2010/06/07

TRISTIN

Pharmacological properties: combined oral contraception drug works by blocking gonadotropin. The primary effect is to prevent ovulation. Other effects, such as changing the properties of cervical mucus (preventing the penetration of sperm into the uterus), endometrial changes (difficulty of implantation) also impede conception.

Gestoden

When administered quickly and almost completely absorbed. Bioavailability - 100%. The maximum concentration is achieved within 30 min after administration and is 19 micrograms per liter.

Gestoden bound to albumin and globulin, sex hormone binding (SHBG). Only 0,5-1% gestodena is in a free state, 75-87% - specifically binds to SHBG. Increased SHBG caused by ethinylestradiol affects the level of gestodena, leading to an increase in the faction associated with SHBG and a decrease associated with the albumin fraction. Apparent volume of distribution - 17-19 liters.

Gestoden completely metabolized. Its metabolism corresponds metabolic pathways of steroids.

Clearance - 0,01 l / h / kg. Gestodena concentration in blood plasma is reduced in two stages. The half-life in the second phase - about 20-22 hours Gestoden derived exclusively as metabolites in the urine and bile in the ratio 6:4. The half-life - about 1 day.

Ethinylestradiol

When administered quickly and almost completely absorbed. Absolute bioavailability due presistemnoy conjugation and primary metabolism in the liver is about 38-48%.

Ethinylestradiol firmly, but not specific bound to albumin of blood plasma (approximately 98,5%) with higher levels of SHBG. The apparent mean volume of distribution - 2-4 L / kg.

The collapse of ethinyl estradiol occurs mainly through presistemnoy conjugation. In the intestinal phase I metabolism occurs, as in the liver by conjugation (II phase of metabolism). The most important metabolites of phase I: 2-OH-ethinylestradiol and 2-methoxy-ethinylestradiol. How ethinylestradiol and its metabolites of phase I, conjugates with sulphate and glucuronide and after enterohepatic circulation derived from bile. The half-life - 26 ± 6,8 h.

The concentration of ethinylestradiol in blood plasma decreases in two stages. Ethinylestradiol appears exclusively in the form of metabolites at a ratio of 2:3 in the urine and bile.

INDICATIONS: oral contraception.

Directions: Take 1 tablet a day for 21 days, possibly in the same time of day. The following 21 tablet should be taken after a 7-day interval, ie 4 weeks after receiving the first pill on the same day of the week. During the 7-day break there bleeding associated with the abolition of hormones.

Receiving the first pill

Receiving the first pill Tristin should begin on the first day of the menstrual cycle.

Moving from another combined oral contraceptive to receive Tristin

Tristin pills should be started after taking the last gormonsoderzhaschey tablets from the packaging of the drug in the previous first day of bleeding associated with the elimination of the drug.

The transition from progestagensoderzhaschih preparations (mini-pills, injections, implants) on pills Tristin

The transition from mini-pills to tablets Tristin can start any day of the menstrual cycle. In the case of implant - the day after his removal, but in the case of injections - before the next injection.

At the same time during the first 7 days of pills Tristin is necessary to use an additional method of contraception.

Tristin pills after abortion in the I trimester of pregnancy

Tablets you can start immediately after abortion. In this case there is no need to use an additional method of contraception.

Tristin pills after childbirth or after an abortion in the II trimester of pregnancy

Tristin pills can start at the 28 th day after birth or abortion in the II trimester of pregnancy. At the same time during the first 7 days of pills Tristin is necessary to use an additional method of contraception.

If the sexual contact occurred after childbirth or abortion before the start of contraception, it should exclude the presence of pregnancy or wait until the first menstruation.

Missed pills

If you receive a regular tablet is missed, it should be as early as possible to take the missed dose. At a delay of up to 12 hours, contraceptive efficacy is not reduced, thus no need to use additional methods of contraception. The other tablets should be taken in normal mode.

If the delay exceeds 12 hours, contraceptive efficacy is reduced. In this case, should not be missed (-WIDE) tablet (s), and continue taking the drug in normal mode, but in the next 7 days is necessary to use additional methods of contraception. If the package was less than 7 pills, the tablets to receive the next pack should proceed without interruption. This bleeding associated with the elimination of the drug is absent and appears only after taking the tablet from the second package. During the tablets from the second package may be breakthrough bleeding or mazhuschee.

If, after taking pills from the second pack withdrawal bleeding does not occur, before continuing the contraceptive method should exclude the presence of pregnancy.

Measures taken in case of vomiting and diarrhea

If in the first 3-4 h after pills develops vomiting, the tablet is not fully absorbed. Diarrhea increases the motility and impairs the absorption of hormones. In this case, you should take another pill. If the patient does not wish to deviate from the usual regimen of the drug, it is necessary (-mye) tablet (s) should be taken from other packages.

CONTRAINDICATIONS: combined contraceptive drugs should not be taken in the following cases:

diagnosed currently or in history: venous thrombosis (eg deep vein thrombosis, thromboembolism of the pulmonary vessels), arterial thrombosis (such as thrombosis or thromboembolism of the cerebral vessels), or predisposing conditions to them (such as angina, transient ischemic attacks).

The presence of multiple or severe risk factors predisposing to the development of arterial thrombosis:

diabetes mellitus with angiopathy, severe or uncontrolled hypertension, marked dyslipoproteinemia.

The presence of inherited or acquired biochemical changes indicative of a predisposition to develop venous or arterial thrombosis, such as resistance to activated protein C (APC-resistance), antithrombin III deficiency or protein C and S, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) .

Available now or a history of severe liver disease before the normalization of liver function, benign or malignant tumor of the liver.

Known, estimated or appearing in history: malignant tumor of the breast, malignant tumors estrogenzavisimye.

Vaginal bleeding of unknown etiology.

Specifying a history of a headache with focal neurological symptoms, herpes during pregnancy.

Hypersensitivity to any component of the drug.

SIDE EFFECTS:

Infection: fungal infection of the vagina.

Benign and malignant tumors (including cysts and polyps): adenoma of the liver.

Mental disorders: depressed mood.

Of the nervous system: headache.

From the side of view: the discomfort while wearing contact lenses.

Vascular disorders: thromboembolism.

From the gastrointestinal tract: nausea, vomiting and diarrhea.

On the part of the hepatobiliary system: gallbladder disease, hepatitis, jaundice.

Changes in skin and subcutaneous fatty tissue: skin rashes, chloasma, hair loss.

From the breast and reproductive system: breast engorgement, libido change, change of vaginal secretion, mazhuschie bleeding, menstrual irregularities.

General: poor health, fatigue.

The results of instrumental and diagnostic studies: loss of glucose tolerance, weight change, increased levels of TG and glucose in the blood serum, AH.

Cautions: pills Tristin is contraindicated in pregnancy, so before the admission of oral contraceptives should be deleted its presence. In the event of pregnancy receiving the drug should be stopped immediately.

Evidence from several epidemiological studies have shown that newborns whose mothers took oral contraceptives prior to becoming pregnant, did not observe any increase in the frequency of violations of, or manifestation of teratogenic effects (especially congenital malformations of the heart and limbs), even in cases where the drug is used in the early stages pregnancy.

The use of oral contraceptives during lactation is not recommended because of their ability to reduce the secretion of milk, change its composition and in small amounts penetrate into the milk.

Before and during or before receiving contraceptive continuation after the break, it is necessary to conduct a periodic medical examination (detailed medical history, and spreads to other family members, a thorough gynecological examination with inspection of the mammary glands and organs in the abdominal cavity, the measurement of blood pressure, cytological analysis, undertake relevant laboratory studies). Furthermore, it should exclude the presence of pregnancy.

Women taking oral contraceptives should be informed that the pill does not protect against HIV infection or other diseases, sexually transmitted infections.

Diseases of circulatory

Venous and arterial thrombosis and thromboembolism

These epidemiological studies confirm the link between the use of combined oral contraceptives and the development of venous or arterial thromboembolic events, including myocardial infarction, cerebrovascular disease (ischemic and hemorrhagic stroke), deep vein thrombosis and pulmonary embolism.

All combined oral contraceptives increase the risk of venous and arterial thrombosis or thromboembolism in patients taking such drugs, compared with those, they are not receiving.

The risk of venous thromboembolic disease (VTZ) higher among those taking combined oral contraceptives. In the first year of contraception VTZ risk is particularly high among women who had never taken the combined oral contraceptives. However, this risk is lower than that associated with pregnancy (60 cases per 100 000 pregnancies, while 2.1% VTZ are fatal).

VTZ developed less if the content of ethinyl estradiol tablet below 50 mg in combination with levonorgestrel (20 sluchaev/100 000 patient-years). The incidence of VTZ-makers combined preparations containing gestoden, 30-40 sluchaev/100 000 patient-years. Increased risk in the first year the drug is particularly high among women who never took combined oral contraceptives.

Increase the risk of arterial or venous thromboembolic disease contribute to age, smoking (compulsive smoking and age over 35 years, exacerbating the risk, in which case you must completely give up smoking), weighed down by family history (eg thromboembolism parents or sisters and brothers at a young age); obesity (body mass index> 30 kg / m 2), dyslipoproteinemia, hypertension, valvular heart disease, atrial fibrillation (atrial fibrillation), prolonged immobilization, major surgery, operations on the lower extremities, severe trauma. Since the risk of thromboembolism in the postoperative period increases, for 4 weeks before the planned operation should temporarily stop taking the contraceptive. Continued receiving contraceptive is recommended after 2 weeks after complete remobilization of gold.

If signs of thrombosis (chest pain radiating to his left hand, unusually severe pain or swelling of the lower extremities, stabbing pain when coughing or during a breath, blood in the sputum) should immediately stop taking birth control pills.

In the presence of congenital or acquired biochemical parameters, indicating a predisposition to venous or arterial thrombosis: resistance to activated protein C (APC-resistant), hyperhomocysteinemia, deficiency of antithrombin III, or protein C and S, and the presence of antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant ) - taking the drug is invalid.

Effect on blood pressure

There have been cases BP increase in use of oral contraceptives, especially among older women and among those taking oral contraceptives long.

More likely to develop hypertension when taking drugs with a high content of hormones.

Women with a history of hypertension or diseases which are accompanied by hypertension, as well as kidney problems, is not recommended to take oral contraceptives. If, despite this, the patient with hypertension decides to take oral contraceptives, then it should be regularly monitored and significant increase in blood pressure medication should be abolished. For most women, blood pressure to normal after stopping oral contraceptives in the future fact of receiving contraceptive history does not affect the development of hypertension.

Tumors

Some studies have described increased frequency of cervical cancer in women, a long time taking the pill, but these results are contradictory. The development of cervical cancer also affects sexual behavior and other factors (such as human papilloma virus).

Meta-analysis of 54 epidemiological studies showed that the relative risk of developing breast cancer increases among women taking oral contraceptives (relative risk = 1.24). This risk gradually decreases in the 10 years after discontinuation of contraceptive. However, these subsequent studies have not confirmed a causal link.

Persons taking contraceptives, revealed cases of breast cancer in earlier clinical stage than those who did not take contraceptives.

Known rare cases of benign liver tumors in women taking oral contraceptives. The gap of the tumor may be associated with fatal or life-threatening intraperitoneal bleeding.

In rare cases, women who for a long time taking oral contraceptives, noted the development of malignant tumors of the liver.

Other pathological conditions

In rare cases, against the background of the reception of oral contraceptives may develop thrombosis retina. Acceptance of the drug should be discontinued when complete or partial loss of vision, exophthalmos, diplopia, edema of the optic nerve papilla or vascular lesions of the retina.

According to earlier studies among women taking contraceptives or estrogensoderzhaschie drugs increases lifetime relative risk of gallstone. According to the latest use of drugs with a low dose of hormones is accompanied by a low risk of stone formation in gall bladder.

If you or a worsening of the migraine or the development of unusually intense, repeated or persistent headache receiving the drug should be discontinued.

When a generalized itching or developing an epileptic seizure pills Tristin should cease immediately.

Effect on exchange of fats and carbohydrates

In women taking oral contraceptives, in some cases may decrease glucose tolerance. Therefore, patients with diabetes mellitus during the reception of oral contraceptives should be regularly monitored.

In some cases, receiving oral contraceptives was accompanied by hypertriglyceridemia. Many progestogens reduce the level of HDL in plasma. Because estrogen increases the level of HDL in the blood plasma, the effect of contraceptives on lipid depends on the ratio of estrogen and progestogen them, as well as the type and amount of progestogen.

Patients with hyperlipidaemia who do decide to take contraceptives, should be regularly monitored.

In women with a family hyperlipidemia taking estrogen-containing medications may significantly increase the level of TG and the subsequent development of pancreatitis.

Violation of the menstrual cycle

While receiving oral contraceptives, especially in the first three months, there may be irregular or breakthrough bleeding mazhuschie.

The appearance of long irregular bleeding or bleeding after regular menstruation indicates the non-hormonal nature of bleeding and requires a gynecological examination to exclude cancer or pregnancy. After excluding non-hormonal causes should move to another birth control pills.

In some cases, 7-day break in contraception is not accompanied by bleeding associated with the elimination of the drug. If the contraceptive method was carried out not by the scheme or after receiving all the tablets from the next pack the bleeding is still lacking, then the subsequent reception of the drug can be continued only after the exclusion of pregnancy.

States that require caution while taking the drug

Liver function

In acute and chronic disorders of liver function should stop taking the drug to the full normalization of liver function. If abnormal liver function may be in breach of metabolism of steroids.

Affective disorders

In the case of depression during treatment with contraceptives should stop taking the drug and temporarily switch to another method of contraception in order to identify a causal relationship between depression and contraceptives. Require special attention, women with depression in history. In the case of relapse should stop taking oral contraceptives.

The level of folic acid

Birth control pills may lower levels of folic acid deficiency is clinically has a value only in cases when pregnancy occurs shortly after taking contraceptive.

Other states

Also, special attention should be given a patient with otosclerosis, multiple sclerosis, epilepsy, a small choir, intermittent porphyria, tetany, renal failure, obesity, systemic lupus erythematosus, uterine myoma.

The risk of deterioration melanoderma (chloasma) often is an irreversible process, decreases the exclusion of excessive insolation.

This drug has no effect on ability to drive vehicles or other mehzanizmami.

INTERACTIONS: Due to the interaction with other substances ethinyl estradiol concentration of this hormone in blood plasma may increase or decrease.

Low levels of ethinyl estradiol in the blood plasma increases the frequency of breakthrough bleeding and menstrual disorders, and may also reduce the efficacy of the drug Tristin. When the joint application of preparations containing ethinylestradiol with substances capable of lowering levels of ethinyl estradiol in the blood plasma, it is recommended to resort to other non-hormonal methods of contraception (eg condoms or spermicides). Additional non-hormonal contraceptive methods should be applied throughout the period of taking this drug and for the next 7 days after treatment. If you take rifampicin additional contraceptive method should be used within 4 weeks after receiving rifampicin.

Interaction with drugs which lower the level of contraceptive in the blood plasma (reduce contraceptive effect)

Rifampicin, barbiturates, fenilbutazon, phenytoin, griseofulvin, topiramate, ampicillin, tetracycline.

We do not recommend the simultaneous use of tablets Tristin and drugs from St. John's wort, as the latter degrade the effectiveness of the contraceptive action of the contraceptive. This is due to the fact that St. John's wort induces hepatic microsomal enzymes - induction persists for 2 weeks after drug withdrawal St. John's wort.

The simultaneous use of ritonavir and combined contraceptive is accompanied by a decrease in the average AUC of ethinyl estradiol by 41%. Therefore, during ritonavir is recommended to use drugs with a higher content of ethinyl estradiol or other non-hormonal methods of contraception.

Interaction with drugs that increase levels of ethinyl estradiol in the blood plasma

Atorvastatin

Drugs that are competitive inhibitors sulfatatsii in the gut (for example ascorbic acid (vitamin C) and paracetamol).

Drugs that block 3A4 isoenzymes of cytochrome P450 (such as fluconazole, itrokonazol).

Effect on metabolism of other drugs

Ethinylestradiol may affect the metabolism of other drugs by blocking the liver enzymes, or speeding conjugation in the liver (primarily increasing glyukuronirovanie). As a result, the level of other drugs in blood plasma increased or decreased (eg cyclosporine, theophylline).

Changes of laboratory parameters

Oral contraceptives may distort the results of some laboratory parameters (liver function, thyroid, adrenals, kidneys, levels of transport proteins, lipoproteins, parameters of carbohydrate metabolism, blood coagulation and fibrinolysis). Despite this, laboratory parameters remained within normal limits.

OVERDOSE: receiving high-dose oral contraceptives is not accompanied by the development of serious symptoms.

Symptoms of overdose: nausea, vomiting, young girls - some vaginal bleeding. There is no specific antidote, treatment is symptomatic.

Storage conditions: at a temperature of 15 - 25 ° C.