Active ingredients: Gestodene, Ethinylestradiol
MINULET 0.075 mg + 0.03 mg coated tablets
Indications Why is Minulet used? What is it for?
Pharmacotherapeutic category
MINULET is a combined type contraceptive for oral use. Each tablet contains two different female hormones: gestodene and ethinyl estradiol. As all tablets in the pack contain the combination of the same hormones in the same dose, the product is considered a monophasic combined-type oral contraceptive.
Therapeutic indications
Prevention of conception.
The decision to prescribe MINULET must take into account the individual woman's current risk factors, particularly those related to venous thromboembolism (VTE) and the comparison between the risk of VTE associated with MINULET and that associated with other combined hormonal contraceptives (COCs). (see sections "Contraindications", "Precautions for use" and "Special warnings").
Contraindications When Minulet should not be used
Combined hormonal contraceptives (COCs) should not be used in the following conditions.
If these are present, it is important to inform your doctor.
Presence or risk of venous thromboembolism (VTE)
- Venous thromboembolism - current (with anticoagulant) or previous VTE (eg deep vein thrombosis [DVT] or pulmonary embolism [PE])
- Known hereditary or acquired predisposition to venous thromboembolism, such as resistance to activated protein C (including factor V Leiden), antithrombin III deficiency, protein C deficiency, protein S deficiency
- Major surgery with prolonged immobilization (see "Precautions for use" and "Special warnings" sections)
- High risk of venous thromboembolism due to the presence of multiple risk factors (see sections "Precautions for use" and "Special warnings")
Presence or risk of arterial thromboembolism (ATE)
- Arterial thromboembolism - current or previous arterial thromboembolism (e.g. myocardial infarction) or prodromal conditions (e.g. angina pectoris) o Cerebrovascular disease - current or previous stroke or prodromal conditions (e.g. transient ischemic attack, TIA))
- Known hereditary or acquired predisposition to arterial thromboembolism, such as hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant)
- History of migraine with focal neurological symptoms
- High risk of arterial thromboembolism due to the presence of multiple risk factors (see sections "Precautions for use" and "Special warnings") or the presence of a serious risk factor such as:
- • diabetes mellitus with vascular symptoms
- severe hypertension
- severe dyslipoproteinemia
- Jaundice (yellowing of the skin) or severe liver disease, present or past.
- Previous or current pancreatitis if associated with severe hypertriglyceridaemia • Tumor of the breast or genital organs (carcinoma of the endometrium), present or previous.
- Benign or malignant liver tumor, present or previous.
- Vaginal bleeding of unknown origin.
- Known or suspected pregnancy.
- Hypertension, history of hypertension, hypertension related diseases or kidney disease.
- Combination with Ritonavir.
- Hypersensitivity to the active substances or to any of the excipients.
If any of these conditions appear for the first time while using the product, stop taking it immediately and consult your doctor. In the meantime, use non-hormonal methods of contraception. See also "General Notes".
Precautions for use What you need to know before taking Minulet
General notes
This leaflet describes some situations in which it is necessary to stop taking the product or in which a reduction in the efficacy of the product itself may occur. In such situations you should not have sexual intercourse or you should take extra non-hormonal contraceptive precautions such as the use of condoms or other barrier methods. Do not use rhythm and basal temperature methods, which can be unreliable, as the pill alters the normal changes in temperature and cervical mucus that occur during the menstrual cycle.
Before starting or resuming taking the pill it is advisable to make a thorough medical examination.
Furthermore, it is advisable to carry out periodic control visits, at least once a year, during the use of the product.
The frequency and type of visit will be established by the doctor and aimed in particular at blood pressure control, breast, abdomen and general gynecological examination including a Pap test and relative blood tests.
The first follow-up visit should take place 3 months after starting the COC. The investigations required at the initial visit, described above, should be carried out at each annual visit.
Like all contraceptive pills, MINULET does not protect against HIV infection (AIDS) or any other sexually transmitted disease.
MINULET is prescribed for personal use and must not be available to several people at the same time.
Precautions
In the presence of any of the conditions listed below, the use of the combined pill may require close medical supervision. It is therefore necessary to warn your doctor of any of the above conditions before starting to use MINULET. Your doctor may recommend a completely different (non-hormonal) method of contraception.
- smoke;
- diabetes;
- overweight;
- hypertension (see "Special warnings");
- heart valve defects or certain heart rhythm disturbances;
- superficial phlebitis (venous inflammation);
- varicose veins;
- migraine (see "Special warnings");
- depression (see "Special warnings");
- epilepsy;
- current or previous high levels of cholesterol and triglycerides (fats) in the blood, even in close family members (see "Special warnings");
- breast lumps;
- history of breast cancer in close relatives;
- liver or gallbladder disease (see "Special warnings");
- Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease);
- systemic lupus erythematosus (disease affecting the skin of the whole body);
- hemolytic-uremic syndrome (blood clotting disorder causing kidney failure);
- sickle cell anemia;
- porphyria;
- present or previous chloasma (yellowish-brown pigmented patches on the skin, particularly on the face). In this case, avoid prolonged exposure to the sun or ultraviolet rays;
- previous herpes gestationis;
- some pathological conditions characterized by resistance to Activated Protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome (anticardiolipin antibodies, lupus anticoagulant), which predispose to the onset of venous or arterial thrombosis ;
- Sydenham's chorea (central nervous system disorder);
- hearing loss from otosclerosis.
In case of first appearance, recurrence or worsening of any of the above conditions while using the pill, consult your doctor.
Hypericum perforatum preparations should not be taken concomitantly with medicinal products containing oral contraceptives, digoxin, theophylline, carbamazepine, phenobarbital, phenytoin due to the risk of decreased plasma levels and decreased therapeutic efficacy of oral contraceptives, digoxin, theophylline, carbamazepine, phenobarbital, phenytoin (see section "Interactions").
Interactions Which drugs or foods may change the effect of Minulet
Inform your doctor or pharmacist that you have recently taken any other medicines, even those without a prescription.
Some drugs can prevent the pill from working effectively. These include primidone, phenytoin, barbiturates, carbamazepine (used to treat epilepsy), rifampicin (used to treat tuberculosis), ampicillin , tetracyclines, griseofulvin (antibiotics used to treat infectious diseases), ritonavir, modafinil, flunarizine, some protease inhibitors and nevirapine.
Other antiepileptic drugs (oxycarbamazepine, topiramate, felbamate) are also likely to reduce the effectiveness of the pill.
Hypericum perforatum preparations should not be administered simultaneously with oral contraceptives, as there may be a loss of contraceptive efficacy. Unwanted pregnancies and resumption of the menstrual cycle have been reported. This is due to the induction of enzymes responsible for the metabolism of drugs from Hypericum perforatum-based preparations. The induction effect may persist for at least 2 weeks after stopping treatment.
Always inform the doctor prescribing the pill about the medications you are already taking, and also inform any other doctors or dentists prescribing other medications that you are using MINULET, so that they can determine if and for how long it is needed. use additional contraceptive methods.
Substances which may increase the serum concentrations of the medicinal product:
- atorvastatin
- competitive inhibitors of sulfation in the gastrointestinal wall, such as ascorbic acid (vitamin C) and paracetamol (acetaminophen)
- substances that inhibit cytochrome P450 3A4 isoenzymes such as indinavir, fluconazole, voriconazole and troleandomycin.
Troleandomycin may increase the risk of intrahepatic cholestasis when administered concomitantly with COCs.
Ethinylestradiol can interfere with the metabolism of other drugs by inhibiting hepatic microsomal enzymes or by inducing hepatic drug conjugation, particularly glucurono-conjugation, or by other mechanisms.
Consequently, plasma and tissue concentrations may be increased (e.g. cyclosporine, theophylline, corticosteroids) or decreased (e.g. lamotrigine, levothyroxine, valproate).
Using the pill can affect the results of some blood tests, but these changes are usually within the normal range. Therefore, it is advisable to inform the doctor who requested the tests that you are taking the pill.
Warnings It is important to know that:
The medicine contains lactose and sucrose and therefore in case of ascertained intolerance to sugars contact your doctor before taking the medicine.
If any of the conditions or risk factors mentioned below are present, the suitability of MINULET should be discussed with the woman.
In the event of worsening or first appearance of any of these risk factors or conditions, the woman should consult her physician to determine whether the use of MINULET should be discontinued.
Heart attack
An increased risk of myocardial infarction has been associated with the use of COCs. The risk is primarily present in smokers or in women with other risk factors for coronary heart disease such as hypertension, hypercholesterolemia, morbid obesity, diabetes. The risk is very low. under 30 years of age.
Risk of venous thromboembolism (VTE)
The use of any combined hormonal contraceptive (COC) results in an increased risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone are associated with a lower risk of VTE. The risk associated with others. products such as MINULET can also be twofold. The decision to use a product other than those associated with a lower risk of VTE should only be made after discussions with the woman to ensure that she understands the risk of VTE associated with MINULET, the way where your current risk factors influence that risk and the fact that the risk of developing a VTE is highest in the first year of use. There is also some evidence that the risk increases when taking a COC is resumed after a break of 4 or more weeks.
About 2 in 10,000 women who do not use a CHC and who are not pregnant will develop a VTE over a period of one year. In a single woman, however, the risk can be much higher, depending on her underlying risk factors (see below).
It is estimated1 that out of 10,000 women who use a CHC containing gestodene, between 9 and 12 will develop a VTE in one year; this compares with approximately 62 women using a levonorgestrel-containing CHC.
In both cases, the number of VTEs per year is less than the number expected in pregnancy or in the postpartum period.
VTE can be fatal in 1-2% of cases.
Epidemiological studies have shown that the incidence of venous thromboembolism in users of low estrogen COCs (COCs)
In several epidemiological studies it has been observed that women using combined oral contraceptives containing ethinylestradiol, mostly at a dose of 30 µg, and a progestin such as gestodene have an increased risk of thrombotic events and venous thromboembolism compared to women using oral contraceptives. combined type containing less than 50 µg of ethinyl estradiol and the progestin levonorgestrel.
However, data from other studies did not show this increased risk.
For products containing 30 µg ethinyl estradiol in combination with desogestrel or gestodene compared to those containing less than 50 µg ethinyl estradiol and levonorgestrel, an overall relative risk of venous thromboembolic events was estimated to range from 1.5 to 2.0. The incidence of thrombotic events and venous thromboembolism for combined oral contraceptives containing levonorgestrel and less than 50 µg of ethinyl estradiol is about 20 cases per 100,000 years of use. For MINULET the incidence is about 30-40 cases per 100,000 years. woman of use, i.e. 10-20 additional cases per 100,000 woman-years of use. This figure compares with 5 to 10 cases per 100,000 woman-years for non-users.
The impact of relative risk on the number of additional cases would be greatest during the first year that a woman first uses a combined oral contraceptive. During the first year of taking the risk of thrombotic events and venous thromboembolism is greatest for all combined oral contraceptives.
All this information must be taken into consideration when prescribing this COC. When considering the choice of contraceptive method (s), all of the above information should be taken into account.
Thrombosis is the formation of a blood clot that can block a venous or arterial blood vessel.
It sometimes affects the deep veins in the legs (deep vein thrombosis). If the clot detaches from the vein in which it formed, it can reach and clog the arteries of the lungs, causing the so-called "pulmonary embolism". Deep vein thrombosis is a rare occurrence and can occur regardless of whether you take the pill or not; it can also occur during pregnancy. The risk is higher in women who use the Pill than in those who do not, but lower than in pregnant women.
In very rare cases, clots can also form in the blood vessels of the heart (where they cause heart attack) or the brain (where they cause stroke). Very rarely, thrombosis has been reported in CHC users in other blood vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries. In some cases, thrombosis can cause severe permanent disability or even be fatal.
The risk of having a heart attack or stroke increases with age and the number of cigarettes smoked. Women who take the Pill, especially those over the age of 35, must stop smoking.
If blood pressure increases while using the pill, it may be necessary to discontinue use of the product.
If you notice possible signs of thrombosis, stop taking the pill and see your doctor immediately (see also "When you need to see your doctor").
Risk factors for VTE
The risk of venous thromboembolic complications in CHC users may increase substantially if additional risk factors are present, especially if there are more than one risk factors (see table).
MINULET is contraindicated if a woman has several risk factors that increase her risk of venous thrombosis (see section "Contraindications"). If a woman has more than one risk factor, it is possible that the increased risk is greater than the sum of the individual factors; in this case her total risk of VTE should be considered. If the benefit-risk ratio is considered to be negative, a COC should not be prescribed (see section "Contraindications").
Table: Risk factors for VTE
There is no agreement on the possible role of varicose veins and superficial thrombophlebitis in the onset and progression of venous thrombosis.
The increased risk of thromboembolism in pregnancy, particularly in the 6-week period of the puerperium, must be considered (for information on "Pregnancy and lactation" see section "Pregnancy and lactation").
Symptoms of VTE (deep vein thrombosis and pulmonary embolism)
If symptoms of this type occur, women should seek immediate medical attention and inform them that they are taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include:
- unilateral swelling of the leg and / or foot or along a vein in the leg;
- pain or tenderness in the leg that may only be felt when standing or walking;
- increased sensation of heat in the affected leg; skin on the leg that is red or discolored.
Symptoms of pulmonary embolism (PE) can include:
- sudden and unexplained onset of shortness of breath and rapid breathing;
- sudden cough which may be associated with hemoptysis;
- sharp pain in the chest;
- severe light headedness or dizziness;
- rapid or irregular heartbeat.
Some of these symptoms (such as "shortness of breath" and "cough") are non-specific and may be misinterpreted as more common or less serious events (eg respiratory tract infections).
Other signs of vascular occlusion may include: sudden pain, swelling or a pale blue discoloration of one "extremity.
If the occlusion takes place in the eye, symptoms can range from painless blurring of vision to loss of vision. Sometimes vision loss occurs almost immediately.
Risk of arterial thromboembolism (ATE)
Epidemiological studies have associated the use of CHCs with an increased risk of arterial thromboembolism (myocardial infarction) or of cerebrovascular accidents (eg transient ischemic attack, stroke). Arterial thromboembolic events can be fatal.
Risk factors of ATE
The risk of arterial thromboembolic complications or a cerebrovascular accident in CHC users increases in the presence of risk factors (see table). MINULET is contraindicated if a woman has one serious risk factor or multiple risk factors for ATE that increase her risk of arterial thrombosis (see section "Contraindications"). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors; in this case her total risk should be considered. If the benefit-risk balance is believed to be negative, a COC should not be prescribed (see section "Contraindications").
Table: Risk factors of ATE
Symptoms of ATE
If symptoms of this type occur, women should contact a healthcare professional immediately and inform them that they are taking a CHC.
Symptoms of cerebrovascular accident can include:
- sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
- sudden difficulty walking, dizziness, loss of balance or coordination;
- sudden confusion, difficulty speaking or understanding;
- sudden difficulty seeing in one or both eyes;
- sudden, severe or prolonged migraine with no known cause;
- loss of consciousness or fainting with or without seizures.
Temporary symptoms suggest it is a transient ischemic attack (TIA).
Symptoms of myocardial infarction (MI) can include:
- pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm or below the breastbone;
- discomfort radiating to the back, jaw, throat, arms, stomach;
- feeling of fullness, indigestion or choking;
- sweating, nausea, vomiting or dizziness;
- extreme weakness, anxiety, or shortness of breath;
- rapid or irregular heartbeats.
Medical examinations / visits
Before initiating or resuming use of MINULET, a complete medical history (including family history) should be taken and pregnancy should be ruled out. Blood pressure should be measured and a clinical examination, guided by contraindications, should be performed (see section " Contraindications ") and warnings (see sections" Precautions for use "and" Special warnings "). It is important to draw a woman's attention to information relating to venous or arterial thrombosis, including the risk associated with MINULET compared to other CHCs, symptoms of VTE and ATE, known risk factors and what to do in the event of a suspected thrombosis.
The woman should also be advised of the need to read the package leaflet carefully and to follow its advice. The frequency and type of examinations should be based on established guidelines and should be adapted to the individual woman.
Women should be advised that hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.
Tumors
Breast cancer diagnoses are slightly more common in women who use the pill than in those of the same age who do not.The slight increase in the number of breast cancer diagnoses gradually disappears over the 10 years following discontinuation of treatment. Risk factors involved in the development of breast cancer include increasing age, family history, obesity, nulliparity and older age for the first full term pregnancy.
Benign liver tumors and even more rarely malignant liver tumors have been reported in women taking the Pill. Such tumors can cause internal bleeding. Consult your doctor immediately in case of severe pain in the abdomen.
The most important risk factor for cervical cancer is persistent human papillomavirus infection.
Cancer of the neck of the uterus (cervix) has been reported to be more common in women who use the pill for a long time. genesis of tumors in general.
Liver function
Acute or chronic disturbances of liver function may require discontinuation of COC treatment until liver function parameters have returned to normal. Return of cholestatic jaundice already occurring in pregnancy or during previous sex steroid treatment requires treatment. discontinuation of the combined oral contraceptive.
Women with a history of COC-related cholestasis or who develop cholestasis during pregnancy are more likely to experience this condition when using COCs.
These patients should be closely monitored and, if the condition recurs, the COC should be discontinued.
Acute or chronic disturbances of liver function may require discontinuation of the COC until liver function has returned to normal.
Hepatocellular injury has been reported with the use of COCs. Early diagnosis of drug-related hepatocellular injury may decrease the severity of hepatotoxicity when the drug is discontinued. If liver function impairment is diagnosed, patients should stop taking the COC, use a non-hormonal method of birth control and consult their physician.
Eye injuries
Cases of retinal thrombosis have been reported during the use of COCs. If there is unexplained partial or complete loss of vision, the onset of proptosis or diplopia, papillary edema or vascular lesions of the retina, the use of COC should be discontinued and cause should be investigated immediately.
Migraine / Headache
The appearance or exacerbation of migraine or the development of headache with the characteristic being recurrent, persistent and severe, constitute situations which require discontinuation of the combined oral contraceptive and evaluation of the cause.
Women with migraine (particularly migraine with aura) who take COCs may be at increased risk of stroke (see "Contraindications").
Angioedema
Exogenous estrogens can induce or exacerbate the symptoms of angioedema, particularly in women with hereditary angioedema.
Effects on the metabolism of lipids and carbohydrates
Glucose intolerance has been reported in patients using COCs. Although COCs may affect peripheral insulin resistance and glucose tolerance, there is no evidence for the need for regimen adjustment in diabetic patients. who use combined oral contraceptives. However, patients with diabetes or with a glucose intolerance should be carefully followed while taking the COC (see "Precautions for use").
While taking a COC, some women may experience changes in lipid values. A non-hormonal method of contraception should be considered in women with uncontrolled dyslipidaemia. Persistent hypertriglyceridaemia may occur in a small proportion of women who use a combined oral contraceptive. Increased plasma triglycerides in COC users can lead to pancreatitis and other complications.
Estrogen increases high-density plasma lipoprotein (HDL cholesterol), while a decrease in HDL cholesterol has been reported with many progestogens.
Some progestogens can elevate low-density lipoprotein (LDL) concentrations and can make controlling hyperlipidemia more difficult.
The resulting effect of a combined oral contraceptive depends on the balance achieved between the effects of the individual doses of estrogen and progestogen as well as the nature and total quantity of progestogens used in the contraceptive. The content of both hormones must be taken into account when selecting of the combined oral contraceptive.
Women who are being treated for hyperlipidaemia should be closely monitored if they choose to use COCs.
Folate levels
Serum folate levels may be decreased by combined oral contraceptive therapy. This may be of clinical importance if the woman becomes pregnant shortly after stopping the COC.
Blood pressure
The use of oral contraceptives is contraindicated in women with high blood pressure, or with hypertension-related or kidney disease or with a history of high blood pressure. Although a small rise in blood pressure has been reported in many women taking COCs, a clinically relevant increase in blood pressure rarely occurs. A relationship between COC use and hypertension has not been established, however, if clinically significant hypertension occurs during the use of a COC, the physician should, as a precaution, stop taking the COC and treat the patient. "hypertension.
Disorders of the emotional sphere
Women who, while taking COCs, present with mental depression should stop treatment and use an alternative method of contraception to determine if this symptom is drug-related. Women with a history of depression and taking oral contraceptives should be kept on closely monitored and treatment should be discontinued if severe depression occurs.
Irregular bleeding
Irregular bleeding (spotting or intermenstrual bleeding) may occur while taking any COC, especially in the first months of treatment. Therefore, the assessment of any irregular vaginal bleeding is only meaningful after a settling phase of approximately 3 cycles. of treatment.
If irregular bleeding persists or occurs after previously regular cycles, a non-hormonal etiology should be considered and appropriate diagnostic measures, including curettage, should be implemented to rule out malignant disease or pregnancy.
In some women, withdrawal bleeding may not occur during the tablet-free interval. If the COC has been taken as described in the section "Dose, method and time of administration" it is unlikely that you are pregnant. However, pregnancy is unlikely. If the COC has not been taken correctly before the missed withdrawal bleed or if two withdrawal bleeds have not occurred, pregnancy must be ruled out before continuing to take the COC. Some women may experience, after discontinuation of the oral contraceptive, amenorrhea (with a possible lack of ovulation) or oligomenorrhea, especially if this condition was pre-existing.
Laboratory tests
The use of contraceptive steroids can affect the results of some laboratory tests including liver function tests (including a decrease in bilirubin and alkaline phosphatase), thyroid (increase in total T3 and T4 due to an increase in TBG , decreased resin absorption of free T3), adrenal (increased plasma cortisol, increased cortisol-binding globulin, decreased dehydroepiandrosterone sulfate) and renal (increased plasma creatinine and decreased creatinine clearance), plasma levels transport proteins, for example corticosteroid-binding globulin and lipid / lipoprotein fractions, glucose metabolism, coagulation and fibrinolysis, decrease in serum folate levels. Changes are generally within the range of normal laboratory values.
Pregnancy and breastfeeding
MINULET should not be used in known or suspected pregnancy. If pregnancy occurs while using the COC, treatment should be stopped. There is no conclusive evidence that the estrogens and progestogens contained in the COC can harm the fetus if conception occurs accidentally while using the COC. combined (see "Contraindications").
The increased risk of thromboembolism in the postpartum period should be taken into account when "MINULET is restarted" (see sections "Dose, method and time of administration", "Precautions for use" and "Special warnings") .
MINULET is not recommended while breastfeeding.
Pediatric use
The safety and efficacy of COCs has been established in women of reproductive age. Use of these drugs before menarche is not indicated.
Geriatric use
COCs are not indicated in postmenopausal women.
Effects on ability to drive and use machines
MINULET has not been studied for its effects on the ability to drive or use machines.
WHEN YOU NEED TO CONSULT YOUR DOCTOR
Periodic checks
While using the pill, the doctor will ask the patient to undergo periodic check-ups, usually every year.
See your doctor as soon as possible:
- if you observe any change in your state of health, particularly related to what is reported in this leaflet (see also "Contraindications" and "Precautions for" use ". Do not forget the references to close family members);
- if you feel a lump in your breast;
- if other medications are to be used (see also "Interactions");
- if you are immobilized or have to undergo surgery (consult your doctor at least four weeks before);
- if you have severe and unusual vaginal bleeding;
- if you have missed tablets in the first week of use and have had sexual intercourse in the seven days preceding the forgetting;
- if you do not have a period for two consecutive cycles or if you suspect a pregnancy, do not start a new pack without your doctor's permission.
Stop taking the tablets and consult your doctor immediately if you notice possible signs of thrombosis:
- cough that starts suddenly;
- severe pain in the chest that may radiate to the left arm;
- sudden shortness of breath;
- unusual, severe, prolonged headache or migraine attack;
- partial or total loss of vision or double vision;
- slurred speech or inability to speak;
- sudden changes in hearing, smell and taste;
- feeling dizzy or faint; • weakness or numbness of any part of the body;
- severe abdominal pain;
- severe pain or swelling in one leg;
The above situations and symptoms are illustrated and explained in more detail in other sections of this leaflet.
Dosage and method of use How to use Minulet: Dosage
How to take MINULET
The MINULET pack contains 21 tablets. One tablet should be taken daily for 21 consecutive days, followed by a 7-day suspension of intake. The first tablet should be taken out of the calendar pack box marked 1 (located next to the word "START"). the next tablet must be taken the next day from the next box, following the numbering and direction of the arrows.
Pierce the blister on the day of the week on which you start taking the tablets.
This same day of the week will represent the start day of each subsequent pack; in addition, it will represent the same day of the week that tablets 1, 8 and 15 will be taken. This will help to check and make sure that you are taking the tablets correctly.
The tablets should be swallowed without chewing, regularly, possibly always at the same time, preferably after the evening meal.
Subsequent cycles
After taking all 21 tablets, stop taking it for 7 days. During these 7 days you will experience bleeding, usually 2-3 days after taking the last tablet. Start the next pack of MINULET on day 8, even if the bleeding is still ongoing. This means that the second pack of MINULET will be started exactly on the same day of the week that the first pack was started, four weeks earlier.
Beginning of the first pack
No hormonal contraceptive in the previous month.
Start taking MINULET on the first day of the cycle, ie the first day of your period, taking the tablet marked with the number 1 (see section "How to take MINULET"). You can also start between the second and fifth day of the cycle , but in this case an additional contraceptive method (barrier method) must be used for the first seven days of taking the tablets in the first cycle.
Switching from another "combined type" pill.
You can start taking MINULET the day after the last pill of the previous contraceptive (ie without observing any break). If your previous contraceptive pack also contains inactive tablets, you can take MINULET the day after the last active tablet (in case if in doubt, ask your doctor). It can also be started later, but never later than the day after the pill-free interval (or the day after the last inactive tablet) of the previous contraceptive.
Changing from a progestogen-only pill (minipill).
You can stop taking the minipill on any day and start taking MINULET the next day at the same time. However, for the first seven days of taking the tablets, use an additional method of contraception (barrier method) when having intercourse.
Changing from an injection, implant or intrauterine device contraceptive.
Start using MINULET on the day the next progestogen-only preparation injection is due, or the day the progestogen-only implant or progestogen-only intrauterine device is removed. first seven days of taking MINULET use an additional method of contraception (barrier method) when having sex.
After giving birth.
The start of the pill after childbirth must be determined by the doctor. He will decide whether to start the treatment in the period between the 21st and the 28th day, or later. In the latter case it is advisable to use an additional barrier method in the first 7 days of taking MINULET tablets. However, if sexual intercourse has occurred in the meantime, pregnancy must be ruled out or the first menstruation must be awaited before actually starting the intake of MINULET.
If you are breastfeeding and want to take MINULET, talk to your doctor first.
After a spontaneous or induced abortion.
Follow your doctor's prescription.
Termination of employment
You can stop using MINULET at any time. If you do not want to become pregnant, consult your doctor about other methods of birth control.
If you want to stop using MINULET because you want motherhood, talk to your doctor. In this case it is generally advisable to wait until your period is regular again before attempting to conceive.
WHAT TO DO IF ...
you forget to take your tablets
- If less than 12 hours have passed since the time of usual intake, the reliability of the pill is preserved. Take the forgotten tablet as soon as you remember and continue as usual.
- If more than 12 hours have passed since the time of usual intake, or if 2 or more tablets have not been taken, the reliability of the pill may be reduced. The greater the number of consecutively forgotten tablets, the greater the risk of the contraceptive effect being reduced. The risk of pregnancy is particularly high if pills are forgotten at the beginning and at the end of the pack. Follow the instructions below (see also the diagram below).
More than one tablet forgotten in one pack
Consult your doctor.
One tablet forgotten in the first week
Take the tablet as soon as you remember (even if that means taking two tablets at the same time) and continue as usual. Use additional contraceptive methods (barrier method) for the next 7 days.
If sexual intercourse took place in the week preceding the forgetfulness, there is a possibility of pregnancy. Inform your doctor immediately.
One tablet forgotten in the second week
Take the forgotten tablet as soon as you remember (even if that means taking two tablets at the same time) and continue as usual. The reliability of the pill is preserved. No additional contraceptive precautions need to be taken.
One tablet forgotten in the third week
One of the following alternatives may be chosen, without the need for additional contraceptive precautions.
- Take the forgotten tablet as soon as you remember (even if that means taking two tablets at the same time) and continue as usual. Start the new pack as soon as the current one is finished, with no gap between the two packs. Withdrawal bleeding may not occur until the second pack is finished, but intermenstrual bleeding (spotting) may occur during the days of intake. Or
- Discontinue tablets from the current pack, observe an interval of 7 days or less (also count the day of the missed pill) and continue with a new pack. If you choose this alternative, you can always start the new pack on the same day of the week on which you usually start.
If you forget to take one or more tablets and do not have a period in the first pill-free interval, you may have become pregnant. Consult your doctor before starting the new pack.
In case of vomiting and / or diarrhea
If vomiting or diarrhea occurs within 4 hours of taking MINULET, the absorption of the active ingredient may be incomplete. It is as if the tablet has been forgotten. The use of tablets from a new pack is required, as described above. Therefore, follow the instructions indicated in case of forgotten tablets.
In case of unexpected bleeding
With all oral contraceptives, vaginal bleeding can occur in the first few months of taking it between menstruation. Normally, irregular bleeding disappears once the body gets used to the pill (usually after about 3 cycles of assumption). It is always advisable to consult your doctor, but especially if these bleeding persist, become intense or recur at intervals.
In case of missed menstruation
If all the tablets have been taken correctly, no vomiting has occurred or other medications have been taken, it is very unlikely that you are pregnant. Continue using the product as usual.
If your period does not occur twice in a row, it is possible that you are pregnant. Consult your doctor immediately. Do not start the new pack until your doctor has ruled out pregnancy.
Overdose What to do if you have taken too much Minulet
Symptoms of combined oral contraceptive overdose in adults and children include nausea, breast tightness, confusion, abdominal pain, sleepiness / fatigue, withdrawal bleeding.
There are no specific antidotes and any further treatment must be symptomatic.
In case of accidental ingestion / intake of an excessive dose of MINULET, notify your doctor immediately or go to the nearest hospital.
If you have any further questions on the use of MINULET, ask your doctor or pharmacist.
Side Effects What are the side effects of Minulet
Like all MINULET medicines, it can cause side effects, although not everybody gets them.
If you experience any side effects, especially if they are severe and persistent, or a change in your health condition that you think may be caused by the pill, consult your doctor.
There is an increased risk of venous thromboembolism (VTE) for all women using a combined oral contraceptive. For information on the differences in risk between COCs, see section Special warnings.
Serious side effects
Serious reactions associated with the use of the pill, and related symptoms, which require discontinuation of treatment are also described in the section "Precautions for use": "Thrombosis" and "Tumors":
- arterial thromboembolic accidents (in particular myocardial infarction, cerebrovascular accident, transient ischemic attack);
- venous thromboembolic accidents (phlebitis, pulmonary embolism);
- hypertension, coronary heart disease;
- hyperlipidemia (hypertriglyceridemia and / or hypercholesterolemia)
- severe mastodynia, benign mastopathy;
- intense and unusual headaches, migraines, dizziness, vision changes;
- exacerbation of epilepsy;
- hepatocellular carcinoma, cholestatic jaundice;
- chloasma;
- optic neuritis, vascular thrombosis of the retina
Description of some adverse reactions
An increased risk of:
- arterial and venous thrombotic and thromboembolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism, and this risk is discussed in more detail in the "Precautions for use" and "Special warnings" sections;
- cervical intraepithelial neoplasia and cervical cancer;
- breast cancer diagnosis.
- benign liver tumors (e.g. focal nodular hyperplasia, hepatic adenoma)
For more information, read these sections of this leaflet and consult your doctor immediately.
Other side effects
The following side effects have been reported in women using the Pill:
Most common complications:
- breast tension, enlargement, pain and discharge
- headache, migraine
- changes in sexual desire, depressed mood, irritability
- intolerance to contact lenses
- nausea, feeling unwell
- nervousness
- changes in vaginal secretions
- fluid retention / edema
- changes in body weight (increase or decrease), changes in appetite (increase or decrease)
- hypersensitivity reactions
- oligomenorrhea, amenorrhea, dysmenorrhea
- intermenstrual bleeding
- vaginitis, including candidiasis
Rare complications:
- vomiting, abdominal pain and abdominal cramps
- depression
- skin disorders (acne, alopecia, seborrhea, hypertrichosis, rash, erythema nodosum, erythema multiforme)
- hypersensitivity reactions including very rare cases of urticaria, angioedema and severe reactions with respiratory and circulatory symptoms; worsening of systemic lupus erythematosus
- worsening of varicose veins
- bloated feeling
- pancreatitis
- ischemic colitis
- biliary lithiasis
- inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- decrease in serum folate levels.
COCs can worsen pre-existing gallbladder disease and can accelerate the development of this disease in previously asymptomatic women.
Compliance with the instructions contained in this leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at "www.agenziafarmaco.gov.it/it/responsabili". By reporting side effects you can help provide more information on the safety of this medicine. "
Expiry and Retention
See the expiration date printed on the package.
CAUTION: DO NOT USE THE MEDICINAL PRODUCT AFTER THE EXPIRY DATE INDICATED ON THE PACKAGE.
The expiry date indicated refers to the product in intact packaging, correctly stored.
Special precautions for storage
Store at a temperature not exceeding 25 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children.
Composition and pharmaceutical form
Composition
Each coated tablet contains: Active ingredients: gestodene 0.075 mg; ethinylestradiol 0.03 mg.
Excipients: lactose, corn starch, povidone 25,000, sodium calcium edetate, magnesium stearate, sucrose, povidone 700,000, macrogol 6000, calcium carbonate, talc, ethylene glycol ester of montanic acid (E wax).
Pharmaceutical form and content
Coated tablets for oral use.
Carton containing 1 calendar pack of 21 coated tablets.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
MINULET 0.075 MG + 0.03 MG COATED TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each coated tablet contains:
Active ingredients: gestodene 0.075 mg; ethinylestradiol 0.03 mg.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Coated tablets for oral use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Prevention of conception.
04.2 Posology and method of administration
METHOD OF RECRUITMENT
The MINULET pack contains 21 tablets. One tablet should be taken a day for 21 consecutive days, followed by a suspension of intake for 7 days. The first tablet should be taken out of the calendar pack box marked "1" (located next to the word "START") .
The next tablet must be taken the next day from the next box, following the direction of the arrows: in this way it is easy to check, day by day, whether the tablet has been taken or not.
The tablets should be swallowed without chewing, every day, possibly at the same time, preferably after the evening meal.
After taking all 21 tablets, stop taking it for 7 days.
A withdrawal bleed usually starts 2 or 3 days after the last tablet and may not have finished before the next pack is started.
Each subsequent pack is started the day after the tablet-free break.
This means that the second pack of MINULET will be started exactly on the same day of the week that the first pack was started, four weeks earlier.
HOW TO START THE TREATMENT WITH MINULET
No hormonal contraceptive treatment in the previous month
The intake of MINULET tablets must begin on the 1st day of the natural menstrual cycle (ie the first day of menstruation). It is also possible to start MINULET between the 2nd and 5th day of the cycle but, in this case, during the first cycle, it is also recommended to use a non-hormonal barrier method of contraception (eg condom or spermicide) in the first seven days of taking MINULET tablets.
Changing from another combined oral contraceptive
The first MINULET tablet should preferably be taken the day after the last active tablet of the previous contraceptive or at the latest the day after the usual tablet-free break or the day after the last placebo tablet of the previous oral contraceptive.
Changing from a progestogen-only contraceptive (minipill, implant, intrauterine device, prepared for injection)
It is possible to change at any time if you are coming from the minipill, and the intake of MINULET must start the next day. In the case of an implant, the intake of MINULET must begin on the same day as the progestogen-only implant or the A progestogen-only intrauterine device is removed or, in the case of a progestogen-only injectable preparation, on the day the next injection should be given. In all these cases the woman should also be advised to also use a non-hormonal method of contraception. support for the first seven days of taking MINULET tablets.
After a first trimester abortion
Treatment with MINULET can be started immediately without the need for additional contraceptive measures.
After a birth or second-trimester abortion
Since the immediate postpartum period is associated with an increased risk of thromboembolism, MINULET should not be started earlier than the 21st-28th day postpartum in non-breastfeeding mothers or after a second trimester abortion. She should also be advised to use a non-hormonal method of contraception during the first seven days of taking MINULET tablets. However, if sexual intercourse has occurred in the meantime, pregnancy must be ruled out or the first menstruation should be waited for before actually starting MINULET (see sections 4.4 "Thromboembolism" and 4.6).
IRREGULAR INTAKE OF TABLETS
Contraceptive protection may decrease if you forget to take the tablets, particularly if the forgotten occurs during the first days of the treatment cycle.
If the delay in taking any tablet is less than 12 hours from the usual time, contraceptive protection is not reduced. The forgotten tablet should be taken as soon as the forgotten tablet is forgotten and subsequent tablets should be taken at the usual time.
If the delay in taking any tablet is more than 12 hours from the usual time or if 2 or more tablets have not been taken, contraceptive protection is no longer ensured. Consequently, the following suggestions can be given in daily practice.
First week
The last missed tablet should be taken as soon as the forgotten tablet is noticed, even if this means taking two tablets on the same day. Subsequent tablets should be taken at the usual time. In addition, a non-hormonal method of contraception (e.g. condoms) should be used for the next 7 days. . If sexual intercourse took place during the previous week, the possibility of pregnancy should be considered. The greater the number of missed tablets and the shorter the pill-free interval, the greater the risk of pregnancy.
Second week
The last missed tablet should be taken as soon as the forgotten tablet is noticed, even if this means taking two tablets at the same time. Subsequent tablets should be taken at the usual time. . It is not necessary to use any contraceptive method , provided that, in the 7 days preceding the first forgotten tablet, the tablets have been taken correctly; however, if not, or if more than one forgotten tablet, the use of additional precautions for 7 days should be recommended.
Third week
Given the imminence of the tablet-free interval, the risk of reduced contraceptive reliability is greater. However, modifying the pill-taking pattern can still prevent the reduction of contraceptive protection. There is therefore no need to use additional contraceptive methods when using either of the following two options, as long as all tablets have been taken correctly in the 7 days preceding the first missed tablet. Otherwise it should be recommended to follow the first of the two options and also to use additional precautions for the next 7 days.
1. The last missed tablet should be taken as soon as the forgotten tablet is noticed , even if this means taking two tablets on the same day. Subsequent tablets should be taken at the usual time. . The next pack should be started immediately after finishing the previous one, ie without observing the pill-free interval between the two packs. In this case, withdrawal bleeding is unlikely to occur before the end of the second pack; however, during the " taking the tablets, spotting or breakthrough bleeding may occur.
2.You may also be advised to stop taking tablets from the current pack. You should therefore observe a pill-free interval of up to 7 days, including those in which tablets have been missed, and then continue with a new pack. .
If tablets have been missed and there is no withdrawal bleeding in the first regular tablet-free interval, the possibility of an ongoing pregnancy should be considered.
RECOMMENDATIONS IN CASE OF VOMITING AND / OR HEADING
If vomiting or diarrhea occurs within 4 hours of taking the tablet, absorption of the tablets may be incomplete. The use of tablets from a new pack is required, as described above. Refer to the recommendations outlined in the section "IRREGULAR TABLET TAKING". from a new package.
04.3 Contraindications
Combined oral contraceptives should not be used in the following cases:
• hypersensitivity to the active substances or to any of the excipients
• arterial thromboembolic accidents or arterial thromboembolic pathology in history (in particular myocardial infarction, cerebrovascular accident)
• venous thromboembolic accidents or venous thromboembolic disease in history (deep vein thrombosis, pulmonary embolism), with or without triggers
• current or previous prodrome of a thrombosis (for example, transient ischemic attack, angina pectoris)
• cardiovascular disorders: hypertension, history of hypertension, diseases related to hypertension or kidney disease, coronary artery disease, valvulopathy, rhythm disturbances that can cause blood clots
• hereditary or acquired predisposition for venous or arterial thrombosis
• headache with focal neurological symptoms, such as aura
• diabetes complicated by micro- or macroangiopathy
• ophthalmic pathology of vascular origin
• severe liver disease, either current or past, until liver function values have returned to normal
• current or previous pancreatitis, if associated with severe hypertriglyceridaemia
• liver tumors, current or past, benign or malignant
• known or suspected malignant diseases of the genital organs (carcinoma of the endometrium) or of the breast, if hormone-dependent
• cholestatic jaundice in pregnancy or jaundice in conjunction with previous use of COCs
• vaginal bleeding of an unknown nature
• known or suspected pregnancy
• association with Ritonavir.
The presence of one or more risk factors for venous or arterial thrombosis may constitute a contraindication to use (see section 4.4). If any of these conditions appear for the first time during the use of the oral contraceptive, the intake of prepared must be stopped immediately.
04.4 Special warnings and appropriate precautions for use
MEDICAL EXAMINATION
A thorough personal and family medical history and a physical physical examination (including blood pressure determination) should be taken prior to initiating or re-administering a COC, as indicated in the "Contraindications" sections (section 4.3) and "Special Warnings"; Physical examination should be repeated at least annually during COC use. A PAP should be performed if the patient has / has had promiscuous sexual activity or as otherwise indicated. Periodic medical evaluation is also important, as some contraindications (for example a transient ischemic attack, etc.) or risk factors (for example a "family history of venous or arterial thrombosis) may appear for the first time during" use of a combined oral contraceptive. The frequency and type of these assessments should be individually tailored to the patient, but should generally pay particular attention to blood pressure, breast, liver, extremities, abdomen and pelvis, including cervical cytology (PAP test) and related laboratory tests.
The first follow-up visit should take place 3 months after the start of the COC. The investigations required at the initial visit and described above should be carried out at each annual visit.
Women should be warned that oral contraceptives do not protect against HIV infection (AIDS) or other sexually transmitted diseases.
SPECIAL WARNINGS
Cigarette smoking increases the risk of serious cardiovascular side effects associated with the use of COCs. This risk increases with age and with the number of cigarettes smoked (15 or more cigarettes per day), and is more pronounced in women. over 35 years of age. Women using COCs should be strongly advised not to smoke.
MINULET therefore contains lactose It must not be used by patients with hereditary galactose intolerance, Lapp lactase deficiency or in the case of glucose / galactose malabsorption syndrome.
MINULET contains sucrose and is not suitable for people with hereditary fructose intolerance, glucose / galactose malabsorption syndrome or sucrase-isomaltase deficiency.
THROMBOEMBOLIC DISORDERS AND OTHER CARDIOVASCULAR PROBLEMS
Heart attack
An increased risk of myocardial infarction has been associated with the use of COCs. The risk is primarily present in smokers or in women with other risk factors for coronary heart disease such as hypertension, hypercholesterolemia, morbid obesity, diabetes. The risk is very low. under 30 years of age.
Risk of arterial and venous thromboembolic disease
Before prescribing COCs, it is necessary to carry out systematic research on the presence of risk factors for arterial and venous thromboembolic disease and to consider contraindications and precautions for use.
Therapy should be discontinued if warning symptoms of impending complications occur: unusual intense headaches, visual disturbances, elevated blood pressure, clinical signs of phlebitis and pulmonary embolism.
Limiting exposure to estrogen and progestogen as much as possible is in accordance with the principles of Good Therapeutic Practice. For any estrogen-progestogen combination, the prescribed dosage regimen should be one that contains the lowest amount of effective estrogen and progestogen compatible with a low rate of failure and with the patient's individual needs Women who are using COCs for the first time should be prescribed preparations containing less than 50 mg of estrogen.
Risk of venous thromboembolism (VTE)
The use of any combined oral contraceptive carries an increased risk of venous thrombotic events and thrombo-embolic events such as deep vein thrombosis and pulmonary embolism, compared with non-use. The increased risk is greatest during the first year of use in a woman starting a COC for the first time. This increased risk is however lower than the risk of thrombotic events and venous thromboembolism associated with pregnancy which it is estimated in 60 cases per 100,000 pregnant woman years. Venous thromboembolism is fatal in 1-2% of cases.
Epidemiological studies have shown that the incidence of venous thromboembolism in users of low estrogen COCs (COCs)
Several epidemiological studies have shown that users of combined oral contraceptives containing ethinylestradiol, mostly at a dose of 30 micrograms, and a progestin such as gestodene have an increased risk of thrombotic events and venous thromboembolism compared to women using combined oral contraceptives. containing less than 50 mcg of ethinylestradiol and the progestin levonorgestrel.
However, data from some additional studies did not show this increased risk.
For products containing 30 micrograms of ethinylestradiol in combination with desogestrel or gestodene compared to those containing less than 50 micrograms of ethinylestradiol and levonorgestrel, an overall relative risk of venous thromboembolic events was estimated to be between 1.5 and 2.0. The incidence of thrombotic events and venous thromboembolism for combined oral contraceptives containing levonorgestrel and ethinylestradiol less than 50 mcg is approximately 20 cases per 100,000 woman-years. For products containing 30 mcg ethinyl estradiol in combination with desogestrel or gestodene L. incidence is about 30-40 cases per 100,000 woman-years, i.e. 10-20 additional cases per 100,000 woman-years. This figure compares with 5-10 cases per 100,000 woman-years in non-users. The impact of relative risk on the number of additional cases would be greatest during the first year that a woman first uses a combined oral contraceptive. During the first year of taking the risk of thrombotic events and venous thromboembolism is greatest for all combined oral contraceptives.
All this information must be taken into consideration when prescribing. When considering the choice of contraceptive method (s), all of the above information should be taken into account.
Extremely rarely, thrombosis of other vascular areas, e.g. hepatic, mesenteric, renal or retinal artery or vein, has been reported in women taking COCs. There is no consensus that the occurrence of these events is associated with the use of combined oral contraceptives.
Symptoms of venous or arterial thrombosis can include: pain and / or swelling in one leg; sudden severe pain in the chest, whether or not it radiates to the left arm; sudden shortness of breath; cough that starts suddenly; unusual, severe, prolonged headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; dizziness; collapse with or without focal seizure; weakness or marked numbness suddenly affecting one side or part of the body; motor disturbances; acute abdomen.
The risk of thromboembolism (venous and / or arterial) increases with:
- age;
- smoking habit;
- obesity (body mass index greater than 30 kg / m2);
- dyslipoproteinemia;
- hypertension;
- heart valve defect;
- atrial fibrillation;
- prolonged immobilization, major surgery, any leg operation or severe trauma. In these circumstances it is recommended to stop taking the combined oral contraceptive (in the case of elective surgery, which increases the risk of thrombosis) at least 4 weeks before the operation and to resume it no earlier than 2 weeks after complete recovery.
- a recent birth or second-trimester abortion: since the period immediately following delivery is associated with an increased risk of thromboembolism, COCs should be started no earlier than 28 days after delivery in a woman who is not breastfeeding, or after a second trimester abortion.
Arterial thrombosis and thromboembolism
The use of COCs increases the risk of arterial thrombotic and thromboembolic episodes.
Episodes reported include myocardial infarction and cerebrovascular events (ischemic and haemorrhagic stroke, transient ischemic attack). For information on vascular thrombosis of the retina see the section "Eye lesions".
The risk of thrombotic and thromboembolic arterial events is further increased in women with underlying risk factors.
Caution should be exercised when prescribing COCs to women with risk factors for thrombotic and thromboembolic episodes.
• There is no consensus on the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.
• The increased risk of thromboembolism during the puerperium should be considered (for information see section 4.6).
• Other medical conditions that have been associated with circulatory adverse events include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease and ulcerative colitis) and sickle cell anemia.
An increase in the frequency or severity of migraines while using a COC (which may be prodromal of a cerebrovascular event) may be a reason to immediately stop taking the COC.
Biochemical factors that may be indicative of hereditary or acquired predisposition to venous or arterial thrombosis include Activated Protein C resistance, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibody syndrome (anticardiolipin antibodies, lupus anticoagulant ).
In considering the risk / benefit ratio, physicians should bear in mind that adequate treatment of a clinical condition may reduce the associated risk of thrombosis, and that the risk associated with pregnancy is higher than that associated with the use of combined oral contraceptives. .
CANCERS
Carcinoma of the reproductive organs and breast
The most important risk factor for cervical cancer is persistent human papillomavirus infection.
An increased risk of cervical cancer (cervical intraepithelial neoplasia and invasive cervical cancer) has been reported in some epidemiological studies in women on long-term treatment with COCs; however, there is still no consensus on the extent to which this finding is attributable to confounding effects due to sexual behavior and other factors such as human papilloma virus (HPV).
Risk factors involved in the development of breast cancer include increasing age, family history, obesity, nulliparity and advanced age for the first full term pregnancy.
A meta-analysis of 54 epidemiological studies found that women who are currently using COCs have a slightly increased relative risk of breast cancer (RR = 1.24) and that the increased risk gradually disappears over the 10-year period. interruption of treatment. Since breast cancer is rare in women under the age of 40, the extra number of breast cancers diagnosed in women taking or recently taking a combined oral contraceptive is low compared to the risk of breast cancer. it runs during a woman's entire life.
In case of undiagnosed abnormal genital bleeding, adequate diagnostic measures are indicated.
Hepatic neoplasia
Benign liver tumors and, even more rarely, malignant liver tumors have been reported rarely in women taking COCs. In isolated cases, these tumors have resulted in life-threatening intra-abdominal haemorrhage. If a woman taking a combined oral contraceptive develops severe upper abdominal pain, liver enlargement, or signs suggestive of intra-abdominal haemorrhage, the possibility of liver cancer should be considered when making the diagnosis.
OTHER CONDITIONS
Cerebrovascular disease
COCs have been shown to increase the risk of cerebrovascular episodes (thrombotic and haemorrhagic stroke). The risk is higher among hypertensive women over 35 years of age and also smokers.
Hypertension has been shown to be a risk factor for both contraceptive users and non-contraceptive women for both types of stroke, while smoking appears to increase the risk of hemorrhagic stroke.
Liver function
Acute or chronic disturbances of liver function may require discontinuation of COC treatment until markers of liver function have returned to normal. Return of cholestatic jaundice already occurring in pregnancy or during previous sex steroid treatment requires treatment. discontinuation of the combined oral contraceptive.
Women with a history of COC-related cholestasis or women who develop cholestasis during pregnancy are more likely to experience this condition when using COCs. These patients taking a COC should be closely monitored and if cholestasis recurs, the combined oral contraceptive should be discontinued.
Acute and chronic disturbances of liver function may require discontinuation of the COC until liver function has returned to normal.
Eye injuries
Cases of retinal thrombosis have been reported during the use of COCs. If there is unexplained partial or complete loss of vision, the onset of proptosis or diplopia, papillary edema or vascular lesions of the retina, the use of COC should be discontinued and cause should be investigated immediately.
Migraine / Headache
The appearance or exacerbation of migraine or the development of headache with the characteristic being recurrent, persistent and severe, constitute situations which require discontinuation of the combined oral contraceptive and evaluation of the cause.
Women with migraine (particularly migraine with aura) taking COCs may be at increased risk of stroke (see section 4.3).
Angioedema
Exogenous estrogens can induce or exacerbate the symptoms of angioedema, particularly in women with hereditary angioedema.
Effects on the metabolism of lipids and carbohydrates
Glucose intolerance has been reported in patients using COCs. Although COCs may affect peripheral insulin resistance and glucose tolerance, there is no evidence for the need for regimen adjustment in diabetic patients. who use combined oral contraceptives. However, patients with diabetes or glucose intolerance should be closely monitored when taking the COC (see section 4.4 "Special warnings and precautions for use").
A small percentage of women experience changes in lipid values while taking a COC. In women with uncontrolled dyslipidaemia, a non-hormonal method of contraception should be considered. Persistent hypertriglyceridaemia may occur in a small proportion of women using a combined oral contraceptive. Increased plasma triglycerides in COC users can lead to pancreatitis and other complications.
Estrogen increases high-density plasma lipoprotein (HDL cholesterol), while a decrease in HDL cholesterol has been reported with many progestogens.
Some progestogens can elevate low-density lipoprotein (LDL) concentrations and can make controlling hyperlipidemia more difficult.
The resulting effect of a combined oral contraceptive depends on the balance obtained between the doses of estrogen and progestin as well as the nature and total amount of progestogen used in the contraceptive. The content in both hormones must be taken into account when choosing the oral contraceptive. combined.
Women who are being treated for hyperlipidaemia should be closely monitored if they choose to use COCs.
Folate levels
Serum folate levels may be decreased by combined oral contraceptive therapy. This may be of clinical importance if the woman becomes pregnant shortly after stopping the COC.
Fluid retention
COCs should be prescribed with caution to women whose medical conditions may be aggravated by fluid retention.
Blood pressure
The use of oral contraceptives is contraindicated in women with high blood pressure or with hypertension related disease or kidney disease or a history of high blood pressure (see section 4.3).
Although a small increase in blood pressure has been reported in many women taking COCs, a clinically relevant increase in blood pressure rarely occurs. A relationship between COC use and hypertension has not been established. However, if clinically significant hypertension occurs during the use of a COC, the physician should, as a precaution, stop taking the COC and treat the hypertension.
Pathologies of the intestine
Crohn's disease and ulcerative colitis have been reported in association with combined oral contraceptive use.
Disorders of the emotional sphere
Women who have significant mental depression while taking COCs should discontinue treatment and use an alternative method of contraception to determine if this symptom is drug-related. Women with a history of depression and taking oral contraceptives should be closely monitored monitoring and treatment should be stopped if severe depression occurs.
Irregular bleeding
Irregular bleeding (spotting or intermenstrual bleeding) may occur while taking any COC, especially in the first months of treatment. Therefore, the assessment of any irregular vaginal bleeding is only meaningful after a settling phase of approximately 3 cycles. of treatment.
If irregular bleeding persists or occurs after previously regular cycles, a non-hormonal etiology should be considered and appropriate diagnostic measures, including curettage, should be implemented to rule out malignant disease or pregnancy.
In some women, withdrawal bleeding may not occur during the tablet-free interval. If the COC has been taken as described in section 4.2, it is unlikely that she is pregnant. COC has not been taken correctly or if two withdrawal bleeds have not occurred, pregnancy must be ruled out before continuing to take the COC.
Chloasma may occasionally occur while taking COCs, especially in women with a history of chloasma gravidarum; patients with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation.
The onset or worsening of the conditions listed below has been reported both during pregnancy and while taking COCs; however, there is no conclusive evidence regarding the correlation between these conditions and COCs: jaundice and / or pruritus from cholestasis, gallstone formation, porphyria, systemic lupus erythematosus, uraemic-haemolytic syndrome, Sydenham's chorea, herpes gestationis, hearing loss from otosclerosis.
Pediatric use
The safety and efficacy of COCs has been established in women of reproductive age. The use of these drugs before menarche is contraindicated.
Geriatric use
COCs are not indicated in postmenopausal women.
REDUCTION OR LOSS OF EFFECTIVENESS
The efficacy of COCs may decrease in case of forgetting to take tablets (see section 4.2 "IRREGULAR TABLET TAKING"), in case of vomiting and / or diarrhea (see section 4.2 "RECOMMENDATIONS IN CASE OF VOMITING AND / OR DIARREA ") or taking other medicines at the same time (see section 4.5).
Hypericum perforatum preparations should not be taken concomitantly with medicinal products containing oral contraceptives, digoxin, theophylline, carbamazepine, phenobarbital, phenytoin due to the risk of decreased plasma levels and decreased therapeutic efficacy of oral contraceptives, digoxin, theophylline, carbamazepine, phenobarbital, phenytoin (see section 4.5 Interactions).
04.5 Interactions with other medicinal products and other forms of interaction
INTERACTIONS
Interaction with other drugs resulting in increased clearance of sex hormones may lead to intermenstrual bleeding or reduce the efficacy of the oral contraceptive.
Substances which may decrease the serum concentrations of ethinylestradiol:
Contraindicated associations
Ritonavir: risk of reduced contraceptive efficacy due to decreased plasma levels of estrogen.
Associations not recommended
Enzyme inducers: anticonvulsants (phenobarbital, phenytoin, primidone, carbamazepine), rifabutin, rifampicin, griseofulvin, dexamethasone, topiramate, phenylbutazone: risk of decreased contraceptive efficacy due to increased hepatic metabolism during treatment and for the cycle following the suspension of treatment.
Modafinil: risk of reduced contraceptive efficacy during treatment and for the cycle following discontinuation of treatment.
Some protease inhibitors and probably also oxycarbamazepine, felbamate and nevirapin.
Hypericum perforatum (St. John's wort), probably by induction of hepatic microsomal enzymes.
Associations to be evaluated
Some antibiotics (for example ampicillin, tetracycline): risk of reduction of contraceptive efficacy due to reduction of the enterohepatic circulation of estrogens.
Substances which may increase the serum concentrations of ethinylestradiol:
- atorvastatin
- competitive inhibitors of sulfation in the gastrointestinal wall, such as ascorbic acid (vitamin C) and paracetamol (acetaminophen)
- substances that inhibit cytochrome P450 3A4 isoenzymes such as indinavir, fluconazole, voriconazole and troleandomycin.
Troleandomycin may increase the risk of intrahepatic cholestasis during co-administration with COCs.
Ethinyl estradiol may interfere with the metabolism of other drugs by inhibiting hepatic microsomal enzymes or by inducing hepatic drug conjugation, particularly glucurono-conjugation or by other mechanisms.
Consequently, plasma and tissue concentrations may either be increased (e.g. cyclosporine, theophylline, corticosteroids) or decreased (e.g. lamotrigine, levothyroxine and valproate).
Women undergoing short-term treatment with one or more drugs belonging to any of the classes mentioned must temporarily adopt, in addition to the combined oral contraceptive, a barrier method, for the entire duration of concomitant intake of the drug and for the 7 days following the discontinuation of therapy. In the case of treatment with rifampicin, together with the combined oral contraceptive, a barrier method should be used throughout the time of taking rifampicin and for 28 days after discontinuing therapy. If concomitant drug administration continues after the end of a COC pack, the next COC pack should be started without observing the usual tablet-free interval.
In case of long-term treatment with hepatic enzyme inducers, it is recommended to increase the dose of contraceptive steroids. If a high dose of oral contraceptive is not indicated or seems unsatisfactory or unreliable, for example in case of irregular periods, the use of another contraceptive method should be recommended.
Flunarizine: risk of galactorrhea due to the increased sensitivity of the breast tissue to prolactin due to the action of flunarizine.
Preparations based on Hypericum perforatum must not be administered simultaneously with oral contraceptives, as this could lead to a loss of contraceptive efficacy. Unwanted pregnancies and resumption of the menstrual cycle have been reported. This is due to the induction of enzymes responsible for the metabolism of drugs from Hypericum perforatum-based preparations. The induction effect may persist for at least 2 weeks after stopping treatment with Hypericum perforatum products.
LABORATORY EXAMS
The use of contraceptive steroids can influence the results of some laboratory tests including liver function tests (reduction of bilirubin and alkaline phosphatase), thyroid (increase in total T3 and T4 due to an increase in TBG, decrease free T3 resin absorption), adrenal (increased plasma cortisol, increased cortisol-binding globulin, decreased dehydroepiandrosterone sulfate) and renal (increased plasma creatinine and creatinine clearance), plasma protein levels of transport, for example of corticosteroid-binding globulin and lipid / lipoprotein fractions, glucose metabolism, coagulation and fibrinolysis, decrease in serum folate levels. Changes are generally within the range of normal laboratory values.
04.6 Pregnancy and lactation
Pregnancy
The product is not indicated during pregnancy.
Unlike diethylstilbestrol, current clinical data and the results of numerous epidemiological studies allow us to consider the risk of malformations related to the administration of estrogen at the beginning of pregnancy, alone or in combination, to be reduced.
Furthermore, the risks related to the sexual differentiation of the fetus (in particular female), which have been described with the first highly androgenomimetic progestogens, cannot be extrapolated to the more recent progestogens (such as that used in this medicinal product), which are markedly less, or not at all, androgenomimetics.
Consequently, the discovery of a pregnancy in a patient taking an "estrogen-progestogen combination" does not justify the abortion.
If pregnancy occurs while using the COC, treatment should be stopped. There is no conclusive evidence that the estrogens and progestogens contained in the COC can harm the fetus if conception occurs accidentally while using the COC. combined (see section 4.3 "Contraindications").
Feeding time
Breastfeeding can be influenced by COCs, as they can reduce the quantity and change the composition of breast milk. The use of COCs should therefore be discouraged until the end of breastfeeding. Small amounts of steroids. contraceptives and / or their metabolites may be excreted in milk but there is no evidence that this affects the health of the baby.
04.7 Effects on ability to drive and use machines
MINULET has not been studied for its effects on the ability to drive or use machines.
04.8 Undesirable effects
There is an increased risk of venous thromboembolism (VTE) for all women using a combined oral contraceptive. For information on the differences in thrombotic risk between COCs, see section 4.4.
The following side effects have been reported in women using COCs:
Relatively rare complications which, however, require discontinuation of treatment:
- arterial thromboembolic accidents (in particular myocardial infarction, cerebrovascular accident, transient ischemic attack);
- venous thromboembolic accidents (phlebitis, pulmonary embolism);
- hypertension, coronary heart disease;
- hyperlipidemia (hypertriglyceridemia and / or hypercholesterolemia)
- severe mastodynia, benign mastopathy;
- intense and unusual headaches, migraines, dizziness, changes in vision;
- exacerbation of epilepsy;
- hepatocellular carcinoma, cholestatic jaundice;
- chloasma;
- optic neuritis, vascular thrombosis of the retina.
More common complications that do not generally require discontinuation of treatment, but for which the use of an alternative oral contraceptive combination may be considered:
- nausea, light headaches, weight changes (increase or decrease), irritability, nervousness, heaviness in the legs;
- breast tenderness, tenderness to touch, increase in volume, discharge;
- intermenstrual bleeding, changes in vaginal discharge, oligomenorrhea, amenorrhea, dysmenorrhea, changes in libido;
- eye irritation with the use of contact lenses.
Rarely:
- skin disorders (alopecia, acne, seborrhea, hypertrichosis, rash, erythema nodosum, erythema multiforme)
- depressed mood
- vomiting and abdominal cramps
- hypersensitivity reactions including very rare cases of urticaria, angioedema and severe reactions with respiratory and circulatory symptoms. Worsening of systemic lupus erythematosus.
- worsening of varicose veins.
- feeling of bloating.
- glucose intolerance and worsening of porphyria
- pancreatitis
- ischemic colitis
- biliary lithiasis
- inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- decrease in serum folate levels.
Other side effects that may occur commonly:
- fluid retention / edema, changes in appetite (increase or decrease), vaginitis, candidiasis
The use of COCs has been associated with an increased risk of:
- arterial and venous thrombotic events and thromboembolic events, including myocardial infarction, stroke, transient ischemic attack, venous thrombosis and pulmonary embolism
- cervical intraepithelial neoplasia and cervical cancer
- diagnosis of breast cancer.
- benign liver tumors (e.g. focal nodular hyperplasia, hepatic adenoma).
COCs can worsen pre-existing gallbladder disease and can accelerate the development of this disease in previously asymptomatic women.
Effects on discontinuation of treatment: post-treatment amenorrhea.
When treatment is stopped, amenorrhea with no ovulation may be observed (which occurs more frequently in women with previous cycle irregularities). This usually resolves spontaneously. If it continues, investigations into the possibility of pituitary disorders are advisable before any further prescription.
04.9 Overdose
Symptoms of COC overdose in adults and children include nausea, breast tenderness, confusion, abdominal pain, sleepiness / fatigue, withdrawal bleeding.
There are no specific antidotes and any further treatment must be symptomatic.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: systemic hormonal contraceptives; fixed estrogen-progestogen associations.
ATC code: G03AA10
COCs work by suppressing gonadotropins.Although the primary mechanism of this action is the inhibition of ovulation, other alterations include the change in cervical mucus (which increases the difficulty of the sperm entering the uterus) and the change in the endometrium (which reduces the likelihood of " plant).
When COCs are taken consistently and correctly, the probable failure rate is 0.1%; however in common practice, the failure rate for all oral contraceptives is 5%. The effectiveness of most contraceptive methods depends on their correct use. Failure of the method is more likely if the combined oral contraceptive tablets are forgotten.
The following non-contraceptive benefits related to the use of COCs are supported by epidemiological studies that have widely used formulations containing doses greater than 35 mcg of ethinylestradiol or 50 mcg of mestranol.
EFFECTS ON THE MENSTRUAL CYCLE
Improvement of the regularity of the menstrual cycle.
Reduction of blood loss and reduction of the incidence of iron deficiency anemia.
Decrease in the incidence of dysmenorrhea.
EFFECTS RELATED TO THE "INHIBITION OF" OVULATION
Decrease in the incidence of functional ovarian cysts.
Decrease in the incidence of ectopic pregnancies.
OTHER EFFECTS
Decreased incidence of fibroadenomas and fibrocystic breast disease.
Decrease in the incidence of acute pelvic inflammatory disease.
Decrease in the incidence of endometrial cancer.
Decrease in the incidence of ovarian cancer.
Reduced severity of acne.
05.2 Pharmacokinetic properties
Gestodene is completely and rapidly absorbed in the digestive tract. The maximum blood levels are reached after about an hour. It is not subjected to a strong "first pass effect"; it has a half-life in the terminal phase rather short and lower than that of levonorgestrel. The elimination occurs mainly via renal with a half-life of approximately 24 hours. Within 7 days after a single administration, urinary or faecal elimination is practically complete.
"Ethinylestradiol is rapidly and completely absorbed in the digestive tract; the blood peak is reached after about 1 hour. Blood levels decrease relatively quickly in a first phase and more slowly in a second phase (half-life 26 hours). L" 40% elimination occurs in the urine and 60% in the faeces.
05.3 Preclinical safety data
Toxicity
The acute toxicity of the two components is low:
Similarly, the toxicity of the combination of the two steroids is low. In the ratios 1: 0.60, 1: 0.57 and 1: 0.30 the acute toxicity was always> 4 g / kg in mice and rats, for os.
Chronic toxicity investigations of the association of the two active ingredients, conducted in rats (26-27 weeks) and dogs (27-28 weeks) did not show any organotoxic effect even at higher doses. The only alterations observed (atrophy of testicles and prostate and changes in the breast and endometrium) with the highest doses (4.75 mg / kg for progestin and 47.5 mg / kg for estrogen) are those related to the pharmacodynamic action of the components.
Tests on rats have shown a clear interference with fertility up to its suppression, in relation to the doses of estrogen-progestin used.
Adequate studies have shown the absence of teratogenic, embryotoxic effects and peri- or postnatal toxicity.
Mutagenicity tests were negative and carcinogenicity tests conducted on mice and rats for 24 months gave results similar to that found with similar compounds.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose; cornstarch; povidone 25,000; sodium calcium edetate; magnesium stearate, sucrose; povidone 700,000; macrogol 6,000; calcium carbonate; talc; ethylene glycol ester of montanic acid (E wax).
06.2 Incompatibility
There are no known incompatibilities
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store at a temperature not exceeding 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
PVC blister with 21 coated tablets.
06.6 Instructions for use and handling
See sect. 4.2.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l., Via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
A.I.C. n. 026286029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
24 October 1988/31 May 2010
10.0 DATE OF REVISION OF THE TEXT
26/02/2013
11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY
12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL
CHECKLIST FOR PRESCRIPTORS - COMBINED HORMONAL CONTRACEPTIVES
Please use this checklist together with the Summary of Product Characteristics during any consultation on Combined Hormonal Contraceptives (COCs).
• The thromboembolism (eg deep vein thrombosis, pulmonary embolism, heart attack and stroke) represents an important risk associated with the use of COCs.
• The risk of thromboembolism with a CHC is higher:
- during the first year d "employment;
- when you leave resume use after a break in intake of 4 or more weeks.
• COCs containing ethinylestradiol in combination with levonorgestrel, norgestimate or norethisterone have the lower risk to cause venous troembolism (VTE).
• The risk for a woman also depends on her baseline risk of thromboembolism. The decision to use a COC must therefore take into account the contraindications and individual risk factors, particularly those relating to thromboembolism - see the boxes below and the relevant Summary of Product Characteristics.
• The decision to use any CHC rather than one with the lowest risk of venous thromboembolism (VTE) should only be made after an interview with the woman to ensure she understands:
- the risk thromboembolism associated with its COC;
- the effect of any risk factor inherent in his risk of thrombosis;
- which must pay particular attention to signs and symptoms of a thrombosis.
Remember that a woman's risk factors can vary over time. It is therefore important to use this checklist at every consultation.
• You need surgery;
• It is necessary that you undergo a prolonged period of immobilization (as in the case of an accident or illness, or for a "cast in a lower limb).
→ In these cases it would be better to reconsider whether or not to use a non-hormonal contraceptive until the risk returns to normal..
• Travel for an extended period (> 4 hours);
• Develop any of the contraindications or risk factors for combined contraceptives;
• She has given birth in the last few weeks.
→ In such situations, your patient should pay particular attention to catch any signs and symptoms of thromboembolism.
Please strongly encourage women to read the Package Insert that accompanies each COC pack, including the symptoms of thrombosis which they should carefully watch out for.
Please report any suspected adverse reactions from COC to the territorially competent Pharmacovigilance Offices or to the AIFA as required by current legislation
IMPORTANT INFORMATION ABOUT COMBINED ORAL CONTRACEPTIVES (COCS) AND THE RISK OF BLOOD CLOTS
All combined contraceptives increase the risk of having a blood clot. The overall risk of a blood clot from taking a combined hormonal contraceptive (COC) is small., but clots can represent a serious condition and in very rare cases even fatal.
It is very important that you recognize when you may be at a higher risk for a blood clot, what signs and symptoms to watch out for and what actions you need to take.
In which situations is the risk of a blood clot higher?
- during the first year of use of a COC (including when resuming use after an interval of 4 or more weeks)
- if you are overweight
- if you are over 35 years of age
- if you have a family member who has had a blood clot at a relatively young age (i.e. under 50)
- if you have given birth in the last few weeks
Self smokes and over 35 years of age, she is strongly advised to stop smoking or to use a non-hormonal method of contraception.
See a doctor immediately if you experience any of the following symptoms:
• Severe pain or swelling in one of the legs which may be accompanied by flaccidity, warmth or changes in the color of the skin such as the appearance of paleness, redness or bluish color. He could have deep vein thrombosis.
• The sudden and unexplained shortness of breath or onset of rapid breathing; severe chest pain which may increase with deep breathing; a sudden cough with no obvious cause (which can produce blood). It could be a serious complication of deep vein thrombosis called pulmonary embolism. This occurs if the blood clot migrates from the leg to the lung.
• A pain in the chest, often sharp, but which sometimes occurs such as malaise, a sense of pressure, weight, upper body discomfort radiating to the back, jaw, throat, arm with a feeling of fullness associated with indigestion or choking, sweating, nausea, vomiting or dizziness . It could be a heart attack.
• A numbness or a sense of weakness in the face, arm or leg, especially on one side of the body; a difficulty in speaking or understanding; a "sudden confusion of mind, a sudden loss of vision or blurred vision; a headache / migraine intense and worse than usual. This could be a stroke.
Look out for symptoms of a blood clot, especially if:
• has just had surgery
• you have been immobilized for a long time (such as due to an accident or illness, or because you have had your leg in a cast)
• has traveled a long way (for more than 4 hours)
Remember to tell your doctor, nurse or surgeon that you are taking a combined hormonal contraceptive if:
• You have had or are due to have surgery
• There is any situation where a healthcare professional asks you what medications you are taking
For more information, please read carefully the Package Leaflet accompanying the drug and immediately report any undesirable effects associated with the use of the combined hormonal contraceptive to your doctor or pharmacist.
