Alvovizan - Instructions For Use, Reviews, Price Of Tablets, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Alvovizan

Alvovizan: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Alvovizan

ATX code: G03DB08

Active ingredient: dienogest (Dienogest)

Producer: Haupt Pharma Munster, GmbH (Germany)

Description and photo update: 2020-11-05

Prices in pharmacies: from 1454 rubles.

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Alvovizan - oral medication for the treatment of endometriosis; gestagen.

Release form and composition

The drug is produced in the form of film-coated tablets: white, biconvex, round, on one side with an engraving "2"; cross-section - a film shell and a white core (14 pcs. in a blister; in a cardboard box 2, 6 or 12 blisters and instructions for the use of Alvovizan).

1 tablet contains:

• active substance: dienogest - 2 mg;
• additional components: corn starch, lactose monohydrate, povidone K30, magnesium stearate, sodium carboxymethyl starch (sodium starch glycolate) type A;
• film shell: aquapolish white 014.17 MS [talc (E553b), hypromellose (E464), hydrogenated cottonseed oil, hyprolose (hydroxypropyl cellulose) (E463), titanium dioxide (E171)].

Pharmacological properties

Pharmacodynamics

Dienogest is a nortestosterone derivative with antiandrogenic activity, averaging ⅓ the activity of cyproterone acetate. In a woman's uterus, the drug interacts with progesterone receptors, having only 10% relative affinity for the latter, and, despite such a low affinity, shows a powerful progestogenic effect in vivo. The active substance is not characterized in vivo by significant androgenic, glucocorticoid or mineralocorticoid activity.

Dienogest has an effect on endometriosis as a result of inhibition of the trophic effects manifested by estradiol in relation to the ectopic and eutopic endometrium, due to a decrease in the production of estrogens in the ovaries and a decrease in their plasma level.

In the case of prolonged use of Alvovizan, its active component leads to the initial decidualization of the endometrial tissue with further atrophy of the endometrioid foci. The antiangiogenic and immunomodulatory properties of dienogest are thought to contribute to its inhibitory effect on cell proliferation.

In a 3-month clinical trial involving 198 patients, the drug was shown to be superior to placebo for endometriosis-associated pelvic pain, measured on a visual analogue scale (VAS) of 0–100 mm. 3 months after the start of treatment with dienogest, a statistically significant difference with placebo was found: Δ = 12.3 mm; 95% confidence interval (CI): 6.4-18.1; statistical significance (p) <0.0001. A clinically significant reduction in pain intensity compared to baseline was also shown (mean reduction = 27.4 mm ± 22.9). After 3 months of therapy, 37.3% and 18.6% of patients had a decrease in pelvic pain caused by endometriosis, respectively, by 50% and 75% or more,without increasing the dose of the additional analgesic drug used by them (in the placebo group - in 19.8 and 7.3% of patients, respectively). In the open phase of the study, there was a sustained reduction in pelvic pain with a course of administration of up to 15 months. The results of this study were confirmed by the data obtained in the active control group - the use of a gonadotropin-releasing hormone (GnRH) agonist in 252 women with endometriosis for 6 months. In three studies, 252 patients who received dienogest at a daily dose of 2 mg after 6 months of treatment showed a significant decrease in endometriotic lesions. The results of this study were confirmed by the data obtained in the active control group - the use of a gonadotropin-releasing hormone (GnRH) agonist in 252 women with endometriosis for 6 months. In three studies, 252 patients who received dienogest at a daily dose of 2 mg after 6 months of treatment showed a significant decrease in endometriotic lesions. The results of this study were confirmed by the data obtained in the active control group - the use of a gonadotropin-releasing hormone (GnRH) agonist in 252 women with endometriosis for 6 months. In three studies, 252 patients who received dienogest at a daily dose of 2 mg after 6 months of treatment showed a significant decrease in endometriotic lesions.

In a small study (in groups - n = 8), it was demonstrated that after 1 month, the drug taken at a dose of 1 mg / day caused the appearance of anovulatory status. In the course of larger studies, the contraceptive effectiveness of the drug has not been studied.

During treatment with dienogest, a moderate decrease in the content of endogenous estrogens was recorded. There is currently no long-term study of bone mineral density (BMD) and the risk of fractures during drug therapy. When assessing the BMD in 21 adult women before the start of the course and after 6 months of using Alvovizan, no decrease in the average BMD was observed. During the same period of treatment with leuprorelin acetate (LA), 29 patients showed a decrease in BMD by 4.04% ± 4.84 (Δ between groups = 4.29%; 95% CI: 1.93–6.66; p <0.0003).

In 103 of 111 adolescent girls who took part in the 1-year study, the mean relative change in BMD of the lumbar spine (L2 – L4 vertebrae) compared with the baseline value was 1.2%. After the completion of treatment 6 months later, in this group of patients with reduced BMD, when measuring this parameter, an increase in the BMD level was recorded towards the initial indicator to a level of 0.6%.

Hematology, blood chemistry, indicators of glycated hemoglobin (HbA1C), lipids, liver enzymes, as well as other standard laboratory parameters during therapy with Alvovizan for up to 15 months were not significantly affected.

According to preclinical data obtained in the course of studies of the toxicity of dienogest with repeated administration, its genotoxicity, carcinogenicity, toxicity for the reproductive system, the specific risk of using Alvovizan in humans has not been established. However, it is required to remember about the ability of sex hormones to stimulate the growth of some hormone-dependent tumors.

Pharmacokinetics

Dienogest, when taken orally, is almost completely absorbed intensively. The maximum concentration (C _max) in plasma after a single oral administration is noted after 1.5 hours and is 47 ng / ml. The bioavailability of the active substance is approximately 91%, the pharmacokinetics in the dose range of 1-8 mg is dose-dependent.

The apparent volume of distribution (V _d / F) of the drug is 40 liters. In plasma, the agent binds to albumin and does not interact with sex hormone binding globulin (SHBG), as well as corticoid-binding globulin (CBG). About 10% of the total plasma content of a substance in the blood is in the form of a free steroid, and about 90% is nonspecifically bound to albumin.

Dienogest is almost completely biotransformed, mainly through hydroxylation with the formation of several metabolites that have practically no activity. The main enzymes responsible for its metabolism, according to the results of in vitro and in vivo studies, include CYP3A4. Since metabolites are excreted very rapidly, unchanged dienogest is the dominant fraction in plasma. The metabolic clearance rate (Cl / F) from the blood is 64 ml / min.

The serum concentration of dienogest in the blood decreases in two phases, in the terminal phase the half-life (T _1/2) is on average 9-10 hours. After oral administration of Alvovizan at a dose of 0.1 mg / kg, it is excreted as metabolites through the intestine and by the kidneys in a ratio of approximately 1 ÷ 3, with elimination by the kidneys, T _{1/2 of} metabolites is 14 hours. Approximately 86% of the dose received orally is excreted within 6 days, with the main part in the first 24 hours, mainly by the kidneys.

The SHBG level does not affect the pharmacokinetics of dienogest. The content of the latter in the blood plasma after daily administration increases approximately 1.24 times, and after 4 days of administration reaches an equilibrium concentration. After repeated use of Alvovizan, its pharmacokinetics can be predicted on the basis of that after a single dose.

Indications for use

Alvovizan is recommended for use in the treatment of endometriosis.

Contraindications

Absolute (in case of development against the background of treatment of any of the following conditions / diseases, Alvovizan should be stopped immediately):

• diseases of the heart and arteries associated with atherosclerotic vascular lesions, including myocardial infarction, ischemic heart disease (IHD), cerebrovascular accident (including in history);
• venous thromboembolism (VTE), acute venous thrombophlebitis;
• benign or malignant liver tumors (including a history);
• severe liver damage at the present time or in history, before reaching normal liver function indicators;
• diabetes mellitus with angiopathy;
• bleeding from the vagina of unknown etiology;
• diagnosed / suspected hormone-dependent malignant lesions of the genital organs or breast;
• lactase deficiency, hereditary lactose intolerance, glucose-galactose malabsorption syndrome (1 tablet contains lactose monohydrate at a dose of 57.2 mg);
• age up to 18 years;
• pregnancy and breastfeeding;
• hypersensitivity to any of the components of Alvovizan.

Relative (taking the drug is required with extreme caution):

• diabetes mellitus in the absence of vascular complications (to an insignificant extent affects glucose tolerance and peripheral insulin resistance);
• chronic heart failure (CHF);
• arterial hypertension;
• a history of an ectopic pregnancy;
• migraine with aura;
• history of deep vein thrombophlebitis;
• a personal / family history of VTE;
• hyperlipidemia;
• a history of depression.

Alvovizan, instructions for use: method and dosage

Alvovizan tablets are taken orally.

Before starting drug therapy, it is required to stop using any hormonal contraception. If it is necessary to carry out contraception while taking it, it is possible to use non-hormonal methods (for example, barrier).

The drug can be started on any day of the menstrual cycle. It is recommended to take tablets 1 pc. per day in a continuous mode, regardless of the onset of vaginal bleeding, preferably at the same time of day, drinking a small amount of liquid if necessary. Alvovizan can be taken both with meals and on an empty stomach.

In the case when all the tablets from one package have been taken, you should start taking the tablets from the next package without interruption.

If the next dose of the pill was missed or vomiting and / or diarrhea occurred within 3-4 hours after administration, the effect of the drug may decrease. As a result, if you miss one or more tablets, you need to drink only 1 tablet as soon as possible, and then the next day to continue the course of therapy at the usual time. When absorption of the drug has been impaired due to vomiting or diarrhea, 1 additional tablet should be taken.

The course of therapy with Alvovizan is 6 months. The decision on the subsequent use of the drug is made by the attending physician, taking into account the clinical picture.

Side effects

When taking Alvovizan, the following negative side reactions from systems and organs may develop:

• metabolism and nutrition: often - an increase in body weight; infrequently - increased appetite, weight loss;
• nervous system: often - headache, migraine; infrequently - impaired concentration, imbalance of the autonomic nervous system;
• blood and lymphatic system: infrequently - anemia;
• organ of vision: infrequently - a feeling of dry eyes;
• organ of hearing and labyrinthine disorders: infrequently - ringing in the ears;
• mental disorders: often - nervousness, depressed mood, mood lability, sleep disturbance, loss of libido; infrequently - anxiety, mood swings, depression;
• respiratory system, organs of the chest and mediastinum: infrequently - shortness of breath;
• cardiovascular system: infrequently - palpitations, unspecified circulatory disorders, arterial hypotension;
• skin and subcutaneous tissues: often - acne, alopecia; infrequently - itching, dry skin, hyperhidrosis, dandruff, abnormal hair growth, onychorexis, hirsutism, dermatitis, pigmentation disorders, photosensitivity reactions;
• gastrointestinal tract (GIT): often - a feeling of bloating, flatulence, vomiting, nausea, abdominal pain; infrequently - abdominal discomfort, diarrhea / constipation, gingivitis, inflammatory lesions of the digestive tract;
• kidney and urinary tract: infrequently - urinary tract infections;
• musculoskeletal and connective tissue: often - back pain; infrequently - muscle spasms, heaviness in the limbs, pain in the limb, pain in the bones;
• genitals and mammary gland: often - hot flashes, discomfort in the mammary glands, bleeding from the genital tract, including spotting spotting, ovarian cyst; infrequently - dryness of the vulva and vagina, vaginal candidiasis, pain in the pelvic region, discharge from the genitals, thickening of the breast tissue, atrophic vulvovaginitis, fibrocystic breast disease;
• others: often - irritability, asthenic state; infrequently - edema.

During drug treatment, undesirable effects were most often observed in the first months of admission and decreased with continued therapy. The most common adverse reactions observed when using Alvovizan are: discomfort in the mammary glands, depressed mood, headache, acne. There may be changes in the nature of bleeding in the form of amenorrhea, smearing discharge, irregular bleeding.

Overdose

There are no reports of serious violations in case of drug overdose. The daily use of dienogest at a dose of 20–30 mg for 24 weeks was well tolerated. In the course of studies of the acute toxicity of the drug, the threat of acute adverse events as a result of accidental intake of dienogest in a dose many times higher than the daily dose was not identified.

There is no specific antidote, treatment for a possible overdose of Alvovizan is symptomatic.

special instructions

Progestogen therapy can be started only after excluding the development of pregnancy. In the vast majority of patients during treatment with Alvovizan, ovulation is suppressed, however, dienogest at a dose of 2 mg does not apply to contraceptives. Within two months after the completion of the course of treatment for endometriosis, the restoration of the physiological menstrual cycle is recorded.

In women taking contraceptive drugs that include only a gestagen component, the risk of ectopic pregnancy is higher when compared with women using combined oral contraceptives (COCs). As a result, before using Alvovizan with an existing dysfunction of the fallopian tubes or an indication in the history of an ectopic pregnancy, it is necessary to carefully assess the balance of benefits and risks.

While taking dienogest, there may be an increase in uterine bleeding, for example, in patients with leiomyomas or uterine adenomyosis. If a serious and prolonged uterine bleeding is discovered, the threat of anemia (sometimes severe) is aggravated. When this complication appears, it is necessary to resolve the issue of canceling Alvovizan.

During epidemiological studies, there was an insufficiently convincing relationship between the use of progestogen monopreparations and an increased risk of myocardial infarction or cerebral thromboembolism. The threat of developing cardiovascular and cerebral pathologies is more likely associated with increasing age, smoking or the presence of arterial hypertension. Against the background of the use of funds that include only gestagen, with arterial hypertension, the likelihood of a stroke may slightly increase.

With progestogen monopreparation therapy, the risk of VTE is slightly increased. Known risk factors for VTE are a family history of the disease (in a brother, sister, or parent under 50), obesity, age, prolonged immobilization, major trauma, or major surgery. In the case of long-term immobilization, it is required to interrupt the use of dienogest (at least 4 weeks before the planned operation) and resume its intake no earlier than 2 weeks after the absolute restoration of motor activity.

When using Alvovizan in the postpartum period, the aggravation of the risk of thromboembolism should be taken into account. If the first symptoms occur or if you suspect the development of arterial / venous thrombosis, you must urgently stop taking the pills.

In women using hormonal contraceptives containing only a gestagenic component, the risk of breast cancer is approximately the same as when using COCs. Data on progestogen monopreparations, however, have been established in significantly smaller patient groups and are therefore less conclusive than data on COCs. A causal relationship based on these studies cannot be reliably confirmed.

During the period of use of progestogens, in rare cases, benign, and extremely rarely, malignant neoplasms of the liver were recorded. Sometimes these tumors caused life-threatening intra-abdominal bleeding. If, during treatment, severe pain in the upper abdomen occurs, there are signs of intra-abdominal bleeding, or the liver is enlarged, the differential diagnosis should take into account the likelihood of a liver tumor.

Since when using Alvovizan, a decrease in BMD and a moderate decrease in the content of endogenous estrogens are recorded, the possibility of osteoporosis should be taken into account, especially in the presence of an increased risk of this disease. It is important for patients of all ages to receive vitamin D and calcium supplements while following any diet or vitamin supplementation.

If depression in a serious form, chronic, clinically significant arterial hypertension, cholestatic jaundice and / or cholestatic pruritus (which first appeared during the previous use of sex steroids or during pregnancy) develops during the period of therapy, Alvovizan should be canceled and appropriate treatment initiated.

When using dienogest, it is required to carefully monitor the condition of patients with diabetes mellitus, especially if there is a history of diabetes mellitus in pregnant women.

In some cases, mainly with a history of chloasma of pregnant women, chloasma may develop during treatment with Alvovizan. If you have a predisposition to the appearance of this lesion, you must beware of exposure to ultraviolet radiation or direct sunlight.

Taking Alvovizan can provoke the appearance of persistent ovarian follicles, called functional ovarian cysts. As a rule, the development of such follicles is not accompanied by clinical manifestations, but sometimes pain in the pelvic region may occur.

Influence on the ability to drive vehicles and complex mechanisms

Alvovizan does not have a negative effect on the ability to drive vehicles and other complex mechanisms, but if there are disturbances in concentration while taking, care must be taken.

Application during pregnancy and lactation

Data on dienogest therapy during pregnancy are limited.

When conducting preclinical studies, carcinogenicity, reproductive toxicity and genotoxicity of the drug were not detected. Alvovizan is not prescribed during pregnancy, since during this period there is no need for endometriosis therapy.

Animal studies have shown that dienogest is excreted in breast milk. Alvovizan is contraindicated for use during lactation, since it is not known whether dienogest penetrates into human breast milk. If it is necessary to take it during this period, it is necessary to resolve the issue of stopping breastfeeding.

Pediatric use

Therapy with the drug in adolescent girls under 18 years of age is contraindicated, due to the lack of data confirming the efficacy and safety of using dienogest in patients of this age group.

With impaired renal function

In the presence of impaired renal function, there is no need to adjust the dose of Alvovizan.

For violations of liver function

Patients with severe liver disease, current or in history (in the absence of normalization of liver test results), as well as benign or malignant liver tumors (including data in history), treatment with Alvovizan tablets is contraindicated.

Use in the elderly

Elderly people do not have reasonable indications for the use of Alvovizan.

Drug interactions

Dienogest, like other progestogens, is metabolized in the liver and intestinal mucosa, mainly with the participation of the isoenzyme of the cytochrome P450 system - CYP3A4. As a result, inducers / inhibitors of this isoenzyme can affect the metabolism of the drug.

The effect of other concurrently taken drugs / drugs on dienogest:

• inducers of microsomal cytochrome P450 enzymes, including barbiturates, phenytoin, rifampicin, carbamazepine, primidone, topiramate, griseofulvin, oxcarbazepine, felbamate and agents containing St. John's wort (Hypericum perforatum): increase hormone clearance in connection with the induction can reduce the therapeutic effect of dienogest and contribute to the enhancement of existing or the development of new side reactions (including a change in the nature of uterine bleeding); the induction of enzymes is recorded already a few days after the start of the course of treatment, the maximum induction is usually achieved within a few weeks; after completion of therapy, an increase in enzyme activity can be observed for 4 weeks;rifampicin in combination with dienogest and estradiol led to a pronounced decrease in equilibrium concentrations and systemic exposure of the latter, in the equilibrium state systemic exposures of dienogest and estradiol, determined by the value of the area under the pharmacokinetic curve "concentration - time" (AUC_{0–24 h}), respectively, decreased by 83 and 44%;
• inhibitors of the CYP3A4 isoenzyme, including ketoconazole, erythromycin, cimetidine, verapamil, macrolides, diltiazem, antidepressants: reduce the clearance of sex hormones as a result of inhibition of enzymes, which can lead to an increase in the plasma concentration of dienogest in the blood and the development of undesirable events; ketoconazole, a strong inhibitor of CYP3A4, causes an increase in the equilibrium concentration of the AUC value of _{0-24 h of} dienogest by 2.9 times, erythromycin (a moderate inhibitor) by 1.6 times;
• substances that have a variable effect on the clearance of sex hormones - protease inhibitors and non-nucleoside reverse transcriptase inhibitors for the treatment of viral hepatitis C and HIV infection: they can contribute to both an increase and a decrease in the progestogen content in the blood, sometimes the total effects of these changes can have clinical significance.

According to in vitro studies, a clinically significant interaction of Alvovizan with cytochrome P450 enzymes, leading to a significant effect on the metabolic transformation of other drugs, is unlikely.

The intake of dienogest with food rich in fats did not affect the bioavailability of the drug.

The use of progestogens can affect the results of a number of laboratory studies, including the biochemical parameters of the liver, kidneys, adrenal glands, thyroid gland, plasma concentrations of proteins (carriers) - CSG, lipoprotein fractions, lipids; coagulation parameters and parameters of carbohydrate metabolism. Typically, these changes remain within the normal laboratory values.

Analogs

Zafrilla and Vizanna are analogues of Alvovizan.

Terms and conditions of storage

Keep out of the reach of children at a temperature not exceeding 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Alvovizan

The few reviews about Alvovizan, left by patients on specialized sites, are almost all positive. The drug is considered an effective treatment for endometriosis, providing a significant and sustained reduction in pelvic pain during the course of administration. The advantages of the drug also include good tolerance, convenient dosing regimen and the possibility of long-term treatment.

Sometimes there are complaints about the lack of the drug in the pharmacy network.

The price of Alvovizan in pharmacies

The price of Alvovizan in the form of tablets (2 mg), film-coated, can be 1640-1800 rubles. for 28 pcs. packaged.

Alvovizan: prices in online pharmacies

Drug name Price Pharmacy

Alvovizan 2 mg film-coated tablets 28 pcs. 1454 RUB Buy

Alvovizan pills p.p. 2mg 28pcs 1663 RUB Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!