Mili is a birth control medication which contains a combination of 2 hormones, norgestimate and ethinyl estradiol, that are used to prevent ovulation.
Contents:
Indications for use
- Oral contraception.
Mechanism of action
Mili is a combined oral contraceptive, the action of which is determined by the central and peripheral mechanisms. By suppressing the release of gonadotropins, the drug prevents the maturation of eggs in the ovaries and ovulation. In addition, the agent increases the viscosity of cervical mucus, which complicates the penetration of sperm into the uterus, and acts on the endometrial epithelium, reducing the likelihood of implantation.
Dosage and mode of application
Each Mili pack contains 21 active pills (norgestimate and ethinyl estradiol) and 7 inert pills (placebo).
The drug is taken orally. Take the first pill on the first day of menstrual bleeding, for 28 days in a row, without breaks. Usually, menstrual-like bleeding begins a few days after the end of taking active pills. The next cycle of taking the contraceptive should be started without intervals. The first pill of the new cycle should be taken regardless of whether the bleeding has stopped or still continues.
The blister packaging has days of the week for the convenience of checking the regularity of taking the pills.
The contraceptive is most effective when taken at the same time of day, for example, in the morning.
After delivery, Mili drug should be started no earlier than 4 weeks after giving birth, provided that the woman does not breastfeed.
After an abortion or miscarriage for a period of up to 20 weeks of pregnancy, birth control pills can be started immediately. In these cases, the use of additional methods of contraception is not required.
After induced or spontaneous abortion at a gestational age of more than 20 weeks, the drug can be used on the 21st day after the abortion or on the first day of natural menstruation (whichever comes first). In these cases, during the first 7 days of the cycle, it is recommended to use additional backup contraceptives in addition to taking Mili. In exceptional cases, if there are medical indications to ensure immediate reliable contraception, the drug can be started 1 week after an abortion. Bear in mind that the risk of thromboembolic complications is increased when taken during the post-abortion period. If vomiting or diarrhea occurs, the pills may lose its effectiveness since it takes 4 hours to fully absorb the pill. In this case, it is recommended to continue taking the pills, complementing its effect with other contraceptives before the onset of menstruation.
Overdose
Serious cases of poisoning as a result of an overdose of Mili were not observed. Overdose can cause nausea, vomiting, and vaginal bleeding.
There is no specific antidote. In case of overdose, it is necessary to do a gastric lavage (within the first hour after taking the pill) and to carry out symptomatic therapy.
Side effects
- Cardiovascular system: arterial hypertension, myocardial infarction, cerebrovascular accident, deep vein thrombosis, arterial thromboembolism, pulmonary thromboembolism, edema;
- Tumors: benign and malignant tumors of the liver, cervical cancer and breast cancer;
- Hepatobiliary system: cholestatic jaundice, Budd-Chiari syndrome, intrahepatic cholestasis, cholelithiasis;
- Gastrointestinal tract: nausea, vomiting, abdominal pain, flatulence, colitis;
- Genital organs: intermenstrual bleeding, spotting, amenorrhea, changes in the menstrual cycle, increase in the size of uterine fibroids, vaginal candidiasis, increase in cervical secretion, erosion of the cervix, decreased libido, premenstrual syndrome, temporary infertility after the end of the drug;
- Breast glands: soreness and sensation of tension, galactorrhea, engorgement, increase in size, decrease in lactation when taken immediately after birth;
- Skin: erythema nodosum, skin rash, chloasma, exudative erythema, acne, seborrhea, alopecia, hirsutism, pigment spots on the face, hypertrichosis, pemphigoid (gestational herpes), melasma with a tendency to persist;
- Organs of vision: cataract, lesion of the optic nerve, change in the curvature of the cornea, discomfort when wearing contact lenses;
- CNS: headache, mood changes, irritability, depression, chorea;
- Metabolism: fluid retention, changes in body weight (decrease or increase), decreased glucose tolerance, changes in appetite;
- Kidneys: reduced kidney function, hemolytic-uremic syndrome;
- Others: dizziness, migraine.
If you have menstrual-like bleeding, continue taking Mili pills. If the bleeding does not stop, it is necessary to conduct an examination to eliminate organic causes. Similar recommendations also apply to the vaginal bleeding that may occur irregularly during several cycles of taking the contraceptive or for the first time after prolonged use of the drug. If bleeding does not occur at the end of the cycle, it is necessary to exclude pregnancy before starting a new pack of the preparation.
Contraindications
Mili pills are contraindicated for use in the following conditions/diseases:
- sickle cell anemia;
- liver failure;
- hypersensitivity to norgestimate, ethinyl estradiony or other components of the drug;
- venous thrombosis, including a history (including deep vein thrombosis, pulmonary thromboembolism);
- a migraine with aura;
- confirmed or suspected breast cancer;
- endometrial cancer or other confirmed or suspected estrogen-dependent neoplasms;
- benign or malignant liver tumors;
- arterial thrombosis, including a history (including acute cerebrovascular accident, myocardial infarction, retinal artery thrombosis) or precursors of thrombosis (including angina pectoris or transient ischemic attack);
- serious or multiple risk factors for arterial thrombosis;
- arterial hypertension (persistent increase in blood pressure above 160/100 mm Hg. Art.);
- hemolytic anemia;
- otosclerosis;
- diabetes mellitus with vascular lesions;
- hereditary dyslipoproteinemia;
- genetic predisposition to venous or arterial thrombosis, for example, antithrombin-lll deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antiphospholipid antibodies (antibodies against cardiolipin, a group of antibodies against negatively charged phospholipids),
genital bleeding of unknown etiology; - postmenopausal period;
- age up to 18 years;
- postpartum period (4 weeks);
- lactation period;
- confirmed or suspected pregnancy;
- cholestatic jaundice during pregnancy, including and in the anamnesis.
With caution:
- venous or arterial embolism in brothers, sisters or parents at a relatively young age;
- long-term immobilization or extensive surgery;
- risk factors for coronary heart disease, such as smoking, hyperlipidemia, hypertension or obesity;
- arterial hypertension (persistent levels of blood pressure 140-159 / 90-99 mm Hg. Art.);
- thrombophlebitis of the superficial veins and varicose veins;
- damage to the valvular apparatus of the heart with complications (mitral stenosis with atrial fibrillation);
- diabetes;
- severe depression or the presence of this disease in a history;
- systemic lupus erythematosus;
- Crohn’s disease;
- ulcerative colitis;
- hypertriglyceridemia, including in the family history;
- acute liver dysfunction during a previous pregnancy or prior use of sex hormones;
- violations of the menstrual cycle;
- renal dysfunction;
- diseases of the gallbladder;
- epilepsy;
- uterine fibroids;
- mastopathy;
- tuberculosis.
Interactions
Drugs that induce estrogen metabolizing enzymes (for example, estrogen-2-hydroxylase – coenzyme ZA4 cytochrome P-450), reduce the contraceptive effectiveness of hormonal contraceptives. It is also possible that the induction of these same isoenzymes can lead to a decrease in the blood concentration of the progestogenic component of Mili pills. Drugs and herbal agents that affect enzymes that are involved in the biological transformation of contraceptive steroid hormones may be clinically significant in this regard (for example, St. John’s wort, barbiturates, carbamazepine, phenytoin, sulfonamides, pyrazolone derivatives, rifampicin).
Some protease inhibitors and some antiretroviral drugs may increase (for example, indinavir) or decrease (for example, ritonavir) the concentration of norgestimate and ethinyl estradiol in the blood. Another type of interaction is a violation of the intrahepatic circulation of estrogen, resulting in accelerated excretion and reduced concentration of ethinyl estradiol. When taken together with some antibiotics (for example, ampicillin or tetracycline), there is insufficient cleavage of estrogen conjugates and fatty acids by intestinal bacteria.
Pregnancy and breastfeeding
Mili is contraindicated in pregnant women.
Epidemiological studies did not reveal an increase in the risk of birth defects in children whose mothers took oral contraceptives before pregnancy. In most modern studies, the teratogenic effects, in particular, heart abnormalities and shortening of the extremities, were not found in the offspring of women who mistakenly took oral contraceptives during pregnancy.
Combined oral contraceptives can affect lactation, i.e. reduce the amount and change the composition of breast milk. In addition, a small portion of contraceptive steroids and/or their metabolites can penetrate into breast milk. In this regard, Mili is contraindicated during breastfeeding.
What if I miss a pill?
If you missed an active pill (if the delay exceeds 12 hours), additional contraceptives (spermicidal suppositories, creams, condoms, etc.) should be used until the end of this cycle. At the same time, you must continue taking the pills.
Precautions
Laboratory tests
Oral contraceptives can cause changes in hormonal parameters and indicators of liver function:
- increase the levels of prothrombin and factors II, VII, VIII, IX, X, XII and XIII; decreases the level of antithrombin 3; increases platelet aggregation caused by norepinephrine;
- increase the concentration of thyroxin-binding globulin, which causes an increase in the concentration of total thyroid hormone;
- increase serum levels of other binding proteins;
- increase levels of globulins that bind sex hormones, resulting in an increase in the concentration of sex hormones; the levels of free or biologically active sex hormones decrease or do not change;
- increase high-density lipoprotein cholesterol (X-HDL) and total cholesterol, low-density lipoprotein cholesterol (X-LDL) can increase or decrease, while the ratio of X-LDL / X-HDL can decrease, and triglycerides remain without changes;
- decrease glucose tolerance;
- decrease serum folate concentration.
This change may be important from a clinical point of view if the woman became pregnant shortly after stopping the oral contraception.
Mili pills do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Before using an oral contraceptive, it is recommended that you have a complete history and conduct a thorough physical examination. Examinations should be periodically repeated in accordance with the standards of quality gynecological care.
Before using the drug, you need to get acquainted with the information in the leaflets for the medication.
If you have undiagnosed, persistent or recurring abnormal vaginal bleeding, it is necessary to exclude a malignant tumor. After suffering hepatitis, an oral contraceptive can be started 3 months (in severe cases 6 months) after the results of functional hepatic tests become normal.
Thromboembolic and other vascular complications
The use of oral contraceptives increases the risk of thromboembolic complications and thrombosis. Case-control studies have shown that the relative risk for women using oral contraceptives, compared with those who do not use these drugs, is 3:1 for the first episode of superficial vein thrombosis, 11:4 for deep vein thrombosis or thromboembolism pulmonary artery and 6:1.5 in women with diseases predisposing to thromboembolic complications. Studies have shown that the relative risk is slightly lower, about 3:1 for new cases, and about 4.5:1 for new cases requiring hospitalization. The risk of thromboembolic complications associated with the use of oral contraceptives bassed on norgestimate and ethinyl estradiol does not depend on the duration of administration of these drugs and disappears after they are discontinued. In women using oral contraceptives, the relative risk of postoperative thromboembolic complications is increased by 2-4 times. The relative risk of venous thrombosis in women with diseases predisposing to this complication is 2 times higher than in women without such diseases. If possible, oral contraceptives should not be taken at least 4 weeks before and within 2 weeks after a planned operation, which is associated with an increased risk of thromboembolism, as well as during prolonged immobilization and during the recovery period. In the early postpartum period, the risk of thromboembolic complications is also increased, and therefore women who decide not to breastfeed can begin to take oral contraceptives no earlier than 3 weeks after delivery. After an artificial or spontaneous abortion that took place on the 20th week of pregnancy or later, the use of Mili pills can be started either on the 21st day after the abortion or on the first day of the first spontaneous menstruation, whichever comes first.
The risk of vascular complications is low with oral contraceptives containing low doses of estrogen and progestogen, but this assumption has not yet received solid evidence.
The risk of serious cardiovascular side effects increases with age, as well as in heavy smokers. This risk is very high in smokers over 35 years old. Women who use oral contraceptives should be strongly advised to stop smoking.
Blood pressure has been reported in women taking oral contraceptives. It was not possible to identify differences in the frequency of hypertension in women who have taken oral contraceptives in the past, and in women who have never taken such drugs. Before you start taking an oral contraceptive, you must normalize blood pressure. In the case of a strong increase in blood pressure, the drug should be discontinued.
There are reports of the occurrence of retinal thrombosis associated with the use of birth control pills. Oral contraceptives should be discontinued in case of unexplained transient, partial or complete loss of vision; veil before eyes or diplopia; swelling of the nipple of the optic nerve or changes in the retinal vessels. In such situations, it is necessary to immediately implement appropriate diagnostic and therapeutic actions.
Liver neoplasm
Benign and malignant tumors of the liver (adenomas and hepatocellular carcinoma) are rare. The risk of these tumors may increase with the use of oral contraceptives and depends on the duration of their use. Rupture of benign liver adenomas can cause death due to internal bleeding.
Cancer of the genitals and mammary glands
The incidence of breast, endometrial, ovarian and cervical cancers in women using Mili tablets has been the subject of numerous epidemiological studies. There are conflicting results, but data from most studies have shown that the use of oral contraceptives is not associated with an overall increase in the risk of breast cancer. Some authors have reported an increase in the relative risk of breast cancer, especially in young women. This increased relative risk depends on the duration of use of birth control pills.
A meta-analysis of the results of 54 epidemiological studies shows that women who use combined oral contraceptives at the present time or have taken them in the previous 10 years have a slightly increased risk of detecting breast cancer. Based on these data, it is impossible to determine whether the increased risk of an earlier diagnosis of breast cancer in women who have ever used such drugs is due to the biological effects of hormonal contraceptives or a combination of these two factors. This meta-analysis also suggests that the age at which women stop taking Mili pills is an important risk factor for breast cancer: the older the age, the more often breast cancer is diagnosed. The duration of use of the drug is not so important.
Before using hormonal contraceptives, it is necessary to discuss the possibility of increasing the risk of breast cancer and to correlate this risk with the use of such drugs.
Liver neoplasm
Benign and malignant tumors of the liver (adenomas and hepatocellular carcinoma) are rare. The risk of these tumors may increase with the use of oral contraceptives and depends on the duration of their use. Rupture of benign liver adenomas can cause death due to internal bleeding.
Cancer of the genitals and mammary glands
The incidence of breast, endometrial, ovarian and cervical cancers in women using Mili tablets has been the subject of numerous epidemiological studies. There are conflicting results, but data from most studies have shown that the use of oral contraceptives is not associated with an overall increase in the risk of breast cancer. Some authors have reported an increase in the relative risk of breast cancer, especially in young women. This increased relative risk depends on the duration of use of birth control pills.
A meta-analysis of the results of 54 epidemiological studies shows that women who use combined oral contraceptives at the present time or have taken them in the previous 10 years have a slightly increased risk of detecting breast cancer. Based on these data, it is impossible to determine whether the increased risk of an earlier diagnosis of breast cancer in women who have ever used such drugs is due to the biological effects of hormonal contraceptives or a combination of these two factors. This meta-analysis also suggests that the age at which women stop taking Mili pills is an important risk factor for breast cancer: the older the age, the more often breast cancer is diagnosed. The duration of use of the drug is not so important.
Before using hormonal contraceptives, it is necessary to discuss the possibility of increasing the risk of breast cancer and to correlate this risk with the use of such drugs.
Some epidemiological studies have revealed that the medication can cause cervical cancer. The relationship of this disease with the use of combined oral contraceptives is not proven. It should be noted, however, the uncertainty of the extent to which these data may be due to differences in sexual behavior and other factors.
Metabolic effects
The preparation can reduce glucose tolerance. This effect is directly dependent on the dose of estrogen. In addition, progestogens can enhance insulin secretion and cause insulin resistance, and this effect is different for different progestogens. However, in women without diabetes mellitus, oral contraceptives most likely do not affect fasting blood glucose. Considering the above, it is necessary to closely monitor the status of women with impaired glucose tolerance or diabetes mellitus. A small percentage of women experience persistent hypertriglyceridemia. Some women using this preparation can experience changes in serum triglyceride and lipoprotein levels.
Headaches
If you have an unusual/intensified migraine, as well as a new type of a headache, which is recurrent, persistent or strong, it is necessary to stop taking birth control pills and find out the cause of a headache.
Menstrual disorders
Women who use hormonal contraceptives, especially in the first 3 months, may experience intermenstrual bleeding, spotting and/or amenorrhea. The non-hormonal causes of such disorders should be considered and, if necessary, appropriate diagnostic procedures should be carried out to exclude a malignant tumor or pregnancy.
In some women, amenorrhea or oligomenorrhea can occur, especially if these conditions have been observed before using the contraceptive.
Chloasma
In some cases, women taking oral contraceptives (particularly women with a history of chloasma during the previous pregnancy) may experience chloasma. Women who are prone to chloasma should avoid exposure to the sun and ultraviolet radiation while using Mili tablets. Chloasma often does not disappear completely.