Active ingredients: Levonorgestrel, Ethinylestradiol
LOETTE 0.1 mg + 0.02 mg coated tablets
Why is Loette used? What is it for?
Pharmacotherapeutic group
LOETTE is a combined type contraceptive for oral use. Each tablet contains two different female hormones: levonorgestrel 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.
Contraindications When Loette should not be used
The combination pill should not be used if any of the following conditions are present. If these are present, it is important to inform your doctor.
- Disorders, present or past, of the venous and arterial circulation, in particular those related to thrombosis. Thrombosis is the formation of a blood clot that can occur in the blood vessels of the legs (deep vein thrombosis), the lungs (pulmonary embolism), the heart (heart attack), the brain (stroke), or elsewhere in the body ( see also the section "Thrombosis").
- Conditions, present or past, which may be a first sign of heart attack (such as angina pectoris or chest pain) or stroke (such as transient ischemic attack).
- Hereditary or acquired predisposition for venous or arterial thrombosis
- Headache with focal neurological symptoms, such as aura.
- Diabetes mellitus with blood vessel injury.
- Jaundice (yellowing of the skin) or severe liver disease, present or past.
- Current or previous pancreatitis if associated with severe hypertriglyceridemia
- Tumor of the breast or of the 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 Loette
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 the control of blood pressure, the examination of the breasts, abdomen and general gynecology 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, LOETTE does not protect against HIV infection (AIDS) or any other sexually transmitted disease.
LOETTE 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 LOETTE. 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 "Interactions").
Interactions What medications or foods can change the effect of Loette
Inform your doctor or pharmacist that you have recently taken any other medicines, even those without a prescription.
Some drugs can prevent "effective action of the pill. 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 prescribing doctor about any medications you are already taking, and also inform any other doctors or dentists prescribing other medications that you are using LOETTE, so 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 so in case of ascertained intolerance to sugars contact your doctor before taking the medicine.
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
Thrombosis
The use of any combined oral contraceptive carries an increased risk of venous thromboembolic events (VTE), such as deep vein thrombosis and pulmonary embolism, compared with no use. The excess 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)
The overall absolute risk (incidence) of VTE for COCs containing levonorgestrel with 30 µg ethinyl estradiol is approximately 20 cases per 100,000 woman-years of use.
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). They are extremely rare in the liver, intestines, kidneys and eyes.
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.
The risk of deep vein thrombosis increases temporarily in the case of surgery or prolonged immobilization (for example in the case of a cast or bandage of the legs). In women taking the Pill, the risk may be even greater. Inform the doctor of the use of the pill well before any hospitalization or planned surgery. The doctor may ask to stop the pill at least 4 weeks before the surgery which increases the risk of thrombosis or at the time of immobilization and decide to resume it not before 2 weeks have passed since the recovery of mobility (complete recovery).
Cases of retinal thrombosis have been reported during the use of COCs. If there is unexplained partial or complete loss of vision, onset of proptosis or diplopia, papillary edema or vascular lesions of the retina, use of COC must be discontinued and the cause must be evaluated immediately.
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").
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 cholestasis related to COCs 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, oral contraceptives. combined must be stopped.
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.
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 "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
A "glucose intolerance was recorded in patients using combined oral contraceptives.
Although COCs may affect peripheral insulin resistance and glucose tolerance, there is no evidence for the need for regimen adjustment in diabetic patients using COCs. Diabetic patients or patients with a "glucose intolerance" should be carefully followed (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 amount of progestogen 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 arterial hypertension or with hypertension-related diseases or kidney disease, with a history of arterial hypertension. 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 experience 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 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 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, decrease in resin absorption of free T3), adrenal (increase in plasma cortisol, increase in cortisol-binding globulin, decrease in dehydroepiandrosterone sulfate) and renal (increase in plasma creatinine and decrease in creatinine clearance), plasma levels of 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
LOETTE 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").
LOETTE is not recommended while breastfeeding.
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.
Effects on ability to drive and use machines
LOETTE 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 Loette: Dosage
How to take LOETTE
Each pack of LOETTE 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 one of the boxes of the calendar pack marked with the day of the week on which treatment is started. For example, if the treatment starts on Friday, take one tablet marked Friday. 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 less.
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 LOETTE on day 8, even if the bleeding is still ongoing.This means that the second pack of LOETTE 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 LOETTE on the first day of your period, which is the first day of your period, taking the tablet marked with that day of the week. For example, if your period starts on Friday, take the pill marked Friday. Then continue in order. indicated by arrows. It 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 tablet-taking in the first cycle.
Switching from another "combined type" pill.
You can start taking LOETTE the day after the last pill of the previous contraceptive (ie without observing any interval). If your previous contraceptive pack also contains inactive tablets, you can take LOETTE 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 LOETTE 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 or implantation contraceptive or an intrauterine device.
Start using LOETTE 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. However, in the former. seven days of taking the tablets 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 the 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 to take LOETTE.
If you are breastfeeding and want to take LOETTE, talk to your doctor first.
After a spontaneous or induced abortion.
Follow your doctor's prescription.
Termination of employment
You can stop using LOETTE 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 LOETTE 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.
1. 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
2. Discontinue the 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 LOETTE, 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 Loette
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 LOETTE, notify your doctor immediately or go to the nearest hospital.
If you have any further questions on the use of LOETTE, ask your doctor or pharmacist
Side Effects What are the side effects of Loette
Like all medicines, LOETTE 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 "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 paragraph "Precautions for use": "Thrombosis" and "Cancer";
- 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.
COC use 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.
- 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)
- 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.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
See the expiry date indicated on the package. The expiry date refers to the last day of the month.
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 below 25 ° C, away from excessive heat and humidity.
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
Each tablet contains: active ingredients: levonorgestrel 0.100 mg; ethinyl estradiol 0.02 mg.
Excipients: lactose, microcrystalline cellulose, polacrilin potassium, magnesium stearate, macrogol, hypromellose, titanium dioxide, synthetic red iron oxide, ethylene glycol ester of montanic acid (E wax).
Pharmaceutical form and content
Aqueous film-coated tablets for oral use.
Carton containing 1 calendar pack of 21 coated tablets.
Carton containing 3 calendar packs 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
LOETTE 0.100 MG + 0.02 MG COATED TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each coated tablet contains
Active ingredients: levonorgestrel 0.100 mg and ethinyl estradiol 0.02 mg.
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Aqueous film-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 LOETTE 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 one of the boxes of the calendar pack marked with the day of the week on which treatment is started. For example, if treatment starts on Friday, take one tablet marked Friday.
The next tablet must be taken the next day from the nearby 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 always at the same time, preferably after the evening meal.
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 LOETTE 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 LOETTE
No hormonal contraceptive treatment in the previous month
The intake of LOETTE tablets should start on the 1st day of the woman's natural cycle (ie the first day of menstruation).
It is also possible to start LOETTE between the 2nd and 5th day of the cycle but, during the first cycle it is recommended to also use a non-hormonal barrier method of contraception (such as condoms and spermicides) for the first 7 days of taking the tablets. LOETTE.
Changing from another combined oral contraceptive
The first tablet of LOETTE should preferably be taken the day after the last active tablet of the previous contraceptive or, at the latest, the day after the usual pill-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 LOETTE must start the next day. In the case of an implant, the intake of LOETTE must begin on the same day that the progestogen-only implant or 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. hormonal for the first seven days of taking the LOETTE tablets.
After a first trimester abortion
You can start treatment with LOETTE 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, LOETTE should not be started before the 21st-28th day postpartum in non-breastfeeding mothers or after a second-trimester abortion. She should also be advised to also use a supportive non-hormonal method of contraception during the first seven days of taking the LOETTE tablets. However, if intercourse has occurred in the meantime, before actually starting to take LOETTE, pregnancy or pregnancy should be ruled out. the onset of the first menstruation should be awaited (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 you are less than 12 hours late in taking any tablet 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 you are more than 12 hours late in taking any tablet from the usual time or if you have not taken 2 or more tablets, 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 2 tablets on the same day. Subsequent tablets should be taken at the usual time. In addition, a non-hormonal method of contraception (e.g. condom) 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 2 tablets in one day 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 missed 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 2 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 forgotten, and then continue with a tablet-free interval. new packaging.
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. In this case, the recommendations outlined in the section "IRREGULAR TABLETS" should be considered if necessary. If the usual dosing schedule is not to be changed, one or more required extra tablets should be taken from a new pack.
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 pathology in history (deep vein thrombosis, pulmonary embolism), with or without triggering factors;
• 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 pathologies 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 undetermined 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 preparation must be stopped immediately.
04.4 Special warnings and appropriate precautions for use
PRECAUTIONS D "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" (section 4.4); The examination should be repeated, during the use of COCs, at least once a year. A PAP test 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 must be individually adapted 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.
LOETTE contains lactose so no It should be used by patients with hereditary galactose intolerance, Lapp lactase deficiency or in the case of glucose / galactose malabsorption syndrome.
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 estrogen and progestogen compatible with a low degree 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)
The overall absolute risk (incidence) of VTE for COCs containing levonorgestrel with 30 mcg ethinyl estradiol is approximately 20 cases per 100,000 woman-years of use.
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 currently using COCs have a slightly increased relative risk of breast cancer (RR = 1.24) and that the increased risk gradually disappears over the next 10 years. 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 should be closely monitored and, if cholestasis recurs, the COC 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 contraceptive Combined oral therapy should be discontinued and cause should be evaluated 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
A 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 adjustment of the treatment regimen in diabetic patients who they use combined oral contraceptives. However, patients with diabetes or glucose intolerance should be closely monitored while taking the COC (see section 4.4).
A small percentage of women when taking a COC experience changes in lipid values. 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 effects of single doses of estrogen and progestogen as well as the nature and total amount of progestogen 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.
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 or kidney disease or with 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 pill-free interval. If the COC has been taken as described in section 4.2, it is unlikely that the pregnancy is established. However, if prior to the withdrawal bleeding the 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 effectiveness 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 diarrhea ") 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).
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.
Ethinylestradiol 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 affect the results of some laboratory tests including biochemical tests of liver function (reduction of bilirubin and alkaline phosphatase), thyroid (increase in total T3 and T4 due to an increase in TBG, decrease 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 protein levels transport, 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.
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).
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
LOETTE 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 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 artery disease;
• hyperlipidemia (hypertriglyceridaemia and / or hypercholesterolemia)
• severe mastodynia, benign mastopathy;
• intense and unusual headaches, migraines, dizziness, changes in vision;
• exacerbation of epilepsy;
• hepatocellular carcinoma, cholestatic jaundice, hepatocellular damage (eg hepatitis, impaired liver function);
• 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, enlargement, 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
• breast cancer diagnosis.
• benign liver tumors (eg 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; deprivation haemorrhage.
There are no specific antidotes and any further treatment must be symptomatic
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: systemic oral contraceptives; fixed estrogen-progestogen associations.
ATC code: G03AA07
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 mg ethinylestradiol or 50 mcg 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
Levonorgestrel, in various galenic formulations, is rapidly and completely absorbed.
Levonorgestrel undergoes a minimal "first pass effect" and is almost completely bioavailable after oral administration.
The elimination half-life of levonorgestrel in combination with ethinylestradiol is approximately 36 ± 13 hours at steady-state.
In serum, levonorgestrel is almost exclusively bound to proteins and only a minor fraction of the drug is present in free form.
The increase in SHBG on the one hand and the high degree of binding affinity of levonorgestrel to this protein on the other are the main factors responsible for the accumulation of the drug in the serum, as well as for the prolongation of the half-life of levonorgestrel.
Levonorgestrel is metabolised mostly through reduction, hydroxylation and conjugation to glucuronide and sulfate.
The metabolites of levonorgestrel are excreted in urine (43-45%) and faeces (32%) with a half-life of approximately 24 hours.
Ethinylestradiol is rapidly and almost completely absorbed after oral administration. Due to a strong "first pass effect", the mean bioavailability of ethinylestradiol is approximately 43%, with significant individual variations.
After repeated oral administration, serum levels of ethinylestradiol increase by approximately 30-50%, reaching steady-state in the second half of each treatment cycle.
Ethinylestradiol is extensively bound to albumin (approximately 98%) but not to SHBG.
28-54% of ethinylestradiol is excreted metabolised in the urine and approximately 30% in the faeces.
The half-life of renal excretion of ethinylestradiol associated with levonorgestrel is approximately 18 hours.
05.3 Preclinical safety data
Animal toxicity studies for human risk assessment were performed both on each component of the preparation, ethinylestradiol and levonorgestrel, and on their combination.
Acute toxicity studies did not indicate any risk of acute side effects in case of accidental ingestion of multiples of the daily contraceptive dose.
No effects that could indicate an unexpected risk for humans were observed during systemic tolerance studies after repeated administration.
Long-term toxicity studies with repeated doses for the evaluation of a possible oncogenic activity have not shown an oncogenic potential in the case of a therapeutic use of the preparation in man. However, it should be kept in mind that sexual steroids can promote the growth of some hormone-dependent tissues and tumors.
Studies of embryotoxicity and teratogenicity of ethinylestradiol and the evaluation in animals of the effects of the combination on fertility, fetal development, lactation and reproductive behavior of the offspring did not indicate a risk of adverse reactions in humans following the appropriate use of the product. In the event of inadvertent use of the product after the onset of pregnancy, treatment should be stopped immediately.
In vitro and in vivo studies conducted with ethinylestradiol and levonorgestrel did not reveal a mutagenic potential.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose, microcrystalline cellulose, polacrylin potassium, magnesium stearate, macrogol, hypromellose, titanium dioxide, synthetic red iron oxide, E wax (ethylene glycol ester of montanic acid).
06.2 Incompatibility
Not relevant
06.3 Period of validity
2 years.
06.4 Special precautions for storage
Store at a temperature below 25 ° C away from excessive heat and humidity.
06.5 Nature of the immediate packaging and contents of the package
PVC / aluminum blister
Cardboard box
Packaging:
Carton containing 1 calendar-box of 21 coated tablets.
Carton containing 3 calendar packs of 21 coated tablets.
06.6 Instructions for use and handling
See section 4.2
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l., Via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 033161011 - pack of 1 blister
AIC n. 033161023 - pack of 3 blisters
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
23.07.2008
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of 26/02/2013
