AMBELINA

Route of administration: oral use Posology How to take Ambelina Tablets must be taken at approximately the same time each day, with some liquid if needed. One tablet is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7-day tablet free interval, during which time a withdrawal bleed usually occurs.

The bleeding usually starts within 2 to 3 days after the last tablet and may not end before the next pack is started. How to start Ambelina • No preceding hormonal contraceptive use [in the past month]: Tablet-taking is started on day 1 of the woman’s natural cycle (the first day of menstrual bleeding).

Starting on day 2-day 5 is allowed, but in that case an additional nonhormonal contraceptive method (barrier method) should be used during the first 7 days of treatment. • Changing from another combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, transdermal patch): The use of Ambelina tablets is preferably started on the day after the last active tablet of the previous COC (or after removal of the ring or patch), but at the latest on the day following the usual tablet- free (ring-free, patch-free) break or the last placebo tablet of the previous hormonal contraceptive.

• Changing from a progestogen-only method (oral contraceptive with only progesterone, injection, implant) or progestogen-releasing intrauterine system (IUS) If the oral contraceptive with only progesterone was used previously, the change can take place on any day; the change from an implant or IUS must take place on the day of removal, and from an injectable contraceptive at the time when the next injection would be due.

In each case, the use of an additional nonhormonal contraceptive method (barrier method) is necessary during the first 7 days taking Ambelina. • Following first-trimester abortion Ambelina may be started immediately. In this case, no additional contraceptive method is required.

• Following childbirth or second-trimester abortion The use of the tablets is started 21 to 28 days after delivery or second-trimester abortion. When starting later, an additional non-hormonal contraceptive method (barrier method) should be used during the first 7 days of tablet-taking If intercourse has already taken place, pregnancy must be ruled out before starting the use of Ambelina, or the woman must wait until her first menstrual period.

6 Pregnancy and Lactation. Management of missed tablets If one tablet is missed, but remembered and taken within 12 hours of the usual time, then contraceptive protection is not reduced. The subsequent tablets should be taken at the usual time.

If the usual tablet-taking time is missed by more than 12 hours, full contraceptive protection is no longer assured. The following two basic rules apply when a tablet is missed: 1. Tablet-taking must never be discontinued for longer than 7 days.

2. Tablets must be taken regularly for a minimum of 7 days in order to effectively suppress the hypothalamic-pituitary-ovarian axis. Therefore, the following procedures should be followed in the event that tablets are missed: • Week 1 The last tablet missed should be taken as soon as possible, even if this means taking 2 tablets in one day.

The remaining tablets are then taken at the usual time. In addition, a nonhormonal contraceptive method such as a condom should be used for the next 7 days. If intercourse took place in the 7 days before missing the tablet, the possibility of a pregnancy must be considered.

The more tablets missed and the closer they are to the usual tablet-free interval, the higher the risk of pregnancy. • Week 2 The last tablet missed should be taken as soon as possible, even if this means taking 2 tablets at the same time.

The remaining tablets are then taken at the usual time. Provided that the user has taken the tablets correctly in the 7 days prior to the first missed tablet, it is not necessary to use additional contraceptive measures. However, if this is not the case or she has missed more than one tablet, the user should be advised to take additional contraceptive precautions for the next 7 days.

• Week 3 The risk of reduced reliability is imminent because of the forthcoming tablet-free interval. However, by adjusting the tablet-taking schedule, reduced contraceptive protection can still be prevented. Therefore, by adhering to one of the following two options, there is no need to take additional contraceptive precautions, provided that in the 7 days prior to the first missed tablet the user has taken all the tablets correctly.

If this is not the case, the user should be advised to follow the first of these two options and take additional precautions for the next 7 days: 1. The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time.

She then continues to take the tablets at the usual time. e. without a break between packs. The user is unlikely to have withdrawal bleeding until the end of the second pack but she may experience spotting or breakthrough bleeding on tablet-taking days.

2. It is also possible to stop taking tablets from the current pack. The woman must then have a tablet-free break of 7 days, including the days she missed tablets, and then continue with the next pack. If the user misses several tablets and subsequently has no withdrawal bleeding in the first normal tablet-free interval, the possibility of pregnancy should be considered.

Advice in case of gastrointestinal disorders In case of severe gastrointestinal disorders (vomiting or diarrhea), absorption of the active ingredients may not be complete and additional contraceptive measures should be taken. If vomiting or severe diarrhea occurs within 3 to 4 hours after taking a tablet, a new tablet should be taken as soon as possible.

The new tablet should be taken within 12 hours of the usual […]

The following undesirable effects have been observed with use of combined oral contraceptives containing ethinylestradiol/levonorgestrel: Adverse events reported in clinical trialsOrgan system Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to <1/100) Rare (≥1/10,000 to < 1/1,000) Unknown Eye disorders Contact lens intolerance Gastrointestinal disorders Nausea abdominal pain Vomiting Diarrhea Immune system disorders Hypersensitivity Exacerbation of symptoms of hereditary and acquired angioedema.

4. 4: Tumors • The frequency of diagnosis of breast cancer is very slightly increased among OC users. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer.

Causation with COC use is unknown. 4. • Liver tumors (benign and malignant) Other conditions • Increased risk of pancreatitis in women with hypertriglyceridemia • Hypertension • Occurrence or deterioration of conditions for which association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis- related hearing loss • Liver function disturbances • Changes in glucose tolerance or effect on peripheral insulin resistance • Crohn’s disease, ulcerative colitis.

5). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Warnings If any of the conditions or risk factors mentioned below is present, the suitability of Ambelina should be discussed with the woman. In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman should be advised to contact her doctor to determine whether the use of Ambelina should be discontinued.

Risk of venous thromboembolism (VTE) The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, such as Ambelina, norgestimate or norethisterone are associated with the lowest risk of VTE.

The decision to use Ambelina should be taken after a discussion with the woman to ensure she understands the risk of VTE with Ambelina, how her current risk factors influence this risk, and that her VTE risk is highest in the first ever year of use.

There is also some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more. In women who do not use a CHC and are not pregnant, about 2 out of 10,000 will develop a VTE over the period of one year.

However, in any individual woman the risk may be far higher, depending on her underlying risk factors (see below). It is estimated that out of 10,000 women who use a CHC that contains levonorgestrel, about 61 will develop a VTE in a year.

This number of VTEs per year is fewer than the number expected in women during pregnancy or in the postpartum period. VTE may be fatal in 1-2% of cases. g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries. Risk factors for VTE The risk for venous thromboembolic complications in CHC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see table).

3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors – in this case her total risk of VTE should be considered. 3).

Table:

Risk factors for VTE Risk factor Comment Obesity (body mass index over 30 kg/m2) Risk increases substantially as BMI rises. Particularly important to consider if other risk factors also present. Prolonged immobilisation, major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma Note: temporary immobilisation including air travel >4 hours can also be a risk factor for VTE, particularly in women with other risk factors.

In these situations, it is advisable to discontinue use of the pill (in the case of elective surgery at least four weeks in advance) and not resume until two weeks after complete remobilisation. Another method of contraception should be used to avoid unintentional pregnancy.

Antithrombotic treatment should be considered if Ambelina has not been discontinued in advance. g. before 50). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use.

Other medical conditions associated with VTE Cancer, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease. Increasing age Particularly above 35 years.

There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the onset or progression of venous thrombosis. 6). Symptoms of VTE (deep vein thrombosis and pulmonary embolism) In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that she is taking a CHC.

Symptoms of deep vein thrombosis (DVT) can include: - unilateral swelling of the leg and/or foot or along a vein in the leg; - pain or tenderness in the leg which may be felt only when standing or walking, - increased warmth in the affected leg; red or discoloured skin on the leg.

g. g. respiratory tract infections). Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity. If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision.

Sometimes loss of vision can occur almost immediately. g. transient ischaemic attack, stroke). Arterial thromboembolic events may be fatal. Risk factors for ATE The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users increases in women with risk factors (see table).

Ambelina is contraindicated if a woman has one serious or […]

Combined hormonal contraceptives (CHCs) should not be used in the following conditions. If any of the conditions appear for the first time during CHC use, the product should be stopped immediately. g. g. g. g. g. 1. 5).