anadrol

The anadrol combined facility which is due components effects, included in its composition. It inhibits secretion of pituitary gonadotropins. The contraceptive effect of the drug is associated with several mechanisms. Estrogen component of the drug is highly effective oral drugs – ethinyl estradiol (a synthetic analog of estradiol, a hormone involved with the corpus luteum in the regulation of the menstrual cycle). Progestogens component is a derivative of 19-nortestosterone – gestodene, superior strength and selectivity of action is not only a natural hormone of the corpus luteum, progesterone, but modern synthetic progestin (levonorgestrel and others.). Due to the high activity of gestodene used in very low dosages in which it does not exhibit androgenic properties and has practically no effect on the lipid and carbohydrate exchanges.
In addition to these central and peripheral mechanisms, preventing maturation able to fertilize the egg, a contraceptive effect is due to reduction in the susceptibility of the endometrium to blastocyst and increasing the viscosity of the mucus in the cervix located, which makes it relatively impenetrable to sperm. In addition to the contraceptive effect of the drug when taken regularly and has a healing effect, normalizes the menstrual cycle and contributing to the prevention of a number of gynecological diseases, including tumoral nature.
Gestodene: Absorption: ingestion rapidly and completely absorbed. After receiving a single dose maximum plasma concentration measured after an hour and is 2-4 ng / ml. The bioavailability of about 99%.Distribution: binds to albumin and globulin, sex hormone binding (SHBG). 1-2% is in the free state, specifically 50-75% associated with SHBG. Increased SHBG due to ethinylestradiol influences the level of gestodene, resulting in an increase associated with SHBG fraction, and reduce the fraction bound to albumin. The volume of distribution of gestodene 0.7-1.4 L / kg. Metabolism: corresponds to the path of steroid metabolism. The average plasma clearance: 0.8-1.0 ml / min / kg. Excretion: blood level is reduced in two stages. The half-life in the terminal phase of 12-20 h. Derived exclusively in the form of metabolites: 60% in urine and 40% – in the faeces. . Metabolites half-life of about 1 day Stable concentration: pharmacokinetics gestodene largely depends on the level of SHBG. Under the effect of ethinyl estradiol in the blood concentration of SHBG increases threefold; when taking the drug daily level of gestodene in plasma increases by three to four times in the second half of the cycle reaches a saturation state. Ethinylestradiol: Absorption: ingestion absorbed quickly and almost completely. Maximum concentration in the blood is measured after 1-2 hours and is 30-80 pg / ml. Absolute bioavailability ≈ 60% of the primary and pre-systemic metabolism conjugation in the liver. Distribution: easily come into contact with blood nonspecific albumin (about 98.5%) and causes an increase in the level of SHBG. The average volume of distribution of 5-18 l / kg. Metabolism is carried out mainly through aromatic hydroxylation with the formation of large amounts of hydroxylated and methylated metabolites are partly free, partly in the form of conjugated (glucuronide and sulfate). Plasma clearance ≈ 5-13 ml / min / kg. Excretion: The concentration in serum decreases in two stages. The half-life time in the second phase of ≈ 16-24 h. Derived exclusively in the form of metabolites in a ratio of 2: 3 in urine and bile. . Time-life metabolites ≈ 1 day stable concentration: Stable concentration is set to the 3-4 day, with the level of ethinyl estradiol by 20% higher than after taking a single dose.

 

Indications
Contraception.

Contraindications

  • pregnancy or suspicion of it;
  • lactation;
  • presence of severe or multiple risk factors for venous or arterial thrombosis, including complicated lesion valvular atrial fibrillation, cerebrovascular disease, or coronary artery; uncontrolled hypertension moderate or severe with BP 160/100 mm Hg or more);
  • precursors thrombosis (including transient ischemic attack, angina), including the anamnesis;
  • migraine with focal neurological symptoms, including the anamnesis;
  • venous or arterial thrombosis / thromboembolism (including deep vein thrombosis of the lower leg, pulmonary embolism, myocardial infarction, stroke) in the current or history, the presence of venous thromboembolism in relatives;
  • major surgery with prolonged immobilization;
  • diabetes (the presence angiopathy);
  • pancreatitis (including history), accompanied by severe hypertriglyceridemia;
  • dyslipidemia;
  • severe liver disease, cholestatic jaundice (including during pregnancy), hepatitis, including history (up to normalization of functional and laboratory parameters, and within three months after the return of these indicators in the norm);
  • jaundice due to taking drugs containing steroids;
  • cholelithiasis now or history;
  • Gilbert’s syndrome, Dubin-Johnson syndrome, Rotor;
  • liver tumors (including in history);
  • severe itching, otosclerosis or progression of otosclerosis during a previous pregnancy or while taking corticosteroids;
  • hormone-dependent malignancies sex, organs and mammary glands (including suspicion on them);
  • vaginal bleeding of unknown etiology;
  • smoking at the age of 35 years (more than 15 cigarettes a day);
  • individual hypersensitivity to the drug or its components.

Precautions
States, increases the risk of venous or arterial thrombosis / embolism: age over 35, smoking, genetic predisposition to thrombosis (thrombosis, iifarkt infarction or cerebrovascular accident at a young age in any of the next of kin); hemolytic uremic syndrome, hereditary angioedema, liver disease; the disease first appeared or worsen during pregnancy, or on the background of the previous use of sex hormones (including porphyria, herpes gestationis, chorea (Sydenham’s disease), Sydenham’s chorea, chloasma); obesity (body mass index over 30 kg / m²), dislipoproteinemia, hypertension, migraine, epilepsy, valvular heart disease, atrial fibrillation, prolonged immobilization, major surgery, surgery on the lower extremities, severe trauma, varicose veins and superficial thrombophlebitis, postpartum (non-lactating women 21 days after delivery, breast-feeding women after the lactation period), the presence of severe depression, including in history, changes of biochemical parameters (activated protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, deficiency of protein C or S, antiphospholipid antibodies, including antibodies to cardiolipin, lupus anticoagulant).
Diabetes is not complicated by vascular disorders, systemic lupus erythematosus (SLE), Crohn’s disease, ulcerative colitis, sickle-cell anemia; hypertriglyceridemia (including family history), acute and chronic liver disease.

Pregnancy and lactation
Use of the drug during pregnancy and during breast-feeding is contraindicated.

Dosing and dose
Take one tablet per day for 21 days, possibly at the same time. Then, making a 7-day break in reception of tablets to resume oral contraception (ie 4 weeks after taking the first pill on the same day of the week). During the 7-day break occurs uterine bleeding as a result of the abolition of the hormone. The first tablet: Admission drug Lindinet 20 should start from the first to the fifth day of the menstrual cycle.The transition from a combined oral contraceptive to the reception of the drug Lindinet 20: The first tablet of the drug Lindinet 20 recommended to be taken after receiving the last gormonsoderzhaschey pills previous preparation, the first day of withdrawal bleeding. Go of the progestogen-containing regimens ( “mini” pill, injection, implant) to the reception of the drug Lindinet 20: transition from “mini” pill can start any day of the menstrual cycle; in the case of the implant – the next day after its removal; in the case of injections -. on the eve of the last injection In the first 7 days of taking the drug Lindinet 20 should be used an additional method of contraception.

Admission drug Lindinet 20 after an abortion in the first trimester of pregnancy: Admission contraceptives can be started immediately after the abortion, with no need to use an additional method of contraception.

Admission drug Lindinet 20 after delivery or abortion in the second trimester of pregnancy: Admission contraceptive can start on day 21-28 after delivery or abortion in the second trimester of pregnancy. At a later start of oral contraceptives, in the first 7 days, you need to apply extra barrier method of contraception. In the case where sexual intercourse had taken place before the beginning of contraception before you start taking the drug, you should exclude the presence of a new pregnancy or wait until the next menstrual period. Missed tablets If the next scheduled appointment has been missed pills, then you should as soon as possible to make up the missed dose. At a delay of no more than 12 hours contraceptive effect of the drug is not reduced, and the need to use an additional method of contraception is not.The remaining tablets taken as usual. With more than 12-hour delay contraceptive effect may be reduced. In such cases, do not make up the missed dose, continue taking the drug as usual, but in the next 7 days is necessary to use an additional method of contraception. If this in the package was less than 7 tablets, then to the reception of the next pack of pills proceed without observing the break. In such cases, uterine withdrawal bleeding occurs only at the end of the second package; while taking tablets from the second package may be spotting or breakthrough bleeding. If at the end of reception of tablets of the second pack of withdrawal bleeding does not occur, then, before you continue receiving contraceptive, should exclude the presence of pregnancy. The measures taken in the case of vomiting and diarrhea: If the first 3-4 hours after taking the pill once there is vomiting, the pill is absorbed completely. In such cases it is necessary anadrol to act in accordance with the instructions described in “Missed pill”. If the patient does not want to deviate from the conventional contraception mode, missed pills should be taken from a different package. Delayed menstruation and acceleration timing of menstruation: In order to delay menstruation to reception tablets from a new package proceed without observing the break. Menstruation can be delayed at will as long as the run out of all tablets out of the second package. When menstruation delay possible breakthrough spotting or uterine bleeding. To the ordinary reception of tablets can return after following a 7-day break. With a view to an earlier onset of menstruation can be shortened 7-day break for the desired number of days. The shorter the interval, the more likely the occurrence of breakthrough bleeding or spotting while taking tablets from the next package (like the case of a delay of menstruation).

 

Side effects Side effects, when they appear, require immediate discontinuation of the drug:

  • arterial hypertension;
  • hemolytic-uremic syndrome;
  • porphyria;
  • loss of hearing due to otosclerosis.

Rare: arterial and venous thromboembolism (incl myocardial infarction, stroke, deep vein thrombosis of the lower extremities, pulmonary embolism); . reactive exacerbation of systemic lupus erythematosusis extremely rare: arterial or venous thromboembolism hepatic, mesenteric, renal, retinal arteries and veins; Sydenham’s chorea (taking place after the drug). Other side effects are less severe, but more common. Whether to continue the drug is solved individually after consultation with the doctor, based on the benefit / risk ratio.

  • Reproductive System: acyclic bleeding / spotting from the vagina, amenorrhea after discontinuation of the drug, the change of state of the vaginal mucus, the development of inflammatory processes of the vagina (eg .: candidiasis), libido change.
  • Mammary glands: stress, pain, breast enlargement, galactorrhea.
  • Gastrointestinal and hepato-biliary system: nausea, vomiting, diarrhea, epigastric pain, Crohn’s disease, ulcerative colitis, hepatitis, hepatic adenoma, emergence or worsening jaundice and / or pruritus related to cholestasis, cholelithiasis.
  • Skin: node / erythema, rash, chloasma, increased hair loss.
  • Central nervous system: headache, migraine, mood changes, depression.
  • Metabolic disorders: fluid retention in the body, a change (increase) of body weight, elevated triglycerides and blood sugar levels, decreased carbohydrate tolerance.
  • Special Senses: hearing loss, increased sensitivity of eyes cornea while wearing contact lenses.
  • Other: allergic reactions.

Overdose
Admission large doses of contraceptive was not accompanied by the development of severe symptoms. Signs of overdose include nausea, vomiting, and in young girls a slight vaginal bleeding. No specific antidote, treatment is symptomatic.

Interaction with other drugs
contraceptive effect of oral contraceptives reduced by concomitant use of rifampicin, frequent breakthrough bleeding and menstrual disorders. This, however, is less studied the interaction there between contraception and carbamazepine, primidone, barbiturates, phenylbutazone, phenytoin, and, presumably, griseofulvin, ampicillin and tetracyclines. During the treatment of the above listed drugs simultaneously with the oral contraceptive recommended an additional contraceptive method (condom, spermicidal gel). After completing the course of treatment using an additional method of contraception should be continued for 7 days, in the case of treatment with rifampicin – for 4 weeks. The interactions related to the absorption of the drug: During diarrhea, decreased absorption of hormones due to enhanced intestinal motility. Any drug, Shortening Time Spent hormonal agents in the colon, resulting in lower concentrations of the hormone in the blood. The interactions associated with the metabolism of the drug: The wall of the intestine: Preparations undergoing sulfation in the intestinal wall like ethinyl estradiol (. Eg ascorbic acid), kompetitivnym by inhibit metabolism ethinyl estradiol and increase bioavailability. Metabolism in liver: Inductors microsomal liver enzymes reduce levels of ethinyl estradiol in the blood plasma (rifampicin, barbiturates, phenylbutazone, phenytoin, griseofulvin, topiramate, hydantoin, felbamate, rifabutin oskarbazepin). Blockers of liver enzymes (itraconazole, fluconazole) increase the levels of ethinyl estradiol in the blood plasma. Effect on intrahepatic circulation: Some antibiotics (. Eg, ampicillin, tetracycline), preventing intrahepatic circulation estrogens reduce levels of ethinyl estradiol in the plasma. The effect on the exchange of other drugs: Blocking liver enzymes or accelerating the conjugation in the liver, primarily reinforcing glucuronidation, ethinylestradiol affect the metabolism of other drugs (eg., cyclosporin, theophylline), resulting in an increase or a decrease in their concentration in the plasma. not recommended simultaneous application of preparations of St. John’s wort (Hypericum perforatum) with Lindinet 20 tablets due to possible reduction of the contraceptive effect of the active substance contraceptive that can be accompanied by the emergence of breakthrough bleeding and unwanted pregnancies. St. John’s wort activates liver enzymes; after discontinuation of drugs Hypericum effect of enzyme induction may last for the next 2 weeks. Concomitant use of ritonavir and the combined contraceptive is accompanied by a decrease in the average value of AUC of ethinyl estradiol by 41%. During treatment with ritonavir it is recommended to use the drug with a high content of ethinyl estradiol or use a non-hormonal method of contraception. Correction may be required when using the dosing regimen hypoglycemic agents, as Oral contraceptives can reduce the tolerance for carbohydrates, increase the need for insulin or oral antidiabetic agents.

Special instructions
Before starting the use of the drug is recommended to collect a detailed family and personal medical history, and subsequently every 6 months. undergo general medical and gynecological examination (gynecological examination, Pap smear study, the study of mammary glands and liver function, control of blood pressure (BP), the concentration of cholesterol in the blood, urine analysis). These studies must be repeated periodically, in connection with the need for timely detection of risk factors and any contraindications.
The drug is a reliable contraceptive drug: Pearl Index (a measure of the number of pregnancies occurring during the use of methods of contraception in 100 women for 1 year) when used correctly is about 0.05. Due to the fact that the contraceptive action of the drug from the beginning of the reception fully manifested by day 14, in the first 2 weeks of taking the medication, it is recommended to additionally use non-hormonal methods of contraception.
In each case, before the appointment of hormonal contraceptives alone are estimated benefits and possible negative effects of their reception. This issue should be discussed with the patient, who after receiving the necessary information to take a final decision on preference hormone or any other method of contraception. The health status of women should be carefully monitored. If during treatment appears or worsens at any of the following conditions / diseases, you need to stop taking the drug and switch to another, non-hormonal methods of contraception:

  • hemostatic system diseases.
  • condition / illness, predisposing to the development of cardiovascular and renal disease.
  • epilepsy
  • migraine
  • the risk of developing estrogen-dependent tumors, or estrogen-dependent gynecological disorders;
  • diabetes not complicated by vascular disorders;
  • severe depression (if depression is associated with impaired tryptophan metabolism, then the purpose of the vitamin B6 correction can be applied);
  • sickle cell anemia, as in some cases (eg, infection, hypoxia), estrogen-containing drugs in this disease can provoke thromboembolic phenomena.
  • the appearance of abnormalities in laboratory tests of liver function assessment.

Thromboembolic disease
Epidemiological studies have shown that there is a connection between the use of oral hormonal contraceptives and an increased risk of arterial and venous thromboembolic disease (including myocardial infarction, stroke, deep vein thrombosis of the lower extremities, pulmonary embolism). Proved an increased risk of venous thromboembolic disease, but it is significantly less than during pregnancy (60 per 100 thousands of pregnant). When using oral birth control pills are very rare in the arterial or venous thromboembolism hepatic, mesenteric, renal vessels or vessels of the retina.
The risk of arterial or venous thromboembolic disease increases:

  • with age;
  • when smoking (heavy smoking and age older than 35 years are risk factors);
  • if there is a family history of thromboembolic disease (eg, parents, brother or sister). If you suspect a genetic predisposition, it is necessary before applying the medication to consult with a specialist.
  • obesity (body mass index greater than 30 kg / m2);
  • when dislipoproteinemia;
  • with hypertension;
  • in diseases of the heart valves, anadrol complicated by hemodynamic compromise,
  • atrial fibrillation;
  • diabetes mellitus complicated by vascular lesions;
  • with prolonged immobilization, after a big surgery, after surgery on the lower limbs after a serious injury.

In these cases it is assumed temporary cessation of the drug:. It is desirable to terminate no later than 4 weeks prior to surgery, and renew – not earlier than 2 weeks after remobilization
increases the risk of venous thromboembolic disease in women after childbirth.
Diseases such as diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn’s disease, ulcerative colitis, sickle cell anemia, increase the risk of venous thromboembolic disease.
These biochemical abnormalities as resistance to activated protein C, giperhromotsisteinemiya deficit with proteins, S, deficiency of antithrombin III of, the presence of antiphospholipid antibodies increase the risk of arterial or venous thromboembolic disease.
in assessing the benefit / risk ratio of the drug must be borne in mind that the targeted treatment of this condition reduces the risk of thromboembolism.
Symptoms of thromboembolism include:

  • sudden chest pain that radiates to the left arm,
  • sudden shortness of breath,
  • Any unusually severe headache, which lasts a long time or appearing for the first time, especially when combined with the sudden total or partial loss of vision, or diplopia, aphasia, dizziness, collapse, focal epilepsy), weakness or severe numbness in half of the body, movement disorders, severe unilateral pain gastrocnemius muscle, acute abdomen).

Neoplastic Diseases
Some studies have reported a quickening of cervical cancer in women who took a long time, hormonal contraceptives, but research results are contradictory. In the development of cervical cancer play an important role sexual behavior, infection with human papilloma virus, and other factors. Meta-analysis of 54 epidemiological studies showed that there is a relative increase in the danger of breast cancer among women taking oral hormonal contraceptives, but a higher detection rate of breast cancer could be related to more regular medical examination. Breast cancer is rare in women younger than 40 years, regardless of whether they are taking hormonal contraceptives or not, and increases with age. Receiving tablets can be regarded as one of many risk factors. However, women should be advised of the possible risk of cancer of breast, based on the evaluation of the ratio of benefits and risks (from ovarian cancer protection, endometrial and colon).
There are a few reports on the development of benign or malignant liver tumors in women, long-term taking hormonal contraceptives. It should be borne in mind in the differential-diagnostic evaluation of abdominal pain, which may be associated with an increase in liver size or intraperitoneal bleeding.
It is necessary to warn the woman that the drug does not protect against HIV infection (AIDS) and other diseases, sexually transmitted diseases. The effectiveness the drug can be reduced under the following circumstances: . missed pills, vomiting and diarrhea, the simultaneous use of other drugs that reduce the effectiveness of birth control pills If the patient at the same time taking other drugs that may reduce the effectiveness of birth control pills, you should use additional methods of contraception. The efficacy of the drug can be reduced if the after a few months of their application appear irregular spotting or breakthrough bleeding, in such cases it is advisable to continue taking pills until their completion in the next pack. If at the end of the second cycle menstrualnopodobnoe bleeding begins or acyclic bleeding does not stop, stop taking the tablets and to resume it only after the exclusion of pregnancy. Chloasma Chloasma may occasionally occur in those women with whom she had a place in history during pregnancy. Those women who have a risk of chloasma, it is necessary to avoid exposure to sunlight or ultraviolet light while taking the pills. Changes in laboratory parameters Under the influence of oral contraceptive pills – due to the estrogen component – may change the levels of certain laboratory parameters (liver function indexes, renal, adrenal, thyroid, hemostasis, levels of lipoproteins and transport proteins). After acute viral hepatitis should be taken after normalization of liver function (no earlier than 6 months). When diarrhea or intestinal disorders, vomiting contraceptive effect may decrease (without stopping taking the drug, it is necessary to use additional non-hormonal methods of contraception). Women who smoke have an increased risk of developing cardiovascular disease with serious consequences (myocardial infarction, stroke). The risk depends on the age (especially in women older than 35 years) and the number of cigarettes smoked. During the period of lactation may reduce the milk in small quantities component drug is excreted in breast milk. testosterone cypionate