Androkur - instructions for use, doses, side effects, contraindications

lactose monohydrate - 63.40 mg, corn starch - 44.00 mg, povidone 25000 - 1.35 mg, silicon colloidal dioxide, micronized -1.00 mg, magnesium stearate - 0.25 mg.

Description:

Round from white to light yellow color tablets with a risk on one side, on the other side is engraved a hexagon, inside which the letters "BW".

Pharmacotherapeutic group:Antiandrogen

ATX: & nbsp

G.03.H.A.01 Cyproterone

Pharmacodynamics:

Androkur® is a hormonal antiandrogenic drug.

The active ingredient of Androcour® weakens the effect of male sex hormones (androgens), which are produced in small amounts also in the female body. Competitive displacement of androgens in target organs leads to relief of symptoms in androgen-dependent conditions, such as pathological hair growth in hirsutism, androgenic alopecia and increased function of sebaceous glands in acne and seborrhea.The decrease in androgen concentration, caused by the antigonadotropic action of cyproterone, provides an additional therapeutic effect. These changes are reversible after drug withdrawal. When combined with Diane-35, suppression of ovarian function occurs.

Systemic Toxicity

Existing results of preclinical toxicity studies with repeated use of the drug do not imply any specific risk for a person.

Embryotoxicity / teratogenicity

Studies of embryotoxicity showed a teratogenic effect after application of the drug in the period of organogenesis before the development of external genitalia. The intake of high-dose cyproterone during the hormonal-sensitive phase of genital differentiation led to the appearance of feminization signs in male fetuses. Survey of newborn boys, mothers of whom received cyproterone during pregnancy, did not reveal any signs of feminization. The use of Androkur® during pregnancy is contraindicated.

Genotoxicity and carcinogenicity

In the first series of preclinical studies of the genotoxicity of cyproterone, negative results were obtained. However, the ability of cyproterone to form compounds with DNA, incl. increase the activity of DNA repair in liver cells in different animal species and in a freshly prepared culture of human hepatocytes.

Consequences of treatment with cyproterone in vivo female rats had a more frequent occurrence of focal, possibly premalignant, foci in the liver with altered enzyme composition of the cells and an increase in the mutation rate in the transgenic in the bacterial gene of rats.

Clinical experience and carefully conducted epidemiological studies do not confirm an increase in the incidence of liver tumors in humans. Studies on rodents also do not give any indication of the specific oncogenic potential of cyproterone. but it must be borne in mind that sex hormones can induce the growth of certain hormone-dependent tissues and tumors.

Pharmacokinetics:

Absorption

Ciproterone is completely absorbed after ingestion. Absolute bioavailability of cyproterone is about 88%.

Distribution

The maximum concentration of cyproterone in the blood plasma after taking a dose of 10 mg reaches 75 ng / ml on average after 1.5 hours. The half-life of cyproterone is biphasic: the first phase is 0.8 hours, the second - 2.3 days. The total clearance of cyproterone from plasma is 3.6 ml / min / kg.

Ciproterone almost completely binds to albumin plasma. About 3.5 - 4% of cyproterone remains unbound. Since the association with plasma proteins is non-specific, a change in the concentration of globulin binding the sex hormones does not affect the pharmacokinetics of cyproterone.

Metabolism / biotransformation

Cyproterone is metabolized by hydroxylation and conjugation. The main metabolite in the blood plasma is the 15β-hydroxy derivative.

Excretion

It is exposed to biotransformation in the liver, it is excreted mainly as metabolites with bile and kidneys (half-life of 1.9 days) in a ratio of 3: 7, part is excreted unchanged with bile. Metabolism in the blood plasma occurs at the same rate (half-life of 1.7 days).

Cyproterone has a long half-life, which, with daily intake during the cycle, leads to its cumulation and an increase in plasma concentration of 2 to 2.5 times.

Indications:

Manifestations of androgenization of moderate severity in women, such as:

hirsutism of moderate severity;
androgenic alopecia of moderate severity;
severe and moderately severe forms of acne, accompanied by inflammation,
the formation of nodules or the risk of scarring, and seborrhea.

The drug is used as part of a combination therapy with Diane-35 in cases where there is no clinical improvement in response to other treatments and satisfactory results have not been achieved with the use of Diane-35 alone.

Contraindications:

Pregnancy and lactation, liver disease, Dubin-Johnson syndrome, Rotor syndrome, liver tumors (including history), idiopathic persistent jaundice or itching during previous pregnancy, a history of herpes gestationis, cachexia, chronic severe depression, meningioma (including history), thrombosis (arterial and venous) and thromboembolism present or in history (including thrombosis, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, cerebrovascular accident), heavy I have a form of diabetes with diabetic angiopathy, sickle-cell anemia, a deficiency of lactase,lactose intolerance, glucose-galactose malabsorption, detected hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them, vaginal bleeding of unclear etiology, hypersensitivity to any of the components of Androcur®, adolescence (until puberty is complete ).

Contraindications for the use of the Diane-35 preparation, which is prescribed in combination with the Androcur® preparation, should also be considered.

Carefully:

In patients with diabetes mellitus.

Diseases / conditions requiring compliance with the precautionary measures when using Diane-35.

Pregnancy and lactation:

The use of the drug during pregnancy and during breastfeeding is contraindicated.

Dosing and Administration:

To ensure reliable contraception and prevent irregular bleeding, Androkur® is taken in combination with Diane-35.

Admission of both drugs begins on the 1st day of the cycle (that is, on the 1st day of menstrual bleeding).

As a rule, one tablet of Androkur® is taken on a daily basis from the 1st to the 15th day of the treatment cycle in addition to Diane-35.

In the package, each tablet is marked with the day of the week in which it should be taken.Take one tablet of Androcur® and Diane®-35 at the same time each day, with a small amount of water. Follow the direction of the arrow until all 15 Androkur® tablets are taken. In the next 6 days only Diana®-35 is taken.

When after 21 days of admission, the Diana®-35 calendar pack will end, followed by a 7-day break in taking the tablets, during which menstrual bleeding should begin.

After a 7-day break, regardless of whether menstrual bleeding has stopped or is still ongoing, the pill is resumed from the following calendar packs of Androcur® and Diane®-35.

If menstrual bleeding does not occur during the break, which is extremely rare, discontinue treatment and do not resume taking the pills until pregnancy is ruled out.

Acceptance of missed tablets

If the patient has forgotten to take the Diane-35 tablet at the usual time, then this should be done no later than within the next 12 hours. If more than 12 hours have elapsed since the usual Diane-35 administration, the contraceptive effect in this cycle may be weakened.It is necessary to pay attention to special comments concerning contraceptive reliability, as well as recommendations for missed tablets, which are included in the information on the Diane-35 preparation. If after this cycle, menstrual bleeding is absent, pregnancy should be excluded before resumption of pills.

Passing AndroCur® tablets can lead to a decrease in the therapeutic effect and cause menstrual bleeding. The missed drug pill is not taken (i.e., do not take a double dose to compensate for the missed tablet) and resume the drug at the usual time together with the Diane-35 preparation.

The duration of treatment is determined by the doctor depending on the severity of the pathological signs of androgenization and their dynamics during treatment. Drugs should be taken within a few months. The therapeutic effect of acne and seborrhea usually manifests itself more rapidly than with hirsutism and alopecia.

After achieving a clinical improvement, you should try to continue treatment only with Diane-35.

Application in certain categories of patients

Children and adolescence

A study of efficacy and safety in clinical trials involving children or adolescents under the age of 18 was not conducted.

Elderly age

The drug Androkur® is indicated only for women of reproductive age.

Liver failure

The use of Androcur® is contraindicated in patients with liver disease.

Renal insufficiency

There is no data on the need to change the dose in this category of patients.

Side effects:

The most common side effects in patients taking Androcour® 10 mg are spotting from the vagina, weight gain and mood reduction.

The most serious side effect of the drug Androkur® 10 mg is the development of benign and malignant liver tumors that can lead to life-threatening intraabdominal bleeding.

An abdominal discomfort and nausea in patients caused by the action of cyproterone acetate, the active ingredient of the Androkur® 10 mg preparation, has been reported.

The table below lists the side effects of Androcour® 10 mg,based on postmarketing research and cumulative experience, the frequency of which can not be determined.

Organs and Systems	Frequency not defined
Benign, malignant and unspecified neoplasms (including cysts and polyps)	Benign and malignant liver tumors *
Immune system disorders	Hypersensitivity reactions
Metabolic disorders	Decreased body weight, weight gain, hyperglycemia
Disorders of the psyche	Depression, increased libido, decreased libido
Disorders from the gastrointestinal tract	Intraperitoneal hemorrhage *
Disturbances from the liver and bile ducts	Dysfunction of the liver, jaundice, hepatitis
Disturbances from the skin and subcutaneous tissues	Rash
Violations of the genitals and mammary gland	Tension, tenderness and enlargement of the mammary glands, absence of ovulation, acyclic bleeding or absence of menstrual bleeding, spotting from the vagina *

* - for more information, see "Special instructions".

Against the background of combined therapy, the inhibition of ovulation occurs, so there is a condition in which conception is impossible.

Side effects as specified in the Diane-35 preparation instructions should also be considered.

Overdose:

In studies of acute toxicity after a single dose, it was found that cyproterone acetate, the active ingredient in the Androkur® preparation, can be considered to be practically non-toxic. The risk of acute intoxication after a single random dose, several times higher than the recommended therapeutic dose, is unlikely.

Interaction:

Against the background of taking Androkur®, there may be a change in the need for oral hypoglycemic agents or insulin.

Studies related to drug interactions have not been conducted, but since Androcour® is metabolized by the CYP3A4 isoenzyme, it is expected that ketoconazole, itraconazole, clotrimazole, ritonavir and other potent inhibitors of the CYP3A4 isoenzyme will inhibit cyproterone metabolism. And, accordingly, inducers of the isoenzyme CYP3A4, such as rifampicin, phenytoin and preparations containing St. John's wort puffed can reduce the concentration of cyproterone in the blood plasma.

In chronic alcoholism, the use of high doses of the drug may reduce (weakening) the effect of therapy in the treatment of increased sexual desire in men. It is suggested that this may be related to the induction of alcohol by the enzymes involved in the metabolism and excretion of cyproterone. There is no data suggesting a decrease in the therapeutic effect of Androkur® with moderate alcohol use.

Special instructions:

Before the start of treatment, a general medical and gynecological examination (including a breast examination and cytological examination of the cervical epithelium) should be carried out. It is also necessary to exclude pregnancy.

Effects on the liver

During the treatment periodical control of liver function is necessary.

Before the start of treatment, periodically during treatment and when any symptoms or signs of hepatotoxicity appear, it is necessary to perform liver function tests. If the following symptoms occur, you should consult a doctor: general malaise, fever, nausea, vomiting, loss of appetite, pruritus, icteric staining of the skin and sclera, discoloration of the stool, dark color of urine.With confirmed hepatotoxicity, therapy with Androkur® should be discontinued.

Against the background of the use of Androkur®, the development of benign and malignant liver tumors was noted, which can lead to life-threatening intraabdominal hemorrhages. With the increase in the liver, the appearance of severe pain in the upper abdomen or a clinical picture of intra-abdominal bleeding, it is necessary to take into account the possibility of the patient having a liver tumor.

Diabetes

Patients with diabetes may need a dose adjustment for oral hypoglycemic drugs or insulin. Patients with diabetes mellitus during treatment with Androkur® should be supervised by a doctor.

Combined treatment

If the combined therapy during the 3-week period of taking the tablets observed "smearing" bloody discharge, treatment should not be interrupted. However, with persistent or repeated untimely bleeding it is necessary to perform a gynecological examination in order to eliminate the organic disease.

In view of the need for additional administration of Diane-35, all contraindications and all information contained in the instructions for use of Diane-35 should also be considered. The drug Androkur® contains 63 mg of lactose in 1 tablet. Patients with rare hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome should not use this drug.

Absence of bleeding "cancellation"

If menstruation-like bleeding does not occur within 7 days during a break or after discontinuation of the drug, which is extremely rare, discontinue treatment and do not resume taking the pills until pregnancy is ruled out.

Meningioma

The development of meningiomas (single and multiple) has been reported in connection with the long-term (for several years) administration of Androkur® in a dose of 25 mg or more. In the case of diagnosis of meningioma in patients taking Androcur® at a dose of 10 mg, drug treatment should be discontinued.

Effect on the ability to drive transp. cf. and fur:

Studies concerning the impact on the ability to drive a vehicle and other mechanisms have not been carried out.

Form release / dosage:

Tablets 10 mg.

Packaging:

For 15 tablets per blister Al / PVC. One blister along with the instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not higher than 25 ºС.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N016225 / 01

Date of registration:19.02.2010

Expiration Date:Unlimited

The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany

Manufacturer: & nbsp

BAYER WEIMAR, GmbH & Co. KG. KG Germany

Information update date: & nbsp05.09.2017

Illustrated instructions

Instructions

Androkur® (Androcur®)