 1.2%. 6 months after the end of treatment, within the period of continued follow-up, in a group of patients who had a decrease in BMD, this parameter was again measured, and the analysis showed an increase in the level of BMD in the direction of the initial indicator.

During the use of Alondra for up to 15 months, the drug has a significant effect on standard laboratory parameters, including hematology, blood chemistry, liver enzymes, lipids, and HbA₁, not observed.

Preclinical data obtained in the course of standard studies of pharmacological safety, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to the reproductive system do not indicate the existence of a specific risk to humans. However, it should be borne in mind that sex hormones can stimulate the growth of a number of hormone-dependent tissues and tumors.

Absorption. After oral administration, dienogest is rapidly and almost completely absorbed. C_max The serum concentration of 47 ng / ml is reached approximately 1.5 hours after a single oral administration. Bioavailability is about 91%. The pharmacokinetics of dienogest in the dose range from 1 to 8 mg is characterized by dose dependence.

Distribution. Dienogest binds to serum albumin and does not bind to SHBG, nor to corticosteroid-binding globulin (CSG). 10% of the total concentration of the substance in the blood serum is in the form of a free steroid, while about 90% is non-specifically associated with albumin. The Apparent V_d (V_d/F) dienogest is 40 l.

Metabolism. Dienogest is almost completely metabolized mainly by hydroxylation with the formation of several practically inactive metabolites. Based on the research results in vitro and in vivo, the main enzyme involved in dienogest metabolism is CYP3A4. The metabolites are eliminated very quickly, so that the predominant fraction in the blood plasma is unchanged dienogest. The rate of metabolic clearance from the blood serum is 64 ml/min.

Elimination. The concentration of dienogest in the blood serum decreases biphasically. T_1/2 in the terminal phase, it is approximately 9-10 hours. After oral administration at a dose of 0.1 mg / kg, dienogest is excreted as metabolites, which are excreted through the kidneys and intestines in a ratio of approximately 3:1. T_1/2 metabolites in their excretion by the kidneys is 14 hours. After oral administration, approximately 86% of the received dose is excreted within 6 days, with the bulk being excreted in the first 24 hours, mainly by the kidneys.

C_ss. The pharmacokinetics of dienogest do not depend on the level of SHBG. The concentration of dienogest in the blood serum after daily administration increases by about 1.24 times, reaching C_ss after 4 days of reception. The pharmacokinetics of dienogest after repeated administration of the drug Visanna can be predicted based on the pharmacokinetics after a single dose.

Absorption. After oral administration, dienogest is rapidly and almost completely absorbed. C_max The serum concentration of 47 ng / ml is reached approximately 1.5 hours after a single oral administration. Bioavailability is about 91%. The pharmacokinetics of dienogest in the dose range from 1 to 8 mg is characterized by dose dependence.

Distribution. Dienogest binds to serum albumin and does not bind to SHBG, nor to corticosteroid-binding globulin (CSG). 10% of the total concentration of the substance in the blood serum is in the form of a free steroid, while about 90% is non-specifically associated with albumin. The Apparent V_d (V_d/F) dienogest is 40 l.

Metabolism. Dienogest is almost completely metabolized mainly by hydroxylation with the formation of several practically inactive metabolites. Based on the research results in vitro and in vivo, the main enzyme involved in dienogest metabolism is CYP3A4. The metabolites are eliminated very quickly, so that the predominant fraction in the blood plasma is unchanged dienogest. The rate of metabolic clearance from the blood serum is 64 ml/min.

Elimination. The concentration of dienogest in the blood serum decreases biphasically. T_1/2 in the terminal phase, it is approximately 9-10 hours. After oral administration at a dose of 0.1 mg / kg, dienogest is excreted as metabolites, which are excreted through the kidneys and intestines in a ratio of approximately 3:1. T_1/2 metabolites in their excretion by the kidneys is 14 hours. After oral administration, approximately 86% of the received dose is excreted within 6 days, with the bulk being excreted in the first 24 hours, mainly by the kidneys.

C_ss. The pharmacokinetics of dienogest do not depend on the level of SHBG. The concentration of dienogest in the blood serum after daily administration increases by about 1.24 times, reaching C_ss after 4 days of reception. The pharmacokinetics of dienogest after repeated administration of Alondra can be predicted based on the pharmacokinetics after a single dose.

Effect of other drugs on the drug Visanne

Progestogens, including dienogest, are mainly metabolized with the participation of isoenzymes of the cytochrome P450 3A4 (CYP3A4) system, located both in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 can affect the metabolism of gestagenic drugs.

Increased clearance of sex hormones due to enzyme induction may lead to reduced therapeutic effect of the drug Visanne, and cause adverse reactions, such as the changing nature of uterine bleeding.

Decreased sex hormone clearance due to enzyme inhibition may increase dienogest exposure and cause adverse reactions.

Substances that increase the clearance of sex hormones (reducing the effectiveness by inducing enzymes). Phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly oxcarbazepine, topiramate, felbamate, griseofulvin, and preparations containing St. John's wort. The induction of enzymes is usually noted a few days after the start of therapy, the maximum induction is noted for several weeks and then may persist for 4 weeks after the end of therapy.

The effect of the CYP3A4 inducer rifampicin has been studied in healthy postmenopausal women. With the simultaneous use of rifampicin with tablets containing estradiol valerate/dienogest, there was a significant decrease in C_ss and the systemic exposure of dienogest.

Systemic exposure of dienogest at C_ss, determined by the AUC value_0–24, was reduced by 83%.

Substances with a variable effect on the clearance of sex hormones. When combined with sex hormones, many drugs for the treatment of HIV and hepatitis C and NNRTI can increase or decrease the concentration of progestins in the blood plasma. In some cases, such changes may be clinically significant.

Substances that reduce the clearance of sex hormones (enzyme inhibitors). Dienogest is a substrate of cytochrome P450 3A4. Highly active inhibitors and inhibitors of CYP3A4 with moderate activity, including azole fungicides (itraconazole, voriconazole, fluconazole), verapamil, macrolides (clarithromycin, erythromycin), diltiazem and grapefruit juice can lead to an increase in the concentration of progestogen in the blood plasma.

In one study, which studied the effect of CYP3A4 inhibitors (ketoconazole, erythromycin), the concentration of estradiol valerate and dienogest in the blood plasma at C_ss were promoted. In the case of simultaneous use with a powerful inhibitor ketoconazole, the AUC value_0–24 at C_ss in dienogest, it increased by 2.86 times. When used concomitantly with a moderate CYP3A4 inhibitor erythromycin, the AUC value is_0–24 in dienogest at C_ss increased by 1.62 times. The clinical significance of these interactions has not been elucidated.

The effect of dienogest on other drugs

Based on data from inhibition studies in vitro, a clinically significant interaction of the drug Visanna with other drugs metabolized by cytochrome P450 enzymes is unlikely.

Interaction with food

Eating high-fat did not affect the bioavailability of the drug Visanne.

Other types of interaction

The use of progestogens may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, plasma concentrations of carrier proteins, such as lipid/lipoprotein fractions, carbohydrate metabolism parameters, and coagulation parameters.

The effect of other drugs on the drug Alondra

Progestogens, including dienogest, are mainly metabolized with the participation of isoenzymes of the cytochrome P450 3A4 (CYP3A4) system, located both in the intestinal mucosa and in the liver. Therefore, inducers or inhibitors of CYP3A4 can affect the metabolism of gestagenic drugs.

Increased clearance of sex hormones due to the induction of enzymes can lead to a decrease in the therapeutic effect of Alondra, as well as cause adverse reactions, such as changes in the nature of uterine bleeding.

Decreased sex hormone clearance due to enzyme inhibition may increase dienogest exposure and cause adverse reactions.

Substances that increase the clearance of sex hormones (reducing the effectiveness by inducing enzymes). Phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly oxcarbazepine, topiramate, felbamate, griseofulvin, and preparations containing St. John's wort. The induction of enzymes is usually noted a few days after the start of therapy, the maximum induction is noted for several weeks and then may persist for 4 weeks after the end of therapy.

The effect of the CYP3A4 inducer rifampicin has been studied in healthy postmenopausal women. With the simultaneous use of rifampicin with tablets containing estradiol valerate/dienogest, there was a significant decrease in C_ss and the systemic exposure of dienogest.

Systemic exposure of dienogest at C_ss, determined by the AUC value_0–24, was reduced by 83%.

Substances with a variable effect on the clearance of sex hormones. When combined with sex hormones, many drugs for the treatment of HIV and hepatitis C and NNRTI can increase or decrease the concentration of progestins in the blood plasma. In some cases, such changes may be clinically significant.

Substances that reduce the clearance of sex hormones (enzyme inhibitors). Dienogest is a substrate of cytochrome P450 3A4. Highly active inhibitors and inhibitors of CYP3A4 with moderate activity, including azole fungicides (itraconazole, voriconazole, fluconazole), verapamil, macrolides (clarithromycin, erythromycin), diltiazem and grapefruit juice can lead to an increase in the concentration of progestogen in the blood plasma.

In one study, which studied the effect of CYP3A4 inhibitors (ketoconazole, erythromycin), the concentration of estradiol valerate and dienogest in the blood plasma at C_ss were promoted. In the case of simultaneous use with a powerful inhibitor ketoconazole, the AUC value_0–24 at C_ss in dienogest, it increased by 2.86 times. When used concomitantly with a moderate CYP3A4 inhibitor erythromycin, the AUC value is_0–24 in dienogest at C_ss increased by 1.62 times. The clinical significance of these interactions has not been elucidated.

The effect of dienogest on other drugs

Based on data from inhibition studies in vitro, clinically significant interaction of Alondra with other drugs metabolized by cytochrome P450 enzymes is unlikely.

Interaction with food

High-fat food intake did not affect the bioavailability of Alondra.

Other types of interaction

The use of progestogens may affect the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, plasma concentrations of carrier proteins, such as lipid/lipoprotein fractions, carbohydrate metabolism parameters, and coagulation parameters.