Regulon

Active material: Desogestrel, Ethinylestradiol
When ATH: G03AA09
CCF: Monophasic oral contraceptive
ICD-10 codes (testimony): Z30.0
When CSF: 15.11.04.01
Manufacturer: GEDEON RICHTER Ltd. (Hungary)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated white or nearly white, round, lenticular, labeled “P8” on one side and “RG” – another.

Excipients: a-токоферол, magnesium stearate, colloidal silicon dioxide, stearic acid, povidone, potato starch, lactose monohydrate.

The composition of the coating film: propylene glycol, macrogol 6000, gipromelloza.

21 PC. – blisters (1) – packs cardboard.
21 PC. – blisters (3) – packs cardboard.

Pharmacological action

Monophasic oral contraceptive. The main contraceptive effect is to inhibit the synthesis of gonadotropins and inhibit ovulation. Besides, by increasing the viscosity of cervical mucus slows the movement of the sperm through the cervical canal, a change in the state of the endometrium inhibits implantation of a fertilized egg.

Ethinylestradiol is a synthetic analog of the endogenous estradiol.

Desogestrel has a strong anti-estrogen and progestin action, podobnыm endogenously progesterone, weak androgenic and anabolic activity.

Regulon has a beneficial effect on lipid metabolism: It increases the concentration of HDL in the blood plasma, not affecting the content of LDL.

Before the drug significantly reduced menstrual blood loss (when the original menorrhagia), normal menstrual cycle, It noted a beneficial effect on the skin, especially in the presence of acne vulgaris.

Pharmacokinetics

Desogestrel

Absorption

Desogestrel is rapidly and almost completely absorbed from the gastrointestinal tract and immediately metabolized to 3-keto-desogestrel, which is the biologically active metabolite of desogestrel.

C_max achieved through 1.5 h and is 2 ng / ml. Bioavailability – 62-81%.

Distribution

3-keto-desogestrel is bound to plasma proteins, mainly to albumin and globulin, sex hormone binding (SHBG). V_d is 5 l / kg. C_ss It is set to the second half of the menstrual cycle. Level 3-keto-desogestrel increases 2-3 times.

Metabolism

Additionally 3-keto-desogestrel (which is produced in the liver and gut wall) Other metabolites are formed: 3a-ОН-дезогестрел, 3b-ОН-дезогестрел, 3a-ОН-5a-Н-дезогестрел (metabolites Phase). These metabolites have pharmacological activity and are partially, by conjugation (The second phase of metabolism), converted into polar metabolites – sulfate and glyukwronatı. Clearance from plasma – about 2 ml / min / kg body weight.

Deduction

T_1/2 3-keto-desogestrel is 30 no. The metabolites are excreted with urine and faeces (in relation to 4:6).

Ethinylestradiol

Absorption

Ethinyl estradiol is rapidly and completely absorbed from the gastrointestinal tract. C_max achieved through 1-2 hours after drug administration and is 80 pg / ml. The bioavailability of the drug due presistemna conjugation and effect “first pass” through the liver is about 60%.

Distribution

Ethinyl estradiol is completely bound to plasma proteins, primarily, albumin. V_d is 5 l / kg. C_ss set to 3-4 Day reception, with ethinyl estradiol level in serum on 30-40% higher, than after a single dose of the drug.

Metabolism

Ethinyl estradiol significant first pass conjugation. Passing the intestinal wall (The first phase of metabolism) it is subjected to conjugation in the liver (The second phase of metabolism). Ethinyl estradiol and its conjugates Phase metabolism (sulfate and glucuronide) excreted in the bile and enter the enterohepatic circulation. Clearance from the blood plasma of about 5 ml / min / kg body weight.

Deduction

T_1/2 ethinyl estradiol averages about 24 no. About 40% excreted in the urine and about 60% – with feces.

Testimony

- Contraception.

Dosage regimen

The drug is prescribed inside.

Taking the pills are starting from the 1st day of the menstrual cycle. Assign 1 tab. / day for 21 day, as much as possible at one and the same time of day. After taking the last pill of the box makes the 7-day break, during which bleeding occurs menstrualnopodobnoe due to discontinuation of the drug. On the next day after a 7-day interval (through 4 weeks after the first tablet, on the same day of the week) renew the drug from the following package, also containing 21 tab., even if the bleeding has not stopped. Such a regimen of pills hold until, yet there is a need for contraception. Subject to the rules of admission, the contraceptive effect lasts and a 7-day break.

First intake of the drug

Receiving the first tablet should be started from the first day of the menstrual cycle. In this case, you do not need to use additional methods of contraception. Pills and can start with 2-5 day of menstruation, but in this case in the first cycle of use of the drug is necessary to apply additional methods of contraception during the first 7 the day of taking the pills.

If more than 5 days after the beginning of menstruation, should delay the start of the drug before the next menstrual period.

Taking the drug after birth

Do not breast-feeding women may begin no earlier than pills 21 days after birth, after consultation with the doctor. In this case there is no need to use other methods of contraception. If after birth already had sexual contact, while pills should be postponed until the first menstruation. If a decision on the admission of the drug later, than 21 day after birth, then in the first 7 the day you want to use additional methods of contraception.

Taking the drug after an abortion

After abortion, in the absence of contraindications, start taking the tablets should be from the first day after surgery, and in this case there is no need for additional contraceptive.

Switching from another oral contraceptive

When switching from another oral preparation (21- or 28-day ): first pill Regulon recommended to take the next day after completion of a 28-day drug packaging. After completion of the 21-day course must make a 7-day break and then begin to receive Regulon. No need to use additional methods of contraception.

Go to Regulon after using oral hormonal drugs, containing only progestin (“minipill”)

The first tablet should be taken Regulon in the 1st day of the cycle. No need to use additional methods of contraception.

If the reception “minipill” there is no menstruation, after exclusion of pregnancy, you can start taking Regulon any day of the cycle, but in this case the first 7 days necessary to apply additional methods of contraception (the use of the cervical cap with spermicide gel, Condom, or abstinence from sex). Application calendar method in these cases it is recommended.

Postponement of the menstrual cycle

If there is a need to postpone menstruation, we need to continue taking pills from a new package, 7 days without interruption, in the usual way. With the postponement of menstruation may occur breakthrough bleeding or spotting, but it does not reduce the contraceptive effect of the drug. Regular intake regulon can be restored after the usual 7-day break.

Missed pills

If a woman has forgotten to take the pill in a timely manner, and after passing passed no more 12 no, forgotten to take the pill, and then continue taking the usual time. If passed between taking the tablets better 12 no – it is considered skipping pills, the reliability of contraception in the cycle is not guaranteed and it is recommended to use additional methods of contraception.

When skipping a pill the first or second week of the cycle, be taken 2 tab. the next day, and then continue the regular intake, using additional methods of contraception until the end of the cycle.

Omitting pill the third week of the cycle we must take the forgotten pill, continue regular intake and do a 7-day break. It is important to remember, that in connection with a minimum dose of estrogen increases the risk of ovulation, and / or bleeding in the missed pills and so it is advisable to use additional methods of contraception.

Vomiting / nausea

If after taking the drug appears vomiting or diarrhea, then the absorption of the drug may be defective. If the symptoms ceased for 12 no, it is necessary to take another pill further. After that you should continue taking the tablets in the usual way. If vomiting or diarrhea continues longer 12 no, it is necessary to use additional methods of contraception during vomiting or diarrhea and subsequent 7 Nights.

Side effect

Side effects, requiring discontinuation of the drug

Cardio-vascular system: arterial hypertension; rarely – arterial and venous thromboembolism (v.t.ch. myocardial infarction, stroke, deep vein thrombosis of the lower limbs, pulmonary embolism); rarely – arterial or venous thromboembolism liver, mesenteric, kidney, retinal arteries and veins.

From the senses: hearing loss, due to otosclerosis.

Other: hemolytic uremic syndrome, porphyria; rarely – Reactive worsening of systemic lupus erythematosus; rarely – Huntington Sidenhema (passing after drug withdrawal).

Other side effects are more common, but less severe. Desirability of the continuation of the drug is solved individually after consultation with the doctor, based on the benefit / risk ratio.

On the part of the reproductive system: acyclic bleeding / spotting from the vagina, amenorrhea after discontinuation of the drug, change in the state of vaginal mucus, the development of inflammation of the vagina, candidiasis, voltage, pain, breast enlargement, galactorrhea.

From the digestive system: nausea, vomiting, Crohn's disease, yazvennыy colitis, emergence or worsening jaundice and / or pruritus, associated with cholestasis, cholelithiasis.

Dermatological reactions: uzlovataya эritema, erythema, rash, chloasma.

CNS: headache, migraine, mood lability, depression.

On the part of the organ of vision: increased sensitivity of the cornea (while wearing contact lenses).

Metabolism: fluid retention, change (increase) body weight, reduced tolerance to carbohydrates.

Other: allergic reactions.

Contraindications

- The presence of severe and / or multiple risk factors for venous or arterial thrombosis (incl. hypertension severe or moderate with BP ≥ 160/100 mmHg.);

- An indication of the presence or a history of thrombosis precursors (incl. tranzitornaya ishemicheskaya attack, angina);

- Migraine with focal neurological symptoms, incl. history;

- Venoznыy or arteryalnыy thrombosis / tromboэmbolyya (incl. myocardial infarction, stroke, deep vein thrombosis shin, pulmonary embolism) in the present or past;

- The presence of venous thromboembolism;

- Diabetes (with angiopathy);

- Pancreatitis (incl. history), accompanied by severe hypertriglyceridemia;

- Dyslipidaemia;

- Severe liver disease, cholestatic jaundice (incl. Pregnancy), hepatitis, incl. history (to the normalization of functional and laboratory parameters and within 3 months after the normalization of their);

- Jaundice while taking corticosteroids;

- Gallstone disease now or in history;

- Gilbert's syndrome, Dubin-Johnson syndrome, Rotor syndrome;

- Liver tumors (incl. history);

- Severe itching, otosclerosis or progression during a previous pregnancy or GCS;

- Hormone-dependent malignancies genitals and mammary glands (incl. for suspected them);

- Vaginal bleeding of unknown etiology;

- Smoking age 35 years (more 15 cigarettes per day);

- Pregnancy or suspected it;

- Lactation;

- Hypersensitivity to the drug.

FROM caution should be prescribed for conditions, increase the risk of venous or arterial thrombosis / embolism: older than 35 years, smoking, family history, obesity (body mass index 30 kg / m²), dyslipoproteinemia, arterial hypertension, migraine, epilepsy, valvular heart disease, fibrillyatsiya predserdiya, prolonged immobilization, major surgery, surgery of the lower limbs, severe injury, varicose veins and superficial thrombophlebitis, postpartum, the presence of severe depression (incl. history), changes in biochemical parameters (Activated protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, deficiency of protein C or S, antiphospholipid antibodies, incl. antibodies to cardiolipin, incl. volchanochnyi anticoagulant), diabetes, not complicated by vascular disorders, SLE, Crohn's disease, yazvennыy colitis, drepanocytemia, hypertriglyceridemia (incl. family history), acute and chronic liver disease.

Pregnancy and lactation

Use of the drug during pregnancy and lactation is contraindicated.

During the period of breastfeeding is necessary to resolve the issue or the cancellation of the drug, or termination of breastfeeding.

Cautions

Before the start of the drug necessary to carry out general medical (a detailed family and personal history, measurement of blood pressure, laboratory research) and gynecological examination (incl. breast examination, pelvic, cytological analysis of cervical smears). A similar survey in the period of the drug is carried out on a regular basis, every 6 Months.

The drug is a reliable contraceptive: Pearl Index (It measures the number of pregnancies, occurring during the use of contraceptive methods in 100 for women 1 year) when properly used is about 0.05.

In each case, before prescribing hormonal contraceptives alone are estimated benefits and possible negative effects of their reception. This issue should be discussed with the patient, that 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 any of the following conditions / diseases, you need to stop taking the drug and go to another, non-hormonal methods of contraception:

- Diseases of hemostasis;

- Conditions / diseases, predisposing to the development of cardiovascular, renal failure;

- Epilepsy;

- Migraine;

- The risk of estrogen-dependent tumors or estrogen-dependent gynecological diseases;

- Diabetes, not complicated by vascular disorders;

- Severe depression (if depression is associated with impaired metabolism of tryptophan, the purpose of correction can be applied vitamin B₆);

- Sickle cell anemia, tk. in some cases (eg, infection, gipoksiya) estrogensoderzhaschie drugs in this pathology can provoke thromboembolic events;

- Occurrence of abnormalities in laboratory tests evaluating liver function.

Thromboembolic disease

Epidemiological studies have shown, that there is a link between the use of oral hormonal contraceptives and an increased risk of arterial and venous thromboembolic disease (incl. myocardial infarction, stroke, deep vein thrombosis of the lower limbs, pulmonary embolism). We prove an increased risk of venous thromboembolic disease, but it is considerably less, than during pregnancy (60 accidents 100 thousand pregnancies).

Some researchers suggest, the probability of occurrence of venous thromboembolic disease is greater when using drugs, containing desogestrel and gestodene (third-generation drugs), than with preparations, containing levonorgestrel (the second generation drugs).

The frequency of spontaneous appearance of new cases of venous thromboembolic disease in healthy non-pregnant women, not taking oral contraceptives, is about 5 accidents 100 thousands of women a year. In the application of second-generation – 15 accidents 100 thousands of women a year, and when using the third generation drugs – 25 accidents 100 thousands of women a year.

When using oral contraceptive agents is very rare, arterial or venous thromboembolism liver, mesenteric, renal vessels or vessels of the retina.

The risk of arterial or venous thromboembolic disease increases:

- With age;

- When smoked (heavy smoking and age over 35 years refer to the risk factors);

- If there is a family history of thromboembolic disease (eg, parents, brother or sister). If you suspect a genetic predisposition, is necessary before using the product to consult with a specialist;

- Obesity (body mass index 30 kg / m²);

- When dyslipoproteinemia;

- In hypertension;

- In diseases of the heart valves, complicated with hemodynamic compromise;

- Atrial fibrillation;

- For patients with diabetes, complicated vascular lesions;

- During prolonged immobilization, after the big surgery, after surgery on the lower extremities, after serious injury.

In these cases, it assumed temporary cessation of the drug (not later than, than 4 weeks before surgery, A resume – not earlier, than 2 weeks after remobilization).

In women after giving birth increases the risk of venous thromboembolic disease.

It should be taken into account, that diabetes, systemic lupus erythematosus, hemolytic uremic syndrome, Crohn's disease, nespetsificheskiy yazvennыy colitis, drepanocytemia, increase the risk of venous thromboembolic disease.

It should be taken into account, that resistance to activated protein C, hyperhomocysteinemia, deficiency of protein C and S, antithrombin III deficiency, the presence of antiphospholipid antibodies, increase the risk of arterial or venous thromboembolic disease.

In assessing the benefit / risk ratio of the drug should be considered, that the targeted treatment of this condition reduces the risk of thromboembolism. The symptoms of thromboembolism are:

- Sudden pain in the chest, that radiates to the left arm;

- Sudden shortness of breath;

- Any unusually severe headache, continuing a long time, or first appears, especially when combined with the sudden total or partial loss of vision or diplopia, afaziej, dizziness, collapse, focal epilepsy, weakness or numbness in half of the body expressed, movement disorders, strong one-sided pain in the calf muscles, acute abdomen.

Neoplastic Diseases

Some studies have reported an increase in the frequency of cervical cancer in women, which for a long time took hormonal contraceptives, but research results are contradictory. In the development of cervical cancer play a significant role sexual behavior, infection with the human papilloma virus, and other factors.

Metaanaliz 54 Epidemiological studies have shown, that there is a relative increase in the danger of breast cancer among women, taking oral hormonal contraceptives, however, a higher detection rate of breast cancer could be associated with a regular medical examinations. Breast cancer is rare in women younger than 40 years, regardless of Togo, they take hormonal contraceptives or not, and increases with age. Pills can be regarded as one of the many risk factors. Nonetheless, the woman should be advised of the possible risk of breast cancer, based on the assessment of benefit-risk ratio (protection against ovarian cancer and endometrial).

There are a few reports on the development of benign or malignant liver tumors in women, taking long-term hormonal contraceptives. It should be borne in mind in the differential-diagnostic evaluation of abdominal pain, that may be associated with an increase in liver size or intraperitoneal bleeding.

Chloasma

Chloasma can develop in women, having a history of the disease during pregnancy. Those women, in which there is a risk of occurrence chloasma, it is necessary to avoid exposure to sunlight or ultraviolet radiation while taking Regulon.

Effectiveness

Efficacy may be reduced in the following cases: Missed pills, vomiting and diarrhea, the simultaneous use of other drugs, reduce the effectiveness of birth control pills.

If the patient is simultaneously taking other drugs, which may reduce the effectiveness of birth control pills, should use additional methods of contraception.

Efficacy may be reduced, If after several months of use appear irregular, spotting or breakthrough bleeding, In such cases it is advisable to continue taking pills until their closure in the following packaging. 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 excluding pregnancy.

Changes in laboratory parameters

Under the influence of oral contraceptive pills – due to the estrogen component – It may change the levels of certain laboratory parameters (functional parameters of the liver, kidney, adrenal, Thyroid, hemostasis, lipoprotein and transport proteins).

Additional Information

After acute viral hepatitis drug should be taken after normalization of liver function (no earlier than 6 Months).

When diarrhea or intestinal disorders, vomiting contraceptive effect may be reduced. Without stopping taking the drug, you must use an additional non-hormonal methods of contraception.

Women who smoke have an increased risk of cardiovascular disease with serious consequences (myocardial infarction, stroke). The risk depends on the age (especially in older women 35 years) and the number of cigarettes smoked.

It should warn the woman, that the drug does not protect against HIV infection (AIDS) and other diseases, sexually transmitted.

Effects on ability to drive vehicles and management mechanisms

Studies on the effect of the drug on the ability Regulon, necessary for driving and industrial machinery, not performed.

Overdose

Symptoms: nausea, vomiting, girls – bleeding from the vagina.

Treatment: first 2-3 h after administration of the drug in high doses is recommended to perform gastric lavage. No specific antidote, symptomatic treatment.

Drug Interactions

Drugs, inducing liver enzymes, such as hydantoin, barbiturates, prymydon, Carbamazepine, rifampicin, okskarʙazepin, topiramate, felʙamat, griseofulvin, St. John's wort preparations ordinary reduce the effectiveness of oral contraceptives and increase the risk of breakthrough bleeding. The maximum level of induction is usually achieved not earlier 2-3 weeks, but may take up to 4 weeks after discontinuation of the drug.

Ampicillin and tetracycline reduce the effectiveness Regulon (mechanism of interaction is not installed). If necessary, a joint reception, it is recommended to use an additional barrier method of contraception during treatment and during 7 days (for rifampicin – during 28 days) after drug withdrawal.

Oral contraceptives can reduce carbohydrate tolerance, increase the need for insulin or oral antidiabetic agents.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at temperature from 15 ° to 30 ° C. Shelf life – 3 year.