Novofem

PATIENT INFORMATION LEAFLET

Enclosed leaflet: information for the user

Novofem, coated tablets

estradiol + norethisterone acetate

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Novofem and what is it used for

Novofem is a medicine used in sequential combined hormone replacement therapy (HRT) administered daily without interruption to postmenopausal women, at least 6 months after their last natural menstrual period.
Novofem contains 2 female sex hormones - estrogen (estradiol) and progestogen (norethisterone acetate). The estradiol in Novofem is identical to the estradiol produced by the ovaries in women and is classified as a natural estrogen. Norethisterone acetate is a synthetic progestogen that acts similarly to progesterone - another important female sex hormone.
Novofem is used to:
relieve symptoms occurring after menopause
During menopause, the amount of estrogen produced by the woman's body decreases. This causes symptoms such as a feeling of heat on the face, neck, and chest ("hot flashes"). Novofem relieves these symptoms. Novofem should only be prescribed to a patient if the symptoms significantly interfere with daily life.
prevent osteoporosis
After menopause, some women develop brittle bones (osteoporosis). All available options should be discussed with your doctor.
If the patient is at increased risk of fractures due to osteoporosis and other medicines are not suitable, Novofem can be used to prevent osteoporosis after menopause.
Experience in treating women over 65 years of age is limited.

2. Important information before taking Novofem

Medical history and regular medical examinations

Taking HRT involves risks that should be considered when the patient decides whether to take hormone replacement therapy or continue it.
Experience in treating women in premature menopause (due to ovarian failure or surgical procedure) is limited. If the patient is experiencing premature menopause, the risk associated with HRT may differ. In this case, you should talk to your doctor.
Before starting (or resuming) HRT, the doctor will take a medical history, including a family history. The doctor may decide to perform tests, including a breast examination and (or) gynecological examination, if necessary.
If the patient decides to take Novofem, she should regularly attend medical examinations (at least once a year). During these examinations, she should discuss the benefits and risks of taking Novofem with her doctor.
The patient should regularly undergo mammography examinations, in accordance with the doctor's recommendations.

When not to take Novofem

In case of any of the following diseases or if in doubt, you should tell your doctorbefore taking Novofem.
Do not start taking Novofem if:

• breast cancer has been diagnosed, occurred in the past, or is suspected;
• endometrial cancer (endometrium cancer) or other estrogen-dependent tumors have been diagnosed, occurred in the past, or are suspected;
• there are unexplained bleeding from the genital tract;
• there is excessive growth of the endometrium (endometrial hyperplasia) and it is not being treated;
• blood clots in the veins (venous thromboembolic disease), such as deep vein thrombosis or pulmonary embolism, have been diagnosed or occurred in the past;
• there is a blood clotting disorder (a disorder with a tendency to form blood clots, such as protein C, protein S, or antithrombin deficiency);
• there are or have been diseases caused by blood clots in the arteries (thromboembolic disorders) such as heart attack, stroke, or angina pectoris;
• there is or has been liver disease, and liver function tests have not returned to normal;
• there is hypersensitivity and (or) allergy to estradiol, norethisterone acetate, or any of the other ingredients of Novofem (listed in section 6. "Contents of the pack and other information");
• there is a rare, hereditary blood disease porphyria.

If any of the above conditions occur for the first time while taking Novofem, you should stop taking the medicine and consult a doctor.

Warnings and precautions

Before starting treatment, you should inform your doctor about any current or past disorders, as they may recur or worsen while taking Novofem. In this case, your doctor may decide that you need close monitoring:

• uterine fibroids (uterine fibroids);
• endometriosis or excessive growth of the endometrium (endometrial hyperplasia) in the medical history;
• factors that increase the risk of blood clots;
• factors that increase the risk of estrogen-dependent tumors (such as breast cancer in the mother, sister, or grandmother);
• high blood pressure;
• liver disease, such as liver tumor (benign tumor);
• diabetes;
• gallstones;
• migraine or severe headaches;
• immune system disease affecting many organs (systemic lupus erythematosus);
• epilepsy;
• asthma;
• ear disease leading to gradual hearing loss (otosclerosis);
• high levels of fats (triglycerides) in the blood;
• fluid retention due to impaired heart or kidney function;
• a condition in which the thyroid gland does not produce enough thyroid hormones (hypothyroidism) and the patient is taking thyroid hormone replacement therapy;
• a hereditary condition that causes recurring episodes of swelling (hereditary angioedema) or a history of sudden swelling of the hands, face, feet, mouth, eyes, tongue, throat (airway obstruction) or gastrointestinal tract (acquired angioedema);
• lactose intolerance.

In case of the following diseases during HRT, it is recommended to stop taking Novofem immediately and consult a doctor:

• if any of the conditions listed in "When not to take Novofem" occur;
• if the skin or whites of the eyes turn yellow (jaundice), which may be a sign of liver function disorders;
• if there is swelling of the face, tongue, and (or) throat, and (or) difficulty swallowing or hives, accompanied by difficulty breathing, which indicate angioedema;
• if there is a significant increase in blood pressure (symptoms may include: headache, fatigue, and dizziness);
• if a migraine-type headache occurs for the first time;
• if pregnancy is detected;
• if there are symptoms of a blood clot, such as:
• painful swelling and redness of the legs,
• sudden chest pain,
• breathing difficulties. For more information, see "Blood clots in the veins (venous thromboembolic disease)".

Note:Novofem is not a contraceptive. If it has been less than 12 months since the last menstrual period or the patient is under 50 years of age, it may be necessary to use an additional method of contraception. You should talk to your doctor.

HRT and cancer

Excessive growth of the endometrium (endometrial hyperplasia) and endometrial cancer

Taking only estrogens in HRT increases the risk of excessive growth of the endometrium (endometrial hyperplasia) and endometrial cancer.
The progestogen in Novofem helps reduce this additional risk.
Comparison
In women aged 50-65 who do not take HRT and have a uterus, endometrial cancer is diagnosed in about 5 out of 1000 women.
In women aged 50-65 who take only estrogen HRT and have a uterus, the number of cases ranges from 10 to 60 per 1000 (i.e., 5 to 55 additional cases), depending on the duration of treatment and the dose of estrogen taken.

Unexpected bleeding

While taking Novofem, monthly bleeding (so-called withdrawal bleeding) will occur. However, if unexpected bleeding or spotting occurs between monthly bleeding, which:

• lasts longer than the first 6 months,
• occurs after taking Novofem for more than 6 months,
• continues despite stopping HRT, you should contact your doctor as soon as possible.

Breast cancer

Data confirm that taking hormone replacement therapy (HRT) in the form of a combination of estrogen and progestogen or only estrogen increases the risk of breast cancer. The additional risk depends on how long the patient takes HRT. This additional risk becomes apparent after 3 years of HRT. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT lasted more than 5 years.
Comparison
In the case of women aged 50-54 who do not take HRT, breast cancer will be diagnosed in about 13 to 17 out of 1000 women over a period of 5 years.
In the case of women aged 50 who start 5-year estrogen HRT, the number of cases will be 16-17 per 1000 patients (i.e., 0 to 3 additional cases).
In the case of women aged 50 who start 5-year estrogen-progestogen HRT, the number of cases will be 21 per 1000 patients (i.e., 4 to 8 additional cases).
In the case of women aged 50-59 who do not take HRT, breast cancer will be diagnosed in about 27 out of 1000 women over a period of 10 years.
In the case of women aged 50 who start 10-year estrogen HRT, the number of cases will be 34 per 1000 patients (i.e., 7 additional cases).
In the case of women aged 50 who start 10-year estrogen-progestogen HRT, the number of cases will be 48 per 1000 patients (i.e., 21 additional cases).

It is recommended to regularly examine the breasts. You should contact your doctor if you notice any of the following changes:

• retraction of the skin,
• changes in the nipple,
• presence of lumps that are visible or palpable.

In addition, it is recommended to perform screening mammography examinations in accordance with the doctor's recommendations. Before the examination, you should inform the nurse or medical staff performing the X-ray examination about taking hormone replacement therapy, as this medicine may increase breast density, which can affect the result of the mammography examination. Not all lumps can be detected during a mammography examination in areas with increased breast density.

Ovarian cancer

Ovarian cancer is rare - much rarer than breast cancer. Taking HRT that includes only estrogens or a combination of estrogens and progestogens is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer depends on age. For example, in women aged 50-54 who do not take HRT, ovarian cancer will be diagnosed over a period of 5 years in about 2 out of 2000 women.
In women who took HRT for 5 years, it will occur in about 3 out of 2000 women taking it (i.e., about 1 additional case).

Effect of HRT on the heart and circulation

Blood clots in the veins (venous thromboembolic disease)

The risk of blood clots in the veins is 1.3 to 3 times higher in women taking HRT compared to those not taking it, especially in the first year of treatment.
Blood clots can be life-threatening and if they move to the lungs, they can cause chest pain, shortness of breath, loss of consciousness, and even death.
The risk of blood clots in the veins is higher if the patient is older and if the following factors occur. You should inform your doctor if:

• the patient cannot walk for a long time due to serious surgery, injury, or illness (see also section 3. "If surgery is planned");
• there is obesity (body mass index - BMI > 30 kg/m2);
• there have been thromboembolic disorders in the past that required taking medicines to prevent blood clots (anticoagulants);
• the patient or anyone in their immediate family has had blood clots in the legs, lungs, or other organs in the past;
• there is systemic lupus erythematosus;
• the patient has been diagnosed with cancer.

If symptoms of a blood clot occur, see "If any of the following diseases occur during HRT, it is recommended to stop taking Novofem immediately and consult a doctor" and contact your doctor immediately.
Comparison
In women aged 50-59 who do not take HRT, the estimated number of cases of blood clots in the veins over 5 years is 4 to 7 per 1000 women.
In women aged 50-59 who take estrogen-progestogen HRT, the number of cases over 5 years will be 9 to 12 per 1000 (i.e., 5 additional cases).

Coronary artery disease and heart attack

There is no evidence that HRT helps prevent heart attacks. In women over 60 years of age taking estrogen-progestogen HRT, there is a slightly increased tendency to develop coronary artery disease compared to women not taking HRT.

Ischemic stroke

The risk of stroke is about 1.5 times higher in women taking HRT compared to those not taking it. The risk of stroke is strongly related to age, so the number of additional stroke cases caused by HRT will increase with age.
Comparison
In women aged 50-59 who do not take HRT, the estimated number of stroke cases over 5 years is 8 per 1000 women.
In women aged 50-59 who take HRT, the number of cases over 5 years will be 11 per 1000 women (i.e., 3 additional cases).

Other conditions

HRT does not prevent memory loss. The risk of memory loss may be slightly higher in women who start HRT at an age over 65. You should consult your doctor.

Novofem and other medicines

Some medicines may affect the effectiveness of Novofem. This may lead to irregular bleeding. These include:

• antiepileptic drugs(such as phenobarbital, phenytoin, and carbamazepine);
• antituberculosis drugs(such as rifampicin and rifabutin);
• medicines used in HIV infection(such as nevirapine, efavirenz, ritonavir, and nelfinavir);
• medicines used in hepatitis C(such as telaprevir);
• herbal medicines containing St. John's Wort(Hypericum perforatum).

HRT may affect the action of other medicines:

• antiepileptic drug (lamotrigine), which may cause an increase in seizure frequency;
• medicines used in hepatitis C (HCV; e.g., ombitasvir/paritaprevir/ritonavir with dasabuvir or without dasabuvir, as well as glecaprevir/pibrentasvir) may cause an increase in liver blood test results (increase in liver enzyme ALT) in women taking combined hormonal contraceptives containing ethinyl estradiol. Novofem contains estradiol, not ethinyl estradiol. It is not known whether taking Novofem with this hepatitis C treatment regimen may increase liver enzyme ALT.

Other medicines may increase the effect of Novofem:

• medicines containing ketoconazole(an antifungal medicine).

Novofem may affect concurrent cyclosporin treatment.
You should tell your doctor or pharmacistabout all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription, herbal medicines, or other natural products. Your doctor will advise you on this matter.

Lab tests

If a blood test is necessary, you should inform your doctor or laboratory staff about taking Novofem. The medicine may affect the results of some tests.

Novofem with food and drink

Tablets can be taken with or without food and drink.

Pregnancy and breastfeeding

Pregnancy:Novofem is intended for use in postmenopausal women only.
If pregnancy is detected, you should stop taking Novofem immediately and consult your doctor.
Breastfeeding:you should not take Novofem while breastfeeding.

Driving and using machines

The effect of Novofem on driving and using machines is unknown.

Important information about some of the ingredients of Novofem

Novofem contains lactose monohydrate. If you have been diagnosed with intolerance to some sugars, you should contact your doctor before taking Novofem.

3. How to take Novofem

This medicine should always be taken exactly as prescribed by your doctor. If you are unsure, ask your doctor or pharmacist.
In women who are not taking any other hormone replacement therapy, Novofem can be started on any day. Women who are currently taking another hormone replacement therapy should consult their doctor to determine when to start treatment.

Take one tablet daily, at about the same time.

Each pack contains 28 tablets
Days 1 – 16
Take one red tabletdaily for 16 days.
Days 17 – 28
Take one white tabletdaily for 12 days.
Tablets should be taken with a glass of water.
After finishing the pack, treatment should be continued without interruption. After starting a new pack, bleeding similar to menstruation (period) usually occurs.
The instructions for using the calendar pack are at the end of this leaflet, in the section titled "INSTRUCTIONS FOR USE".
Your doctor will prescribe the lowest possible dose for the shortest possible time to reduce the severity of symptoms. If you think the dose of the medicine is too high or too low, you should consult your doctor.
You should inform your doctor if, after 3 months of treatment, there is no satisfactory relief of symptoms. Treatment should only be continued for as long as the benefits outweigh the risks.

Taking a higher dose of Novofem than recommended

If you have taken more than the recommended dose of the medicine, you should contact your doctor or pharmacist.
Overdose of estrogens may cause breast tenderness, nausea, vomiting, and (or) irregular bleeding from the genital tract. Overdose of progestogens may lead to low mood, fatigue, acne, and excessive hair growth.

Missing a dose of Novofem

If you forget to take a tablet at the usual time, you should take it within the next 12 hours. If more than 12 hours have passed, you should take the next dose at the usual time the next day. Do not take a double dose to make up for the missed tablet.
Missing a dose may increase the likelihood of bleeding or spotting.

Stopping Novofem treatment

If you want to stop taking Novofem, you should consult your doctor, who will explain the consequences of stopping treatment and discuss other possible forms of therapy.
If you have any further questions about taking the medicine, you should ask your doctor or pharmacist.

If surgery is planned

If you are scheduled to have surgery, you should tell the surgeon that you are taking Novofem. It may be necessary to stop taking Novofem 4 to 6 weeks before surgery to minimize the risk of blood clots (see section 2. "Blood clots in the veins (venous thromboembolic disease)"). Before restarting Novofem, you should consult your doctor.

4. Possible side effects

Like all medicines, Novofem can cause side effects, although not everybody gets them.
Women taking HRT are at increased risk of developing the following diseases compared to women not taking HRT:

• breast cancer;
• excessive growth or cancer of the endometrium (endometrial hyperplasia or cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolic disease);
• coronary artery disease;
• stroke;
• likely cognitive impairment (perception, attention, memory), if HRT is started at an age over 65.

For more information, see section 2. "Important information before taking Novofem".

Hypersensitivity and (or) allergy (uncommon side effect - affects 1 to 10 women in 1000).

Although this is an uncommon event, hypersensitivity and (or) allergy may occur. Symptoms of hypersensitivity and (or) allergy may include one or more of the following: hives, itching, swelling, difficulty breathing, low blood pressure (pale and cold skin, rapid heartbeat), dizziness, sweating, which can be symptoms of an anaphylactic reaction and (or) anaphylactic shock.
If any of the above symptoms occur, you should stop taking Novofem and seek medical help immediately.

Very common side effects (affects more than 1 in 10 women)

• headache;
• breast tenderness.

Common side effects (affects no more than 1 in 10 women)

• increased blood pressure, worsening of hypertension;
• vaginal thrush;
• dizziness (central origin), insomnia, depression;
• nausea, abdominal pain, bloating with gas;
• nausea;
• rash, itching;
• genital tract bleeding (see section 2. "Unexpected bleeding");
• enlargement of uterine fibroids (benign uterine tumors);
• edema (swelling of the hands, ankles, and feet);
• weight gain.

Uncommon side effects (affects no more than 1 in 100 women)

• migraine;
• changes in libido (changes in sex drive);
• peripheral arterial thrombosis and thrombophlebitis (blood clot);
• vomiting;
• gallbladder disease or gallstones;
• hair loss (alopecia);
• muscle cramps.

Rare side effects (affects no more than 1 in 1000 women)

• allergic reactions;
• nervousness;
• dizziness (vestibular origin);
• diarrhea;
• bloating;
• acne;
• uterine fibroids (benign uterine tumors).

Unknown frequency (cannot be estimated from available data)

• endometrial hyperplasia (excessive growth of the endometrium);
• excessive hair growth on the body and face;
• restlessness;
• vision disorders;
• seborrhea;
• vaginal itching.

Other side effects of combined HRT

The following side effects have been reported during the use of other HRT medicines:

• various skin disorders:
• skin discoloration, especially on the face or neck, called "pregnancy spots" (chloasma),
• red, painful lumps (erythema nodosum),
• rash, including ring-shaped, red, and swollen patches (erythema multiforme),
• red or purple discoloration of the skin and (or) mucous membranes (purpura);
• dry eyes;
• change in the composition of the tear film.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Novofem

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after "Expiry date". The expiry date refers to the last day of the month.
Do not store above 25°C. Do not store in the refrigerator. To protect from light, store in the outer carton.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Novofem contains

• The active substances are estradiol and norethisterone acetate. The red coated tablets contain 1 mg of estradiol (as estradiol hemihydrate). The white coated tablets contain 1 mg of estradiol (as estradiol hemihydrate) and 1 mg of norethisterone acetate.
• Other ingredients are lactose monohydrate, cornstarch, hydroxypropyl cellulose, talc, and magnesium stearate. The red tablet coating contains hypromellose, talc, titanium dioxide (E171), propylene glycol, and iron oxide red (E172). The white tablet coating contains hypromellose, glycerol triacetate, and talc.

What Novofem looks like and contents of the pack

The tablets are round, 6 mm in diameter. The red tablets have the inscription NOVO 282. The white tablets have the inscription NOVO 283.
Each pack of 28 tablets contains 16 red tablets and 12 white tablets.
Pack sizes:

• 28 coated tablets

Marketing authorization holder and manufacturer

Novo Nordisk A/S
Novo Allé
DK–2880 Bagsværd, Denmark

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Member States of the European Economic Area: Novofem - except:
France: Novofemme
Spain: Duofemme
Date of last revision of the leaflet:09/2024

Other sources of information

Detailed information about this medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products http://www.urpl.gov.pl .

INSTRUCTIONS FOR USE

How to handle the calendar pack

1. Setting the day indicator

Turn the inner dial so that the day of the week is opposite the small plastic flap.

2. How to remove the first tablet

Break off the plastic flap and remove the first tablet.

3. Next tablets

The next day, turn the transparent dial in the direction of the clock hands, as indicated by the arrow. Remove the next tablet. Remember to take only 1 tablet per day.

The outer, transparent part can only be turned after the pack has been emptied of the tablet in the recess.