Damsel

Patient Information Leaflet

Damsel film-coated tablets

Estradiol valerate/Dienogest
Generic medicine
Please read all of this leaflet carefully before you start taking this medicine, as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Important things to know about combined hormonal contraceptives (CHCs):

• They are one of the most reliable reversible methods of contraception when used correctly;
• They slightly increase the risk of developing blood clots in veins and arteries, especially during the first year of use or when restarting a combined hormonal contraceptive after a break of 4 or more weeks;
• Be alert and contact your doctor if you think you have symptoms of a blood clot (see section 2 “Blood clots”).

Contents of this leaflet:

1. What Damsel is and what it is used for
2. What you need to know before taking Damsel
3. How to take Damsel
4. Possible side effects
5. How to store Damsel
6. Contents of the pack and other information

1. What Damsel is and what it is used for

• Damsel is a contraceptive pill and is used to prevent pregnancy.
• Each active coloured tablet contains a small amount of female hormones, estradiol valerate or estradiol valerate combined with dienogest.
• The 2 white tablets do not contain any active substance and are called inactive tablets.
• Contraceptive pills containing two hormones are called "combined pills".

2. What you need to know before taking Damsel

General information
Before starting to use Damsel, you must read the information about blood clots in section 2.
It is particularly important that you read about the symptoms of a blood clot – see section 2
"Blood clots".
Before taking Damsel, your doctor will ask you some questions about your personal
medical history and that of your family members. Your doctor will also measure your
blood pressure and, depending on your individual situation, may carry out additional tests.
This patient leaflet describes various situations in which you must stop using
Damsel or in which the reliability of Damsel may be reduced. In such situations, you must not have
sexual intercourse or must use additional non-hormonal contraceptive measures, such as
using a condom or another barrier method. Do not use the rhythm method or the basal body temperature method. These methods may be unreliable, as Damsel alters the monthly fluctuations in body temperature and cervical mucus.
Damsel, like all hormonal contraceptives, does not protect against HIV (AIDS) or other sexually transmitted infections.

When not to take Damsel
Do not use Damsel if you have any of the conditions listed below. If you have any of the
conditions listed below, consult your doctor. Your doctor will discuss with you other birth control methods that might be more suitable.
Do not take Damsel:

• if you have (or have ever had) a blood clot in a blood vessel of the leg (deep vein thrombosis, DVT), lung (pulmonary embolism, PE), or other organs;
• if you know you have a blood clotting disorder, such as protein C deficiency, protein S deficiency, antithrombin-III deficiency, factor V Leiden, or antiphospholipid antibodies;
• if you are about to undergo surgery or if you will be bedridden for a prolonged period (see section “Blood clots”);
• if you have ever had a heart attack or stroke;
• if you have (or have ever had) angina pectoris (a condition causing severe chest pain that may be an early sign of a heart attack) or a transient ischaemic attack (TIA – temporary stroke-like symptoms);
• if you have any of the following diseases, which may increase the risk of developing clots in the arteries:
  • severe diabetes with blood vessel damage
  • very high blood pressure
  • very high levels of fats (cholesterol or triglycerides) in the blood
  • a condition known as hyperhomocysteinaemia;
• if you have (or have ever had) a type of migraine called “migraine with aura”;
• if you have (or have ever had) a liver disease and your liver function is still abnormal;
• if you have (or have ever had) a liver tumour;
• if you have (or have ever had) cancer or suspect you may have cancer of the breast or genital organs;
• if you have unexplained vaginal bleeding;
• if you are allergic (hypersensitive) to estradiol valerate or dienogest or to any of the excipients of this medicine (listed in section 6). This may cause itching, rash, or swelling.

Warnings and precautions
When should you contact a doctor?
Seek urgent medical advice

• if you notice signs that may indicate a blood clot, which could mean you have a blood clot in the leg (deep vein thrombosis), in the
  lung (pulmonary embolism), a heart attack, or a stroke (see the following section “Blood clots”).
  For a description of the symptoms of these serious side effects, refer to the section “How to recognize a blood clot”.

Inform your doctor if any of the following conditions apply to you.
In certain situations, you need to be especially careful when using Damsel or any other combined oral contraceptive, and your doctor may need to examine you regularly. If any of these conditions appear or worsen while you are using Damsel, inform your doctor:

• if a close relative has or has had breast cancer;
• if you have a liver or gallbladder disease;
• if you have jaundice;
• if you have diabetes;
• if you suffer from depression;
• if you have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease);
• if you have systemic lupus erythematosus (SLE – a disease affecting the body’s natural defense system);
• if you have haemolytic uraemic syndrome (HUS – a blood clotting disorder causing kidney failure);
• if you have sickle cell anaemia (an inherited red blood cell disorder);
• if you have high levels of fats in the blood (hypertriglyceridaemia) or a family history of this condition. Hypertriglyceridaemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas);
• if you are about to undergo surgery or if you will be bedridden for a prolonged period (see section 2 “Blood clots”);
• if you have recently given birth, your risk of developing blood clots is higher. Ask your doctor how long after childbirth you can start taking Damsel;
• if you have inflammation of veins near the skin surface (superficial thrombophlebitis);
• if you have varicose veins;
• if you have epilepsy (see section “Other medicines and Damsel”);
• if you have a condition that first appeared during pregnancy or during previous use of sex hormones, for example, hearing loss, porphyria (a blood disorder), herpes gestationis (blistering rash during pregnancy), Sydenham’s chorea (a nerve disorder causing sudden body movements);
• if you have (or have had) patchy yellow-brown skin discoloration, known as “chloasma”, especially on the face (melasma). In this case, avoid direct exposure to sunlight or ultraviolet rays;
• if you have hereditary or acquired angioedema. Stop taking Damsel and consult your doctor immediately if you experience symptoms such as swelling of the face, tongue and/or throat and/or difficulty swallowing or hives with breathing difficulties, which are indicative of angioedema. Medicines containing oestrogens may induce or worsen angioedema symptoms;
• if you have heart or kidney failure.

Consult your doctor before taking Damsel.
Additional information for specific patient groups
Use in children:
Damsel is not indicated for use in women who have not yet had their first menstrual period.
BLOOD CLOTS
Using a combined hormonal contraceptive such as Damsel increases the risk of developing
a blood clot compared to not using one. In rare cases, a blood clot can block blood vessels and cause serious problems.
Blood clots can develop

• in veins (a condition called “venous thrombosis”, “venous thromboembolism” or VTE);
• in arteries (a condition called “arterial thrombosis”, “arterial thromboembolism” or ATE).

Recovery from blood clots is not always complete. Rarely, serious long-term effects may occur, or very rarely, these effects may be fatal.
It is important to remember that the overall risk of a dangerous blood clot associated with Damsel is low.
HOW TO RECOGNIZE A BLOOD CLOT
Seek immediate medical advice if you notice any of the following signs or symptoms.
Do you have any of these signs? What might you be suffering from?

• swelling in one leg or along a vein in the leg or foot, Deep vein thrombosis especially if accompanied by: o pain or tenderness in the leg, which may only be felt when standing or walking; o increased warmth in the affected leg; o change in skin colour of the leg, such as paleness, redness, or blueness.
• sudden and unexplained shortness of breath or rapid breathing; Pulmonary embolism
• sudden cough without an obvious cause, possibly with coughing up of blood;
• sharp chest pain that may worsen when breathing deeply;
• severe dizziness or lightheadedness;
• rapid or irregular heartbeat;
• severe stomach pain.

If you are unsure, inform your doctor, as some of these symptoms
such as cough or shortness of breath may be mistaken for a milder condition such as a respiratory tract infection (e.g. a “common cold”).
Symptoms occurring more frequently in an eye: Retinal vein thrombosis

• sudden loss of vision or (blood clot in the eye)
• painless blurring of vision that may progress to loss of vision.
• pain, discomfort, pressure, or heaviness in the chest; Heart attack
• squeezing or fullness sensation in the chest, in one arm, or under the sternum;
• feeling of fullness, indigestion, or choking;
• discomfort in the upper body spreading to the back, jaw, throat, arms, and stomach;
• sweating, nausea, vomiting, or dizziness;
• extreme weakness, anxiety, or shortness of breath;

BLOOD CLOTS IN A VEIN
What can happen if a blood clot forms in a vein?

• The use of combined hormonal contraceptives has been associated with an increased risk of developing blood clots in the veins (venous thrombosis). However, these side effects are rare. In most cases, they occur during the first year of using a combined hormonal contraceptive.
• If a blood clot forms in a vein of the leg or foot, it can cause deep vein thrombosis (DVT).
• If a blood clot travels from the leg and lodges in the lung, it can cause a pulmonary embolism.
• Very rarely, the clot may form in another organ such as the eye (retinal vein thrombosis).

When is the risk of developing a blood clot in a vein highest?
The risk of developing a blood clot in a vein is highest during the first year in which you
first start taking a combined hormonal contraceptive. The risk may also be higher
if you restart taking a combined hormonal contraceptive (the same medication or a different one)
after a break of 4 or more weeks.
After the first year, the risk decreases but remains slightly higher than in women who do not use a
combined hormonal contraceptive.
When you stop taking Damsel, the risk of developing a blood clot returns to normal levels within a few weeks.

What is the risk of developing a blood clot?
The risk depends on your natural risk of VTE and on the type of combined hormonal contraceptive you are taking.
The overall risk of developing a blood clot in the leg or lung (DVT or PE) with Damsel is low.

• Among 10,000 women who do not use any combined hormonal contraceptive and who are not pregnant, about 2 will develop a blood clot in one year.
• Among 10,000 women who use a combined hormonal contraceptive containing levonorgestrel, norethisterone, or norgestimate, about 5–7 will develop a blood clot in one year.
• The risk of developing a blood clot with Damsel is approximately the same as with other combined hormonal contraceptives, including contraceptives containing levonorgestrel.
• The likelihood of developing a blood clot depends on your medical history (see below “Factors that increase the risk of developing a blood clot”).

Factors that increase the risk of developing a blood clot in a vein
The risk of developing a blood clot with Damsel is low, but certain conditions can increase it. Your risk is higher:

• if you are very overweight (body mass index or BMI above 30 kg/m²);
• if a close relative has had a blood clot in a leg, lung, or another organ at a young age (e.g., under approximately 50 years). In this case, you might have an inherited blood clotting disorder;
• if you are scheduled for surgery or need to remain bedridden due to injury or illness, or if you have a leg in plaster. You may need to stop taking Damsel several weeks before surgery or during periods of reduced mobility. If you need to stop taking Damsel, ask your doctor when you can start taking it again;
• as you get older (especially over 35 years);
• if you gave birth less than a few weeks ago.

The risk of developing a blood clot increases when you have more than one of these conditions.
Air travel (lasting >4 hours) may temporarily increase the risk of blood clot formation, especially if you have other listed risk factors.
It is important that you inform your doctor if any of these conditions apply to you, even if you are unsure. Your doctor may decide to have you stop taking Damsel.
If any of the above conditions change while you are using Damsel, for example, if a close relative develops thrombosis without a known cause or if you gain significant weight, contact your doctor.

BLOOD CLOTS IN AN ARTERY
What can happen if a blood clot forms in an artery?
Like blood clots in a vein, clots in an artery can cause serious problems—for example, they can lead to a heart attack or stroke.

Factors that increase the risk of developing a blood clot in an artery
It is important to note that the risk of heart attack or stroke associated with the use of Damsel is very low, but it may increase:

• with increasing age (over 35 years);
• if you smoke. When using a combined hormonal contraceptive such as Damsel, it is advisable to stop smoking. If you cannot stop smoking and are over 35 years old, your doctor may recommend using a different type of contraceptive;
• if you are overweight;
• if you have high blood pressure;
• if a close relative had a heart attack or stroke at a young age (under approximately 50 years). In this case, you may also have an increased risk of heart attack or stroke;
• if you or a close relative have high levels of fats in the blood (cholesterol or triglycerides);
• if you suffer from migraine, especially migraine with aura;
• if you have heart problems (valvular defect, a heart rhythm disorder called atrial fibrillation);
• if you have diabetes.

If you have more than one of these conditions or if one is particularly severe, the risk of developing a blood clot may be even higher.
If any of the above conditions change while you are using Damsel—for example, if you start smoking, if a close relative develops thrombosis without a known cause, or if you gain significant weight—contact your doctor.

Damsel and cancer
Breast cancer has been observed slightly more frequently in women using combined oral contraceptives, but it is not known whether this is due to the treatment. For example, more tumours may be detected in women using combined oral contraceptives because they are examined more frequently. The risk of breast cancer gradually decreases after stopping combined hormonal contraception. It is important that you regularly check your breasts and contact your doctor if you feel any lump.
In rare cases, benign liver tumours have been observed in women using oral contraceptives, and even more rarely malignant liver tumours. In isolated cases, these tumours have led to life-threatening internal bleeding. Contact your doctor if you experience severe abdominal pain.
Some studies suggest that long-term use of the pill may increase the risk of developing cervical cancer. However, it is unclear to what extent sexual behaviour or other factors such as human papillomavirus (HPV) contribute to this risk.

Psychiatric disorders
Some women using hormonal contraceptives, including Estradiol valerate/Dienogest, have reported depression or depressed mood. Depression can be severe and may sometimes lead to suicidal thoughts. If you experience mood changes or depressive symptoms, consult your doctor as soon as possible for further medical advice.

Intermenstrual bleeding
During the first few months of taking Damsel, unexpected bleeding may occur. Usually, bleeding starts on day 26, the day you take the second brown tablet, or in the following days. Data from diaries kept by women during a clinical study with Estradiol valerate/Dienogest show that unexpected bleeding in a given cycle is not uncommon (observed in 10–18% of users). If unexpected bleeding occurs for more than three consecutive months, or if it appears after several months, your doctor should investigate the cause.

What to do if menstruation does not occur on day 26 or in the following days
Data from diaries kept by women during a clinical study with Estradiol valerate/Dienogest show that it is not uncommon for menstruation not to occur on day 26 (observed in approximately 15% of cycles).
If you have taken all tablets correctly, have not vomited or had severe diarrhoea, and have not taken other medications, it is highly unlikely that you are pregnant.
If you miss two consecutive periods, or if you have not taken the tablets correctly, you may be pregnant. Contact your doctor immediately. Do not start the next pack until pregnancy has been ruled out.

Other medicines and Damsel
Always inform your doctor about any medicines or herbal products you are currently taking. Also inform any other doctor or dentist who prescribes you medicines (or the pharmacist from whom you obtained the medicine) that you are taking Damsel. They can advise you whether you need to use additional contraceptive measures (e.g., condoms) and, if so, for how long.
Some medicines:

• may affect Damsel levels in the blood;
• may make it less effective in preventing pregnancy;
• may cause unexpected bleeding.

These include medicines used to treat:

• epilepsy (e.g., primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate);
• tuberculosis (e.g., rifampicin);
• HIV infection and hepatitis C virus (ritonavir, nevirapine, efavirenz, known as protease inhibitors and non-nucleoside reverse transcriptase inhibitors);
• hepatitis C virus (HCV) (such as combination regimens ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin; glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir) (see section 4.4). These may cause increases in liver function test results (increase in liver enzyme ALT) in women using COCs containing ethinylestradiol. Damsel contains estradiol instead of ethinylestradiol. It is not known whether an increase in liver ALT enzyme may occur when using Damsel with this HCV combination regimen. Your doctor will provide you with necessary instructions;
• fungal infections (e.g., griseofulvin, ketoconazole); or the herbal preparation St. John’s wort.

Damsel may affect the effect of other medicines, for example:

• medicines containing cyclosporine;
• the antiepileptic lamotrigine (this may cause an increase in the frequency of epileptic seizures).

Ask your doctor or pharmacist for advice before taking any medicine. Your doctor or pharmacist can advise you whether you need to take additional protective measures while taking Damsel with other medicines.

Damsel with food
Damsel can be taken with or without food.

Laboratory tests
If you need a blood test or other laboratory tests, inform your doctor or laboratory staff that you are taking the pill, as oral contraceptives may influence the results of certain tests.

Pregnancy and breastfeeding
During pregnancy, you must not use Damsel. If you become pregnant while taking Damsel, stop treatment immediately and contact your doctor. If you wish to become pregnant, you may stop taking Damsel at any time (see also "If you stop taking Damsel").

Generally, you should not take Damsel during breastfeeding. If you wish to take the pill while breastfeeding, you should consult your doctor.

Ask your doctor or pharmacist for advice before taking any medicine during pregnancy or breastfeeding.

Driving and using machines
There are no reasons to believe that Damsel affects the ability to drive or use machinery.

Damsel contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking Damsel.

3. How to take Damsel

Each blister contains 26 coloured active tablets and 2 white inactive tablets.
Take one Damsel tablet every day. You may take the tablets with or without food, but you must take them at approximately the same time each day.

Preparing the pack
To help you follow the correct sequence, there are 7 self-adhesive labels with the 7 days of the week. Choose the adhesive label starting with the day on which you begin taking the tablets. For example, if you start on Wednesday, use the label starting with "WED". Attach the adhesive label along the top of the blister so that the first day is above the tablet marked "1".
This way, each tablet will have a day indicated above it, allowing you to check whether you have taken the pill on any given day. Follow the direction of the arrow on the blister until you have taken all 28 tablets.

Usually, the so-called withdrawal bleeding starts while you are taking the second brown tablet or the white tablets, and it may not have finished before you start the next blister. Some women may still be bleeding even after they have already started taking the first tablets of the new blister.

Start the next blister without a break, i.e. the day after finishing the current blister, even if bleeding has not yet stopped.

If you use Damsel in this way, contraceptive protection is maintained throughout the 2 days during which you are taking the inactive tablets.

When to start the first blister

• If you have not used any hormonal contraceptive in the previous month: Start taking Damsel on the first day of your cycle (the first day of menstruation).
• Switching from another combined hormonal contraceptive pill, or from a combined vaginal contraceptive ring, or contraceptive patch: Start taking Damsel the day after the last active tablet (the last tablet containing active ingredients) of the previous pill. When switching from a vaginal ring or a patch, start using Damsel on the day of removal, or follow your doctor's advice.
• Switching from a progestogen-only method (progestogen-only pill, injection, implant, or progestogen-releasing IUS, intrauterine system): You may switch at any time from the progestogen-only pill (or from an implant or IUS on the day of its removal, or from an injectable when the next injection would have been due), but in all these cases you must use additional contraceptive measures (e.g. condom) for the first 9 days of using Damsel.
• After an abortion: Follow your doctor's advice.
• After childbirth: You may start taking Damsel between the 21st and 28th day after delivery. If you start later than the 28th day, use a barrier method (e.g. condom) during the first 9 days of taking Damsel. If you have had sexual intercourse after childbirth before starting Damsel, you must either exclude pregnancy or wait for the next menstrual period. If you wish to start taking Damsel after pregnancy and are breastfeeding, read the section “Pregnancy and breastfeeding”. Consult your doctor if you are unsure about when to start.

If you take more Damsel than you should
There have been no reports of serious harmful effects from taking too many Damsel tablets.
If several tablets are taken at once, you may experience nausea or vomiting. Young girls may experience vaginal bleeding.
If you have taken too many Damsel tablets, or if you find that a child has taken any of the tablets, contact your doctor or pharmacist immediately.

If you forget to take Damsel

Inactive tablets: If you forget one white tablet (the two tablets at the end of the blister), you do not need to take it later, as they contain no active ingredients. However, it is important that you discard the forgotten white tablet(s) so that the number of days taking inactive tablets does not increase; doing so would increase the risk of pregnancy. Continue taking the next tablet at your usual time.

Active tablets: Depending on the day of the cycle when one active tablet has been forgotten, you must use additional contraceptive measures, such as a barrier method (e.g. condom).
Take the tablets according to the instructions below. For details, also see the "Missed pill chart".

• If the delay in taking a tablet is less than 12 hours, contraceptive protection is not reduced. Take the tablet as soon as you remember, then continue taking the following tablets at your usual time.
• If the delay in taking a tablet is more than 12 hours, contraceptive protection may be reduced. Depending on the day of the cycle when the tablet was missed, you must use additional contraceptive measures, such as a barrier method (e.g. condom). For details, also see the "Missed pill chart".
• More than one tablet missed in a blister: Consult your doctor.

Do not take more than 2 active tablets in one day.
If you forgot to start a new blister, or if you missed one or more tablets during days 3–9 of the blister, there is a risk of pregnancy (if you had sexual intercourse in the 7 days before forgetting the tablet). In this case, consult your doctor. The greater the number of tablets missed (especially those during days 3–24) and the closer the missed tablets are to the inactive tablet phase, the higher the risk that contraceptive protection is reduced. For details, see also the "Missed tablet chart".
If you have missed any of the active tablets in a blister and do not have a withdrawal bleed at the end of the blister, you may be pregnant. Consult your doctor before starting the next blister.

Use in children
No data are available in adolescents under 18 years of age.

What to do if you vomit or have severe diarrhoea
If you vomit within 3–4 hours of taking an active tablet, or if you have severe diarrhoea, the active ingredients of the tablet may not be completely absorbed by your body.
This situation is similar to that which occurs when you forget to take a tablet. After vomiting or severe diarrhoea, you should take the next tablet as soon as possible, ideally within 12 hours of your usual pill-taking time. If this is not possible, or if more than 12 hours have passed, follow the instructions under “If you forget to take Damsel”. If you do not wish to change your normal dosing schedule, take the corresponding tablet from another blister.

If you stop taking Damsel
You may stop taking Damsel at any time. If you still wish to avoid pregnancy, consult your doctor for advice on other reliable contraceptive methods. If you wish to become pregnant, stop taking Damsel and wait for one menstrual cycle before trying to conceive. This will allow you to calculate the expected date of delivery more accurately.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Damsel can cause side effects, although not everybody will experience them. If you experience any side effect, especially if it is severe or persistent, or if you notice any change in your health that you think could be due to Damsel, inform your doctor.

An increased risk of developing blood clots in the veins (venous thromboembolism (VTE)) or blood clots in the arteries (arterial thromboembolism (ATE)) exists in all women taking combined hormonal contraceptives. For more detailed information on the different risks associated with taking combined hormonal contraceptives, see section 2 “What you should know before using Damsel”.

Serious side effects

Serious reactions associated with the use of the pill, along with related symptoms, are described in the following sections: “Blood clots” and “Damsel and cancer”. Please read these sections carefully and consult your doctor immediately if necessary.

Other possible side effects

The following side effects have been reported with the use of Damsel:

Common side effects (may affect between 1 and 10 users in 100)

• Headache
• Abdominal pain, nausea
• Acne
• Absence of menstruation, breast tenderness, painful menstruation, irregular menstruation (with heavy irregular bleeding)
• Weight gain

Uncommon side effects (may affect between 1 and 10 users in 1,000)

• Fungal infection, fungal infection of the vulva and vagina, vaginal infection
• Increased appetite
• Depression, depressed mood, emotional disorder, difficulty sleeping, decreased sexual desire, mental disorder, mood swings
• Dizziness, migraine
• Hot flushes, high blood pressure
• Diarrhea, vomiting
• Increased liver enzymes
• Hair loss, excessive sweating (hyperhidrosis), itching, rash
• Muscle cramps
• Breast enlargement, breast lumps, abnormal cell growth in the cervix (cervical dysplasia), genital dysfunctional bleeding, pain during intercourse, fibrocystic mastopathy, heavy menstruation, menstrual disorders, ovarian cyst, pelvic pain, premenstrual syndrome, benign uterine tumour, uterine contractions, vaginal/uterine bleeding including spotting, vaginal discharge, vulvovaginal dryness
• Fatigue, irritability, swelling of certain parts of the body, for example the ankles (edema)
• Weight loss, changes in blood pressure

Rare side effects (may affect between 1 and 10 users in 10,000)

• Candida infection, oral herpes, pelvic inflammatory disease, an eye vascular condition resembling a fungal infection (presumed ocular histoplasmosis syndrome), a fungal skin infection (tinea versicolor), urinary tract infection, bacterial inflammation of the vagina
• Fluid retention, increase in certain blood fats (triglycerides)
• Aggressiveness, anxiety, feeling of unhappiness, increased sexual desire, nervousness, nightmares, restlessness, sleep disturbances, stress
• Reduced attention, sensation of “pins and needles”, vertigo
• Intolerance to contact lenses, dry eyes, swollen eyes
• Heart attack (myocardial infarction), palpitations
• Bleeding from a varicose vein, low blood pressure, inflammation of superficial veins, vein pain
• Dangerous blood clots in a vein or an artery, for example: in a leg or foot (DVT) or in a lung (PE) or heart attack or stroke or mini-stroke or transient symptoms similar to stroke, known as transient ischaemic attack (TIA), or blood clots in the liver, stomach/intestine, kidneys or eye. The likelihood of developing a blood clot may be higher if you have any other condition that increases this risk (see section 2 for more information on conditions that increase the risk of blood clots and symptoms of a blood clot).
• Constipation, dry mouth, indigestion, heartburn
• Liver nodules (focal nodular hyperplasia), chronic inflammation of the gallbladder
• Skin allergic reactions, yellow-brown spots (chloasma) and other pigmentary disorders, growth of hair in a male pattern, excessive hair growth, skin disorders such as: dermatitis and neurodermatitis, dandruff and oily skin (seborrhoea) and other skin disorders
• Back pain, jaw pain, feeling of heaviness
• Urinary tract pain
• Abnormal bleeding after discontinuation, benign breast nodules, early-stage breast cancer, breast cysts, breast discharge, cervical polyp, cervical redness, bleeding during intercourse, spontaneous milk secretion from the breast, genital discharge, scanty menstruation, delayed menstruation, rupture of ovarian cyst, foul-smelling vaginal discharge, burning sensation in the vulva and vagina, vulvovaginal discomfort
• Swollen lymph nodes
• Asthma, breathing difficulty, nosebleed
• Chest pain, tiredness and general feeling of malaise, fever
• Abnormal Pap test (cervical smear)

Additional information (taken from diaries kept by women during a clinical study with estradiol valerate/dienogest) on the possible side effects “irregular menstruation (heavy irregular bleeding)” and “absence of menstruation” is provided in the sections “Intermenstrual bleeding” and “What to do if menstruation does not occur on day 26 or subsequent days”.

Description of selected adverse reactions

Adverse reactions with very low frequency or delayed onset, considered to be related to those of combined oral contraceptives, may also occur during the use of Damsel and are listed below (see also sections “When not to take Damsel” and “Warnings and precautions”):

• Liver tumours (benign or malignant)
• Erythema nodosum (soft red subcutaneous nodules), erythema multiforme (skin rash with red spots or lesions)
• Hypersensitivity (including symptoms such as rash, urticaria)
• In women with hereditary angioedema (characterized by sudden swelling, for example of the eyes, mouth, throat, etc.), the oestrogens contained in combined oral contraceptive pills may trigger or worsen symptoms of angioedema.

If liver function is impaired, temporary discontinuation of combined oral contraceptive pills may be necessary.

Reporting of side effects:

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Damsel

Keep this medicine out of the sight and reach of children.
This medicine requires no special storage conditions.
Do not use this medicine after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Damsel contains
The active substances are estradiol valerate, or estradiol valerate combined with dienogest.
Each blister (28 film-coated tablets) of Damsel contains 26 active tablets in 4 different colours
in rows 1, 2, 3 and 4, as well as 2 inactive white tablets in row 4.
Composition of the coloured tablets containing one or two active substances:

• 2 dark yellow tablets, each containing 3 mg of estradiol valerate
• 5 pink tablets, each containing 2 mg of estradiol valerate and 2 mg of dienogest
• 17 light yellow tablets, each containing 2 mg of estradiol valerate and 3 mg of dienogest
• 2 brown tablets, each containing 1 mg of estradiol valerate

Composition of the inactive white tablets:
These tablets do not contain any active substance.

Other excipients in the coloured active tablets are:
Tablet core: monohydrate lactose, maize starch, pregelatinized maize starch, povidone (E1201), anhydrous colloidal silica, magnesium stearate (E572).
Tablet coating: hypromellose (E464), macrogol 6000, iron oxide red (E172), titanium dioxide (E171), talc (E553b), iron oxide yellow (E172).

Excipients in the inactive white tablets are:
Tablet core: monohydrate lactose, microcrystalline cellulose, magnesium stearate (E572).
Tablet coating: partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc (E553b).

Description of the appearance of Damsel and contents of the pack
Damsel tablets are film-coated tablets; the tablet core is covered with a coating.
Each blister (28 film-coated tablets) contains 2 dark yellow tablets in row 1, 5 pink tablets in row 1, 17 light yellow tablets in rows 2, 3 and 4, 2 brown tablets in row 4, and 2 inactive white tablets in row 4.
The dark yellow active tablet is a round, biconvex, film-coated tablet, marked with "L" on one side.
The pink active tablet is a round, biconvex, film-coated tablet, marked with "L" on one side.
The light yellow active tablet is a round, biconvex, film-coated tablet, marked with "L" on one side.
The brown active tablet is a round, biconvex, film-coated tablet, marked with "L" on one side.
The inactive white tablet is a round, biconvex, film-coated tablet, marked with "PL" on one side.

Damsel is available in packs of 1, 3 or 6 blisters, each containing 28 tablets.
A cardboard carton for storage of the blister is included.
Not all pack sizes may be marketed.

Marketing Authorization Holder
S.F. GROUP S.r.l.
Via Tiburtina, 1143
00156 Rome, Italy

Manufacturers
Cyndea Pharma S.L.
Avenida Agreda 31
Polígono Industrial Emiliano Revilla Sanz
Ólvega, Soria
42110 Spain

This medicinal product is authorized in the European Economic Area countries under the following names:
Sweden: Rubinia
Italy: Damsel