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

Active substanceDanazolDanazol

Similar drugsTo uncover

Danol®

capsules inwards

Sanofi-Synthelabo Co., Ltd. United Kingdom

Dosage form: & nbspcapsules

Composition:

1 capsule with a dosage of 100 mg contains:

active substance: danazol (micronized) - 100.00 mg;

Excipients: corn starch - 62.00 mg, lactose monohydrate - 62.00 mg, talc - 5.00 mg, magnesium stearate - 1.00 mg.

Capsule shell:

housing: gelatin - 98,000%, titanium dioxide (E 171) - 2,000%; lid: gelatin - 97.599%, titanium dioxide (E 171) - 2,000%, ferric oxide black oxide (E 172) - 0.401%.

Black ink (composition 1): 45% solution of shellac in ethanol - 59.420%, iron dye oxide black (E 172) - 24.650%, butanol * - 9.75%, water * - 3.249%, propylene glycol - 1.300%, ethanol * - 1.080%, isopropanol * 4 0.550%, ammonia water * - 0.001%

or black ink (composition 2): shellac - 24-27%, ethanol * - 23-26%, isopropanol * - 1-3%, butanol * - 1-3%, propylene glycol - 3-7%, ammonia water * - 1-2%, iron oxide dye black (E 172) -24- 28%, potassium hydroxide - 0.05-0.1%, water * - 15-18%.

1 capsule with a dosage of 200 mg contains:

active substance: danazol (micronized) - 200.00 mg;

Excipients: corn starch - 76.60 mg, lactose monohydrate - 76.60 mg, talc - 5.00 mg, magnesium stearate - 1.80 mg.

Capsule shell:

housing: gelatin - 98,000%, titanium dioxide (E 171) - 2,000%; lid: gelatin - 98.217%, titanium dioxide (E 171) - 1.316%, iron dye red oxide (E 172) -0.362%, ferric oxide yellow oxide (E 172) - 0.151%.

Black ink (composition 1): 45% solution of shellac in ethanol - 59.420%, iron dye oxide black (E 172) - 24.650%, butanol * - 9.750%, water * - 3.249%,propylene glycol 1.300%, ethanol 1.080%, isopropanol 0.550%, aqueous ammonia 0.001%, or black ink composition 2: shellac 24-27%, ethanol 23-26%, isopropanol 1 -3%, butanol * 1-3%, propylene glycol 3-7%, ammonia water * 1%, iron dye oxide black (E 172) 24-28%, potassium hydroxide 0.05-0, 1%, water * - 15-18%.

* - Removed during production.

Description:

Capsules 100 mg

Hard gelatinous opaque capsules No. 3, consisting of a white body and a gray lid. The contents of capsules are white or almost white powder. The body and cap of the capsule are marked "D100".

Capsules 200 mg

Hard gelatinous opaque capsules No. 1, consisting of a white body and a brownish-pink lid. The contents of capsules are white or almost white powder. The body and cap of the capsule are marked "D200".

Pharmacotherapeutic group:Gonadotropic hormone secretion inhibitor

ATX: & nbsp

G.03.X.A.01 Danazol

Pharmacodynamics:

Antigonadotropnoe means, which is a synthetic androgen, obtained from etisterona. Suppresses the production of pituitary gonadotrophic hormones of luteotropic hormone (LH) and follicle-stimulating hormone (FSH) in men and women.

Women are depressed by ovarian activity, reduces estrogen levels and blocks estrogen receptors, inhibits ovulation, causes endometrial atrophy.The effect is reversible, the drug is devoid of estrogen or progestational effect, in high doses has a weak androgenic activity with concomitant anabolic effect.

When endometriosis damages both normal and ectopic endometrial tissue, leading to its inactivation and atrophy. Reduces pain syndrome, concomitant endometriosis, causes regressive changes in endometriotic foci. It has an immunosuppressive effect and suppresses the proliferation of lymphocytes in vitro. Significantly reduces the content of immunoglobulins (Ig) and the production of autoantibodies in patients with endometriosis.

With fibrocystic mastopathy contributes to the partial or complete disappearance of nodular seals and complete relief of pain syndrome. Clinical efficacy in hereditary angioedema may be due to an increase in the content of the C1-esterase inhibitor (congenital deficiency is characteristic of this disease) and, as a result, an increase in the plasma content of the C4 complement component.

Pharmacokinetics:

Absorption

The intake of food (fats over 30 g) delays the absorption of danazol by 30 minutes,and increases the bioavailability and maximum concentration in the blood plasma (C_m_Oh). Time to reach C_m_Ohvaries from 2 to 8 hours. When taken in a dose of 100 mg 2 times a day C_m_Oh is 200-800 ng / ml, and when administered at a dose of 200 mg twice a day for 2 weeks C_m_Oh is 250-2000 ng / ml. With an increase in the dose, bioavailability increases, but not in proportion to the increase in dose. When the dose is doubled, the plasma concentration rises by 35-40%.

Distribution

Studies on the distribution with a labeled radioisotope danazol showed its presence in the intestine and stomach, as well as in the adrenal and excretory organs (kidneys, liver). Danazol and its metabolites, excreted with bile, re-absorbed in the intestines, that is, are subjected to intestinal-hepatic recirculation.

Metabolism

Metabolised in the liver, mainly with the formation of etisterone, 17-hydroxymethylethylidone and 2-hydroxymethylethylidone. Other metabolites are detected in the urine in small amounts. None of these metabolites showed antigonadotropic activity.

Excretion

The half-life (T_1/2) is between 4.5 and 29 hours and has great variability in different patients.

Indications:

- Endometriosis: for the treatment of symptoms associated with endometriosis, and / or to reduce the size of foci of endometriosis, the drug can be used in combination with surgical treatment or only as hormonal therapy in patients in whom other treatments are ineffective.

- Fibrous-cystic mastopathy: symptomatic therapy severe pain in the mammary glands and engorgement of the mammary glands. The drug Danol ® should be used only in patients who have ineffective other therapeutic measures, or in patients who are not recommended the use of such therapeutic measures.

- Hereditary angioedema (the drug is used in men and women).

Contraindications:

- Hypersensitivity to danazol or excipients of the drug;

- bVariability;

- PThe period of breastfeeding;

- POrphyria;

- theMeasured or severe hepatic, renal or heart failure;

- PAtomic bleeding from the genital tract, the cause of which is not diagnosed;

- Ra breast, including hormone-dependent;

- aboutthrombotic thrombosis or thromboembolic disease and indication of them in the anamnesis;

- dlactase deficiency, galactose intolerance, glucose-galactose malabsorption (since the preparation contains lactose monohydrate);

- dUp to 18 years of age.

Carefully:

- Diseases of the liver and kidneys of mild severity;

- arterial hypertension and other cardiovascular diseases;

- any conditions that can be exacerbated by fluid retention in the body;

- diabetes;

- polycythemia;

- epilepsy;

- dyslipidemia;

- history of significant and persistent androgenic reactions with previous sex hormone therapy;

- migraine;

- violation of plasma mechanisms of hemostasis.

If you have one of the listed diseases or conditions. Before taking the drug, consult a doctor.

Pregnancy and lactation:

Pregnancy

During pregnancy and during breastfeeding, the use of danazol is contraindicated because of the possibility of virilization of female fetuses. Before starting therapy with danazol, pregnancy should be excluded. Treatment should begin during menstruation. A woman should use an effective nonhormonal method of contraception.If a woman becomes pregnant during treatment, danazol treatment should be discontinued and she should be informed of the potential risk to the fetus.

Breastfeeding period

Theoretically, there is the possibility of developing androgenic effects in breastfeeding children when taking danazol by the mother, so during lactation, either danazol or breastfeeding should be discontinued.

Dosing and Administration:

Inside.

As a rule, the lowest effective doses are used.

Adults: Usually the daily dose is from 200 to 800 mg, it is divided into 2-4 admission.

Treatment endometriosis should begin with a dose of 200 mg per day. The dose may be increased, if necessary, but not more than 800 mg per day. The duration of treatment is usually 3-6 months, but can be increased up to 9 months if necessary.

When fibrocystic mastopathy the initial daily dose should be 300 mg per day, with severe cyclic mastalgia - 200-300 mg per day. Treatment lasts for 3-6 months.

When angioedema the initial dose should be 200 mg, followed by a decrease (in the absence of exacerbations) within 1-3 months to the lowest effective maintenance dose,preventing the development of angioedema. After stopping angioedema, you can try to cancel the treatment.

Side effects:

The undesirable effects listed below are grouped according to organ systems and are given in accordance with the following gradations of their occurrence frequency: very often: (≥ 10%); often: (≥ 1% - <10%); infrequently: (≥ 0.1% - <1%); rarely: (≥ 0.01% - <0.1%); very rarely: (<0.01%, including individual messages); frequency is unknown: (according to available data, it is not possible to establish the frequency of occurrence).

Violations of the blood and lymphatic system

Rarely

Polycythemia, leukopenia, thrombocytopenia.

Rarely

Eosinophilia, spleen peliosis (the formation of large, blood-filled cavities in the body).

Disorders from the metabolism and nutrition

Development or increase insulin resistance and a decrease in glucose tolerance.

Often: increased appetite.

Rarely: fluid retention.

Disorders of the psyche

Often: emotional lability, anxiety, depressive mood, nervousness, changes in libido.

Disturbances from the nervous system

Often: Headache, muscle tremor, fasciculation (involuntary contraction of individual bundles of muscle fibers).

Rarely: Dizziness, rising intracranial pressure.

Rarely: Weighted epilepsy, provoking a migraine attack, carpal tunnel syndrome (a painful sensation in the wrist that arises after a long work on the keyboard, on a typewriter).

Disturbances on the part of the organ of sight

Rarely: Visual impairments, such as blurred vision, difficulty focusing, difficulties with wearing contact lenses and refractive failure, requiring correction.

Hearing disorders and labyrinthine disorders

Rarely: Vertigo.

Heart Disease

Rarely: Palpitation and tachycardia.

There have been reports of cases of myocardial infarction.

Vascular disorders

Often: "Tides" of blood to the skin, mainly the head and upper half of the trunk.

Rarely: Increase in blood pressure. Thrombotic phenomena, including thrombosis sagittal sinus hard the meninges, cerebrovascular thrombosis, as well as arterial thrombosis.

Infringements from respiratory system and organs of the chest and mediastinum

Often: Change (coarsening) of the voice.

Rarely: Interstitial pneumonitis, pleural pain in the chest (a sharp pain in the chest, appearing or worse with deep breathing or coughing).

Disorders from the gastrointestinal tract

Often: Nausea.

Rarely:Pancreatitis.

Rarely: Pain in the epigastric region.

Unknown frequency: vomiting.

Disorders from the liver of the biliary tract

Rarely: Cholestatic jaundice, benign adenoma of the liver

Rarely: Malignant liver tumor and liver pelitis, which were observed with prolonged use of the drug.

Unknown frequency: Hepatocellular affection liver, hepatic insufficiency, hepatocellular jaundice, hepatocellular focal nodular (nodular) hyperplasia.

Disturbances from the skin and subcutaneous tissues

Often: A rash that can be maculopapular, petechial or in the form of purpura and may be accompanied by a fever. Facial edema and photosensitivity.

Acne, seborrhea, hirsutism, hair loss.

Infrequently: Hives.

Rarely: Inflammatory erythematous nodes, a violation of skin pigmentation, exfoliative dermatitis or exudative multiforme erythema.

Disturbances of musculoskeletal and connective tissue

Often: Pain in the back and lower back, muscle cramps, sometimes with increased activity of creatine phosphokinase, pain in the limbs, joint pain and swelling of the joints.

Disorders from the kidneys and urinary tract

Rarely: Hematuria with prolonged use with hereditary angioedema.

Violations of the genitals and mammary gland

Often: Violation of the menstrual cycle, spotting spotting from genital tract in the intermenstrual period, amenorrhea, dryness vagina, irritation of the mucous membrane of the vagina.

Infrequently: Decrease in the size of dairy glands.

Rarely: Hypertrophy of the clitoris.

Rarely: Reduction of spermatogenesis.

General disorders and disorders at the site of administration

Rarely: Weakness.

Impact on laboratory and instrumental data

Increased concentration of glucagon in the blood plasma, increased plasma concentration low-density lipoprotein cholesterol and decreased plasma cholesterol concentration High-density lipoproteins, including all subfractions, decreased plasma concentrations apolipoproteins AI and AII, induction of synthetase of aminolevulinic acid and a decrease in thyroid-binding globulin and thyroxine (T4) with increased capture of triiodothyronine (T3), but without disturbances of thyroid-stimulating hormone concentrations or free thyroxin index.

Often: Weight gain.

Infrequently: Isolated magnification activity of transaminases in blood serum.

Rarely: Increasing the number erythrocytes and platelets in peripheral blood.

Overdose:

Symptoms: headache, dizziness, tremor, convulsions, nausea, vomiting.

Treatment: take measures to reduce absorption of the drug by taking activated charcoal, removing the drug from the gastrointestinal tract by artificially induced vomiting or gastric lavage. Symptomatic therapy.

In connection with the potential for the occurrence of any deferred patients should be under medical supervision.

Interaction:

With anticonvulsants

Danazol can increase plasma concentrations of carbamazepine (suppressing its metabolism) and can affect the response to carbamazepine and on phenytoin. Perhaps a similar interaction with phenobarbital.

With hypoglycemic drugs

Danazol can cause insulin resistance and weaken the action of insulin and oral hypoglycemic drugs.

With indirect anticoagulants

Danazol can potentiate the effect of warfarin. Danazol enhances the effect of indirect anticoagulants coumarinic series and derivatives of indandion (increases the risk of bleeding).

With antihypertensive drugs

Danazol can reduce the effectiveness of antihypertensive drugs.

With cyclosporine and tacrolimus

Danazol can increase plasma concentrations of cyclosporine and tacrolimus, leading to an increase in renal toxicity of these drugs.

With concomitantly taking steroid medications

There is a possibility of interaction between danazol and sex hormones.

With oral contraceptives

Although no specific interaction with oral contraceptives has been identified, it is recommended not to take oral contraceptives simultaneously with danazol.

With alfacalcidol

Danazol can increase the calcemic response to alfacalcidol with primary hypoparathyroidism.

With laboratory functional tests

Treatment with danazol can affect the determination of testosterone and protein concentrations in the blood plasma.

With inhibitors of HMG-CoA reductase (statins)

With the simultaneous use of danazol and statins metabolized by the CYP3A4 isoenzyme, such as simvastatin, atorvastatin and lovastatin, the risk of myopathy and rhabdomyolysis increases.

Special instructions:

Treatment with danazol requires careful monitoring of patients, especially if they have liver and kidney disease; arterial hypertension and / or other cardiovascular diseases, states accompanied by a delay liquid; epilepsy; diabetes mellitus; polycythemia; metabolic disorders of lipoproteins; androgenic reactions with previous sex hormone therapy; migraine.

Treatment with danazol should be discontinued when any adverse event occurs and, in particular, in the following cases:

- virilization (untimely cancellation of danazol increases the risk of irreversible androgenic effects);

- Edema of the nipple of the optic nerve (symptom of a stagnant nipple) headache, visual impairment, or other signs of increased intracranial pressure;

- jaundice or other indication of serious impairment of the liver;

- Thrombosis or thromboembolism.

If it is necessary to repeat the course of treatment, special care should be taken, since at present there is insufficient data on Long-term follow-up of patients after repeated courses.

In the case of danazol, the risk of long-term effects on the human body of 17-alkylated steroids, to which it belongs in its chemical structure, including the development of benign adenomas of the liver, hepatocellular focal nodular (nodal) hyperplasia, liver peliosis (the formation of large, blood cavities) and liver carcinoma.

Data from case-control type epidemiological studies have been combined to study the relationship between endometriosis, endometriosis treatment and ovarian cancer. Preliminary results from these studies suggest that the use of danazol may increase the baseline risk of ovarian cancer in patients treated for endometriosis.

With prolonged treatment (6 months) and repeated courses of treatment, it is recommended to perform ultrasound examination of the pelvic organs and liver (at least 2 times per year).

All patients receiving danazol, requires regular laboratory monitoring, including the determination of liver function parameters and the composition of peripheral blood.

Before beginning treatment, as well as if the nodes in the mammary gland are retained or enlarged during treatment with danazol, hormone-dependent cancer should be excluded, at least through a thorough clinical examination.

Treatment with danazol should be started during menstruation. The use of high doses of danazol prevents ovulation. However, ovulation is possible at low doses, so an effective non-hormonal contraceptive method should be used when taking the drug.

When used in patients with diabetes mellitus, an increase in the dose of insulin and oral hypoglycemic agents may be required.

When using the drug Danol ® should always choose the lowest effective dose of the drug.

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

It is unlikely that danazol may affect the ability to drive vehicles or engage in other potentially dangerous activities. When unwanted reactions from the side of the eye, vestibular disorders or disorders from the nervous system appear, one should refrain from managing vehicles, working with mechanisms and other activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules, 100 mg and 200 mg.

Packaging:

10 capsules are placed in a PVC / Al blister.

For 6 or 10 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014488 / 01

Date of registration:05.11.2008 / 14.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:Sanofi-Synthelabo Co., Ltd.Sanofi-Synthelabo Co., Ltd. United Kingdom

Manufacturer: & nbsp

ZENTIVA, k.s. Czech Republic

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp21.04.2017

Illustrated instructions

Instructions

Danol® (Danol®)