Active ingredients: Desogestrel
NACREZ 75 micrograms film-coated tablets
Why is Nacrez used? What is it for?
NACREZ is used to prevent pregnancy. It contains a small amount of a type of female sex hormone, the progestin desogestrel. For this reason, NACREZ is called a progestogen-only pill (POP) or a minipill. Unlike the combined pill, the POP or minipill does not contain an estrogen hormone along with the progestin.
Most POPs or minipills work primarily by preventing sperm from reaching the uterus; they do not always prevent the egg cell from maturing, which is the main action of combination pills. NACREZ differs from other minipills in having a dose that in most cases is high enough to prevent the egg cell from maturing. Consequently, NACREZ guarantees a "high contraceptive efficacy.
In contrast to the combined pill, NACREZ can be used by women who are intolerant to estrogen and those who are breastfeeding. A disadvantage is vaginal bleeding which can occur at irregular intervals while using NACREZ. It is also possible not to have any bleeding.
Contraindications When Nacrez should not be used
Do not take NACREZ
- if you are allergic (hypersensitive) to the active substance desogestrel or to any of the other ingredients of NACREZ.
- if you are pregnant or think you may be.
- if you have thrombosis. Thrombosis is the formation of a blood clot in a blood vessel (eg in the legs (deep vein thrombosis) which can, among other things, migrate into the lungs and cause a "pulmonary embolism).
- if you have or have had jaundice (yellowing of the skin) or severe liver disease and your liver function has not yet returned to normal.
- if you have or suspect that you have cancer that is sensitive to sex steroids, such as some types of breast cancer.
- if you have any unexplained vaginal bleeding.
Precautions for use What you need to know before taking Nacrez
Talk to your doctor before taking NACREZ if you have any of these conditions. Your doctor may advise you to use a non-hormonal method of contraception. Consult your doctor immediately if any of these conditions appear for the first time while using NACREZ.
Take special care with NACREZ
- if you have ever had breast cancer.
- if you have liver cancer, as a possible effect of NACREZ on liver cancer cannot be excluded.
- if you have changes in liver function.
- if you have had a thrombosis.
- if you have diabetes.
- if you suffer from epilepsy (see section 2 "Taking other medicines").
- if you suffer from tuberculosis (see section 2 "Taking other medicines").
- if you have high blood pressure or your blood pressure rises significantly.
- if you have or have ever had chloasma (yellowish-brown pigmented spots on the skin, especially on the face); if so, avoid too much exposure to the sun or ultraviolet radiation.
Talk to your doctor if you have any of these conditions. If NACREZ is taken in the presence of any of these conditions, it may be necessary to monitor it closely. Your doctor can tell you what to do.
Regular checkups
While taking NACREZ, your doctor may tell you to have regular checkups. Generally, the frequency and nature of these visits will depend on your personal situation.
Contact your doctor as soon as possible
- if you have sharp pain or swelling in your leg, unexplained chest pain, breathlessness, unusual cough, particularly if the cough is accompanied by blood (these may indicate thrombosis or embolism, respectively);
- if you experience sudden severe pain in your stomach or if you get a yellowish color (jaundice) (which may indicate liver problems);
- if you feel a lump in your breast (could indicate breast cancer);
- if you experience sudden or sharp pain in the lower abdomen or stomach area (this could indicate an ectopic pregnancy, ie a pregnancy outside the womb);
- if you need to remain immobilized or undergo surgery (consult your doctor at least four weeks in advance);
- if you have unusual and heavy vaginal bleeding;
- if you suspect you are pregnant.
Interactions Which drugs or foods can change the effect of Nacrez
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Some medicines can stop NACREZ from working properly and can cause unexpected bleeding or reduce its effectiveness in preventing pregnancy. These include medicines used to treat:
- epilepsy (e.g. primidone, phenytoin, carbamazepine, oxcarbazepine, felbamate, topiramate and phenorbital),
- tuberculosis (e.g. rifampicin, rifabutin),
- HIV infections (e.g. ritonavir, nelfinavir),
- o other infectious diseases (e.g. griseofulvin), gastric disturbances (medicinal charcoal), depressed mood (the herbal preparation based on St. John's wort),
- in case of transplants (eg cyclosporine).
Tell your doctor if you are taking any other medicines, including herbal medicines. Also tell any other doctor or dentist who prescribes another medicine (or the pharmacist) that you are taking NACREZ. They will be able to tell you if you need to take additional contraceptive measures (such as a condom) and for how long. NACREZ can also affect the way some medicines work in the body, causing either an increase in effect (eg for medicines containing cyclosporine) or a decrease in effect.
Taking NACREZ with food and drink
NACREZ can be taken with or without food and drink
Warnings It is important to know that:
Breast cancer
Check your breasts regularly and contact your doctor as soon as possible if you feel a lump in your breast.
Breast cancer has been observed slightly more frequently in women who take the pill than in women of the same age who do not take the pill. If the pill is stopped, the risk gradually decreases. 10 years after stopping, the risk is the same as in women who have never taken the pill. Breast cancer is rare under the age of 40, but the risk increases as we age. Therefore, the excess number of breast cancer diagnoses is greater if the age to which the woman takes the Pill is higher. The duration of taking the Pill is a less important factor.
For every 10,000 women who take the Pill for up to 5 years but stop taking it before the age of 20, there will be less than 1 additional case of breast cancer diagnosed up to 10 years after stopping it, in addition to 4 cases normally diagnosed in this age group.
Similarly, for every 10,000 women who take the pill for up to 5 years but stop taking the pill before age 30, there will be 5 additional cases in addition to the 44 cases normally diagnosed. For every 10,000 women who take the pill for one maximum duration of 5 years, but they stop taking it before the age of 40, there will be 20 additional cases in addition to the 160 cases normally diagnosed.
The risk of breast cancer in users of progestogen-only pills such as NACREZ is believed to be similar to that in women who also use pills that also contain estrogen (combination pills), but the evidence is less conclusive.
Breast cancer seen in women who take the Pill appears to have spread less than breast cancer seen in women who do not take the Pill. It is not known whether or not the difference in breast cancer risk is caused by the pill. It is possible that the cancer was diagnosed earlier because women had more frequent checks.
Thrombosis
See your doctor immediately if you notice possible signs of thrombosis. To find out what these possible signs are, see the section "Contact your doctor as soon as possible", first point.
Thrombosis is the formation of a blood clot that can block a blood vessel. Thrombosis sometimes occurs in the deep veins of the legs (deep vein thrombosis). If the clot breaks away from the veins in which it has formed, it can travel to the arteries of the lungs and block them. This causes the so-called "pulmonary embolism". As a result, life-threatening and death-threatening situations can arise. Deep vein thrombosis is a rare event. It can develop regardless of whether you take the pill or not. It can also occur if you are pregnant.
The risk of having a thrombosis is higher in pill users than in non-users. The difference in thrombosis risk with progestogen-only pills such as NACREZ versus pills that also contain estrogen (combination pills) is not known.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
Do not use NACREZ if you are pregnant or if you think you may be.
Feeding time
NACREZ can be used during breastfeeding.
If you are breast-feeding and want to use NACREZ, please consult your doctor.
Driving and using machines
NACREZ does not affect the ability to drive or use machines. Important information about some of the ingredients of NACREZ
NACREZ contains lactose (milk sugar).
If you know you are intolerant to some sugars, consult your doctor before taking this medicine.
Dose, Method and Time of Administration How to use Nacrez: Posology
Always take NACREZ exactly as your doctor has instructed you as described in this leaflet. If in doubt, consult your doctor or pharmacist.
Method of administration
- the NACREZ pack contains 28 tablets.
- take one tablet a day.
- Swallow the tablet whole with an adequate amount of water.
Arrows are printed between the tablets on the front of the pack. If you turn the package upside down and look at the back, you will find the days of the week printed on the film.
Each day corresponds to one tablet. Each time you start a new pack of NACREZ, take one tablet from the top row. Don't start with just any tablet. For example, if you start on a Wednesday, you have to take the tablet from the first row marked "Wed" (on the back). Keep taking one tablet a day until the pack is finished. Always follow the direction indicated by the arrows. By looking at the back of the pack you can easily check if you have already taken the tablet on a specific day.
Take the tablet at about the same time every day so that the interval between tablets is always 24 hours. You may experience bleeding while using NACREZ, but you must continue to take the tablets regularly.When you have finished one pack, start the new NACREZ pack the next day, so without interruption and without waiting for bleeding to occur.
Starting the first pack of NACREZ
- If you have not used a hormonal contraceptive in the previous month
Wait for your period to start. On the first day of your period, take the first tablet of NACREZ. You must not take any additional contraceptive measures. additional contraceptive (barrier method, e.g. condom) for the first 7 days of taking the tablets.
- Changing from a combination pill, vaginal ring, or transdermal patch
You can start taking NACREZ the day after taking the last tablet of the pill pack you are currently taking or the day you have removed the vaginal ring or patch (which means no pill, ring or patch-free interval). If the pill pack you are taking also contains inactive tablets, you can start NACREZ the day after "taking the last active tablet" (if you are not sure which this is, ask your doctor or pharmacist). If you follow these instructions , you must not take any additional contraceptive measures. You can also start at the latest the day after the pill, ring or patch-free interval or after taking the inactive tablets of your current contraceptive. If you follow these instructions, you must use a method. additional contraceptive (barrier method, for example condoms) for the first 7 days of taking the tablets.
- Switching from another progestogen-only pill (minipill) to NACREZ
You can stop taking your current pill any day and start taking NACREZ right away. You do not need to take any additional contraceptive measures.
- Changing from an injectable, implant, or progestogen-releasing intrauterine device (IUS) to NACREZ
Start using NACREZ when you need to have your next injection or on the day of removal of the implant or IUS. You must not take any additional contraceptive measures.
- After a birth
After having a baby, you can start taking NACREZ before your period returns. If it starts more than 21 days after giving birth, you must use an additional method of contraception during the first cycle (barrier method, such as a condom) for the first 7 days of taking the tablets. However, if you have had sexual intercourse in the meantime, you must make sure that you are not pregnant before you start using NACREZ.
- After a spontaneous or induced abortion
Follow your doctor's advice. NACREZ, like all hormonal contraceptives, offers no protection against HIV infection (AIDS) or any other sexually transmitted disease.
If you forget to take NACREZ
If you take a tablet less than 12 hours late, the protection of NACREZ is maintained. Take the forgotten tablet as soon as you remember and then take the next tablet at the usual time. If you take a tablet more than 12 hours late, the protection of NACREZ may be reduced. The more tablets you miss, the more the greater the risk of reduced contraceptive efficacy. Take the last missed tablet as soon as you remember and then take the next tablets at the usual time. This could also mean taking two tablets on the same day. Also use an additional method of contraception (such as a condom) for the next 7 days of taking the tablets. If you have forgotten one or more tablets during the first week of taking and had sex in the previous week, there is a possibility that you may become pregnant. Ask your doctor for advice.
If you suffer from gastrointestinal complaints (e.g. vomiting or severe diarrhea)
If you vomit or have severe diarrhea or if you use medicinal charcoal within 3-4 hours of taking the NACREZ tablet, it is possible that the active substance has not been completely absorbed and therefore the effectiveness of NACREZ is reduced. In this case, you must use additional contraceptive methods (such as condoms) for the next 7 days. Take the next tablet at the usual time.
If you stop taking NACREZ
You can stop taking NACREZ at any time. You are no longer protected against pregnancy from the day you stop taking it.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Nacrez
There have been no reports of serious harmful effects from taking too many tablets containing desogestrel at the same time. Symptoms that may occur are nausea, vomiting and, in young women, mild vaginal bleeding. For more information ask your doctor.
Side Effects What are the side effects of Nacrez
Like all medicines, NACREZ can cause side effects, although not everybody gets them.
Serious side effects associated with the use of NACREZ are described in subsections "Breast cancer" and "Thrombosis" in section 2 "Before you take NACREZ." Read this section carefully for more information and contact your doctor immediately if necessary.
Vaginal bleeding may occur at irregular intervals while using NACREZ. It may be light discharge that does not require any type of sanitary pad or more profuse bleeding, similar to low menstruation, which requires sanitary pads. It is also possible not to have any bleeding. These irregular bleeding do not indicate a decrease in the contraceptive protection of NACREZ. It is generally not necessary to take any measures.
Continue to take NACREZ. However, if bleeding is heavy or prolonged, consult your doctor.
The classification of undesirable effects is based on the following frequency data:
- Very common: affects more than 1 in 10 people
- Common: affects 1 to 10 in 100 people
- Uncommon: affects 1 to 10 in 1,000 people
- Rare: affects 1 to 10 in 10,000 people
- Very rare: affects less than 1 in 10,000 people
- Frequency not known: frequency cannot be estimated from the available data
The following side effects have been reported by users of desogestrel:
In addition to these side effects, breast discharge may also occur.
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
Keep out of the reach and sight of children.
Do not use NACREZ after the expiry date which is stated on the carton. The expiry date refers to the last day of the month.
NACREZ does not require any special storage conditions.
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.
Deadline "> Other information
What NACREZ contains
- The active ingredient is: desogestrel (75 micrograms).
- The other ingredients are: lactose monohydrate (see also "Important information about some of the ingredients of NACREZ" in section 2), maize starch, povidone, stearic acid, all-rac-alpha-tocopherol, silica colloidal anhydrous, hypromellose, macrogol 400, talc, titanium dioxide.
Description of what NACREZ looks like and contents of the pack
NACREZ tablets are white to off-white, circular, biconvex, 5.4-5.8 mm in diameter, unmarked.
One blister pack of NACREZ contains 28 film-coated tablets. Each carton contains 1, 3 or 6 blister packs, each individually packed in a sachet.
Not all pack sizes may be marketed.
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 -
NACREZ 75 MCG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each film-coated tablet contains 75 mcg of desogestrel.
Excipient with known effect:
Each film-coated tablet contains 54.35 mg of lactose monohydrate.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Film-coated tablet.
White to off-white, circular, biconvex tablets, 5.4-5.8 mm in diameter, unmarked.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Oral contraception.
04.2 Posology and method of administration -
Dosage
How to start NACREZ
No hormonal contraceptive treatment (in the previous month)
Taking the tablets should start on the first day of the natural menstrual cycle (ie the first day of menstruation). It is also possible to start between the second and fifth day of the cycle, but, in this case, during the first cycle it is recommended to also employ a barrier method in the first seven days of tablet-taking.
After a first trimester abortion
After a first trimester abortion it is recommended to start treatment immediately. In this case it is not necessary to use an additional method of contraception.
After childbirth, premature birth or second-trimester abortion
After delivery, contraceptive treatment with NACREZ can be started before menstruation has returned. If more than 21 days have elapsed since delivery, pregnancy must be ruled out and an additional method of contraception used in the first week (see section 4.6).
How to start NACREZ when coming from another contraceptive method
Changing from a combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or transdermal patch).
The woman should start NACREZ preferably on the day after the last active tablet (the last tablet containing the active substances) of the previous combined oral contraceptive (COC) or on the day of removal of the vaginal ring or transdermal patch. the use of an additional contraceptive method is necessary. Not all contraceptive methods may be available in all countries of the European Union.
The woman can also start the day after the usual pill, patch or ring-free interval at the latest or the day after the last placebo tablet of the previous combined hormonal contraceptive, but it is recommended to use an additional barrier method during the first few 7 days of taking the tablets.
Changing from a progestogen-only method of contraception (minipill, injection, implant, or progestogen-releasing intrauterine device [IUS])
The woman can switch at any time from the minipill (in the case of a progestogen-releasing implant or intrauterine device, the day the implant or device is removed or, in the case of an injectable, the day she should be given the next injection).
Management of forgotten tablets
Contraceptive protection may be reduced if more than 36 hours have elapsed between taking two tablets. If you are less than 12 hours late in taking any tablet, the forgotten tablet should be taken as soon as you remember. ; the next one must be taken according to the usual scheme.
If the delay is more than 12 hours, the woman must use additional contraception for the next 7 days. If you forgot to take tablets in the first week and have had sexual intercourse in the previous week, the possibility that you are pregnant should be considered.
Advice in case of gastrointestinal disorders
In the event of a severe gastrointestinal disturbance, absorption may not be complete and additional contraceptive measures must be taken.
If vomiting occurs within 3-4 hours of taking the tablet, absorption may not be complete. In this case, the advice on forgotten tablets given in this section applies.
Treatment monitoring
Before prescribing the product it is necessary to carry out a thorough medical history; a careful gynecological examination is also recommended to rule out an ongoing pregnancy. Before prescribing the product, cycle disorders such as oligomenorrhea and amenorrhea should be evaluated.
The interval between medical check-ups is a function of each individual case. If the prescribed product is likely to influence a latent or manifest disease (see section 4.4), related medical check-ups should be scheduled.
Even when NACREZ is taken regularly, cycle disturbances can occur. If bleeding is very frequent and irregular, another method of contraception should be considered. If symptoms persist, an organic cause must be ruled out.
In case of amenorrhea during therapy it is necessary to investigate whether or not the tablets have been taken according to the instructions; in this case, a pregnancy test may also be indicated.
In the event of pregnancy, the treatment should be discontinued.
Women should be advised that NACREZ does not protect against HIV infection (AIDS) or other sexually transmitted diseases.
Pediatric population
The safety and efficacy of desogestrel in adolescents below 18 years have not been established. No data are available.
Method of administration
The tablets should be taken at approximately the same time each day with a small amount of liquid, so that the interval between two tablets is always 24 hours. The first tablet should be taken on the first day of your period. It should then be continued with one tablet a day, every day, even if any vaginal bleeding occurs. Each new blister should be started directly the day after the previous blister has ended.
04.3 Contraindications -
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
- Venous thromboembolic disorders in progress.
- Previous or current severe liver disease, until liver function values have returned to normal.
- Known or suspected malignant diseases sensitive to sex steroids.
- Undiagnosed vaginal bleeding.
04.4 Special warnings and appropriate precautions for use -
If any of the following risk factors / conditions are present, the benefits of using the progestogen should be weighed against the possible risks of each individual case and discussed with the woman before deciding to initiate NACREZ. In case of aggravation. , exacerbation or first appearance of any of these conditions, the woman should contact her physician. The physician should then decide whether the use of NACREZ should be discontinued.
The risk of breast cancer typically increases with advancing age. During the use of combined oral contraceptives (COCs) the risk of being diagnosed with breast cancer is slightly increased. This increased risk gradually disappears over 10 years after stopping the combined oral contraceptive and does not depend on the duration of use, but by the age of the woman while taking the COC. The expected number of cases diagnosed per 10,000 women using COCs (up to 10 years after stopping treatment) compared with women who have never done contraceptive use over the same time period was calculated in the respective age groups and is shown in the table below:
The risk in women using progestogen-only contraceptives, such as NACREZ, is likely to be similar to that associated with taking COCs. However, for progestogen-only contraceptives the evidence is less conclusive. The increase in COCs. risk associated with COCs is low compared with the risk of being diagnosed with breast cancer later in life. Breast cancer diagnosed in COC users tend to be less advanced than in COC users. The increased risk in women using COCs may be due to an earlier diagnosis, the biological effects of the pill, or a combination of both.
As a biological effect of progestogens on liver cancer cannot be excluded, an individual benefit / risk assessment should be made in women with liver cancer.
In the event of acute or chronic disturbances of liver function, the woman should be advised to consult a specialist for medical examination and consultation.
Epidemiological studies have shown the association between the use of combined oral contraceptives and an increased incidence of venous thromboembolism (VTE, deep vein thrombosis and pulmonary embolism). Although the clinical relevance of this finding for desogestrel used as a contraceptive in the absence of an estrogen component is unknown, treatment with NACREZ should be discontinued in the event of thrombosis. Interruption of NACREZ treatment should also be considered in the event of prolonged immobilization following surgery or illness. Women with a history of thromboembolic disorders should be advised of the possibility of the disease returning.
Although progestogens may affect peripheral insulin resistance and glucose tolerance, there is no evidence for the need to change the treatment regimen in diabetic women using a progestogen-only pill. However, diabetic patients should be closely monitored. during the first months of use.
If sustained hypertension develops during use of NACREZ or if a significant increase in blood pressure does not respond adequately to antihypertensive therapy, discontinuation of NACREZ should be considered.
Treatment with NACREZ causes a reduction in serum levels of estradiol to values corresponding to the initial follicular phase. It is not yet known whether this reduction has a clinically relevant effect on bone mineral density.
With traditional progestogen-only pills, protection from ectopic pregnancy is not as good as with combined oral contraceptives. This has been associated with the frequent occurrence of ovulation during the use of progestogen-only pills. Despite the fact that NACREZ regularly inhibits ovulation, should the woman present amenorrhea or abdominal pain, the differential diagnosis should be taken into account in the differential diagnosis. possibility of an ectopic pregnancy.
Occasionally chloasma may occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking NACREZ.
The following conditions have been reported both during pregnancy and while taking sex steroids, but no association with progestogen use has been established:
- jaundice and / or cholestatic itching;
- formation of gallstones; porphyria;
- systemic lupus erythematosus;
- uraemic-haemolytic syndrome;
- Sydenham's chorea;
- herpes gestationis;
- hearing loss from otosclerosis;
- angioedema (hereditary).
Patients with rare hereditary diseases of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Maturation of the follicles
Follicular development occurs during the use of low-dose hormonal contraceptives. Follicles can sometimes grow larger than their normal size during the menstrual cycle. Enlarged follicles (functional cysts) generally disappear spontaneously. Often they are asymptomatic, but in some cases, mild abdominal pain may arise. Surgery is rarely needed.
04.5 Interactions with other medicinal products and other forms of interaction -
Interactions between hormonal contraceptives and other medicinal products can lead to intermenstrual bleeding and / or contraceptive failure. The following interactions have been reported in the literature (mainly with combined contraceptives but occasionally also with progestogen-only contraceptives).
Hepatic metabolism:
Interactions may occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones (such as hydantoins (e.g. phenytoin), barbiturates (e.g. phenobarbital), primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate , rifabutin, felbamate, ritonavir, nelfinavir, griseofulvin and products based on St. John's wort (Hypericum Perforatum)).
Maximal enzyme induction is not observed for 2-3 weeks but may then persist for at least 4 weeks after discontinuation of therapy. Women being treated with one of these medicinal products should temporarily use an additional barrier method in addition to NACREZ. With medicinal products that induce microsomal enzymes, the barrier method should be used during the time of concomitant drug administration and for 28 days after discontinuation. A non-hormonal method of contraception should be considered for women on long-term therapy with hepatic enzyme inducers.
During treatment with medicinal charcoal, the absorption of the steroid contained in the tablet may be reduced, thereby reducing the contraceptive efficacy. In these cases, the recommendation on forgotten tablets in section 4.2 applies.
Hormonal contraceptives can interfere with the metabolism of other active substances. Consequently, plasma and tissue concentrations may either increase (e.g. cyclosporins) or decrease.
Note: The prescribing information of concomitant medications should be consulted to identify possible interactions.
Laboratory analysis
Data obtained with COCs have shown that contraceptive steroids can affect the results of some laboratory tests, including biochemical parameters of liver, thyroid, renal and adrenal function, serum levels of (transporter) proteins, eg. corticosteroid-binding globulin and lipid / lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal range. It is not known to what extent this also applies to progestogen-only contraceptives.
04.6 Pregnancy and breastfeeding -
Pregnancy
NACREZ is not indicated during pregnancy. Should pregnancy occur during treatment with NACREZ, the drug should be discontinued.
Animal studies have shown that very high doses of progestogens can cause the masculinization of female fetuses.
Extensive epidemiological studies have found neither an increased risk of birth defects in babies born to women who had taken COCs prior to pregnancy nor a teratogenic effect if the COC was inadvertently taken in early pregnancy. Pharmacovigilance data collected for several desogestrel-based COCs do not indicate an increased risk.
Feeding time
NACREZ does not affect the production or quality (concentration of protein, lactose or fat) of breast milk. However, small amounts of etonogestrel are excreted in breast milk. As a result, 0.01-0.05 mcg of etonogestrel per kg body weight per day may be ingested by the child (based on an assumed milk ingestion of 150 ml / kg / day).
Limited long-term follow-up data are available on infants whose mothers started using desogestrel from week 4 to 8 postpartum. These infants were breastfed for 7 months and followed up to age 1. 5 years (n = 32) or up to the age of 2.5 years (n = 14). Assessment of growth and physical and psychomotor development indicated no difference compared to breastfed infants whose mothers used one Copper IUD Based on available data, NACREZ can be used during breastfeeding. However, the development and growth of the breastfed infant whose mother uses NACREZ should be closely monitored.
04.7 Effects on ability to drive and use machines -
NACREZ has no or negligible influence on the ability to drive and use machines.
04.8 Undesirable effects -
The most commonly reported undesirable effect in clinical trials is irregular bleeding. Some bleeding irregularity has been reported in up to 50% of women using desogestrel. Because desogestrel, unlike other progestogen-only contraceptives , causes near 100% "inhibition of ovulation", irregular bleeding is a more common phenomenon than other progestogen-only pills. In 20-30% of women, bleeding may become more frequent, while in another 20 % may be less frequent or completely absent. The duration of vaginal bleeding may also be longer. After a couple of months of treatment, bleeding tends to be less frequent. Correct information, some recommendations and a bleeding diary can improve the "acceptability of the event" by the woman.
The other most commonly reported undesirable effects in clinical trials with desogestrel (> 2.5%) were acne, mood changes, breast pain, nausea and weight gain. Undesirable effects are shown in the table below.
All undesirable effects are listed by system organ class and frequency;
Common (≥1 / 100 e
Uncommon (≥1 / 1,000 and
Rare (> 1 / 10,000 e
Not known (frequency cannot be estimated from the available data).
Breast discharge may occur during use of desogestrel. In rare cases, ectopic pregnancies have been reported (see section 4.4).
Some (serious) side effects have been reported in women using (combined) oral contraceptives. They include venous thromboembolic disorders, arterial thromboembolic disorders, hormone-dependent tumors (e.g. liver tumors, breast cancer) and chloasma, some of which are discussed in more detail in section 4.4.
Reporting of side effects
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
There are no reports of serious effects following overdose. Symptoms that can occur in this case are nausea, vomiting and, in young women, slight vaginal bleeding. There is no antidote and any treatment should be symptomatic.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: hormonal contraceptives for systemic use.
ATC code: G03AC09.
NACREZ is a progestogen-only pill containing the progestogen desogestrel. Like other progestogen-only pills, NACREZ is best suited for use during breastfeeding and for women who are unable or unwilling to use estrogen. Unlike traditional progestogen-only pills, the contraceptive effect of NACREZ is achieved primarily through the inhibition of ovulation. Other effects include an increase in the viscosity of the cervical mucus.
In a study conducted for 2 cycles, in which a progesterone level higher than 16 nmol / L was used for 5 consecutive days to define ovulation, an "ovulation incidence of 1% (1/103) was found." with a 95% confidence interval of 0.02% -5.29% in the ITT group (woman error and method failure). Ovulation inhibition was achieved from the first cycle of use. In this study, when desogestrel treatment was stopped after 2 cycles (56 consecutive days), ovulation occurred on average after 17 days (range 7 - 30 days).
In a comparative efficacy study (which allowed a maximum period of 3 hours for the forgotten tablet), the ITT overall Pearl Index calculated for desogestrel was 0.4 (95% confidence interval of 0.09-1 , 20), compared to the value of 1.6 (95% confidence interval of 0.42-3.96), calculated for 30 mcg of levonorgestrel.
The Pearl index for NACREZ is comparable to that historically calculated for COCs in the general COC-using population.
Treatment with NACREZ reduces estradiol levels to values corresponding to the beginning of the follicular phase. No clinically relevant effects have been observed on carbohydrate metabolism, lipid metabolism and haemostasis.
Pediatric population
There are no data on efficacy and safety in adolescents below 18 years.
05.2 "Pharmacokinetic properties -
Absorption
After oral administration, desogestrel (DSG) is rapidly absorbed and converted to etonogestrel (ENG). In steady state conditions, peak serum levels are reached 1.8 hours after tablet intake and the absolute bioavailability of ENG is approximately 70%.
Distribution
ENG is 95.5-99% bound to serum proteins, mainly albumin and, to a lesser extent, to SHBG.
Biotransformation DSG is metabolised by hydroxylation and dehydrogenation to the active metabolite ENG. ENG is metabolised through sulfur and glucuro-conjugation.
Elimination
ENG is eliminated with a mean half-life of approximately 30 hours, with no difference between single and multiple administrations. Steady state plasma levels are reached after 4-5 days. Serum clearance after i.v. of ENG is about 10 l / h. The excretion of ENG and its metabolites in the form of free steroid or conjugation products occurs through urine and faeces (in the ratio 1.5: 1).
In breastfeeding women, ENG is excreted in breast milk with a milk / serum ratio of 0.37-0.55. Based on these data and an estimated milk ingestion of 150 ml / kg / day , 0.01-0.05 mcg of etonogestrel can be ingested by the newborn.
05.3 Preclinical safety data -
Toxicological studies did not reveal any effects other than those foreseeable on the basis of the hormonal properties of desogestrel.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Core of the tablet:
Lactose monohydrate
Cornstarch
Povidone
Stearic acid
All-rac-alpha-tocopherol
Anhydrous colloidal silica
Coating film:
Hypromellose
Macrogol 400
Talc
Titanium dioxide
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
36 months: for blisters packed with pouch.
30 months: for blisters packed without pouch.
06.4 Special precautions for storage -
Storage conditions with the bag:
This medicine does not require any special storage conditions.
Storage conditions without the bag:
Do not store above 30 ° C.
06.5 Nature of the immediate packaging and contents of the package -
PVC / aluminum blister containing 28 film-coated tablets.
Calendar packs of 1x28, 3x28 and 6x28 film-coated tablets.
"The blister can be packed in a sachet"
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milan
08.0 MARKETING AUTHORIZATION NUMBER -
041950015 - "75 mcg film-coated tablets" 1 X 28 tablets in PVC / AL blister with calendar
041950027 - "75 mcg film-coated tablets" 3 X 28 tablets in PVC / AL blister with calendar
041950039 - "75 mcg film-coated tablets" 6 X 28 tablets in PVC / AL blister with calendar
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
GU n.14 of 17/01/2013
10.0 DATE OF REVISION OF THE TEXT -
November 2016
