PRIMOLUT-NOR 5 mg TABLETS

Introduction

Package Leaflet: Information for the User

Primolut-Nor 5 mg Tablets

Norethisterone Acetate

Contents of the Package Leaflet

1. What is Primolut-Nor 5 mg and what is it used for
2. What you need to know before taking Primolut-Nor 5 mg
3. How to take Primolut-Nor 5 mg
4. Possible side effects
5. Storage of Primolut-Nor 5 mg
6. Contents of the pack and further information

1. What is Primolut-Nor 5 mg and what is it used for

It belongs to the group of medicines called progestogens.

It is indicated in secondary amenorrhea (absence of menstruation) and endometriosis (growth of endometrial tissue - tissue that lines the uterus - outside the uterus).

2. What you need to know before taking Primolut-Nor 5 mg

Do not take Primolut-Nor 5 mg

You should not take Primolut-Nor if any of the following conditions are present. If any of these appear for the first time during the use of Primolut-Nor, you should stop treatment immediately and consult your doctor.

• If you are pregnant or think you may be pregnant.
• If you are breast-feeding.
• If you have (or have had in the past) a heart attack or stroke (caused by a blood clot or rupture of a blood vessel in the brain).
• If you have (or have had in the past) a disease that could be indicative of: (i) a future heart attack (e.g. angina pectoris, which causes intense chest pain that can extend to the left arm) or (ii) a stroke (e.g. a mild stroke that leaves no sequelae, called "transient ischemic attack").
• If you have a significant risk factor or several risk factors for forming blood clots.
• If you have (or have had in the past) a certain type of migraine (with so-called focal neurological symptoms, such as visual symptoms, difficulty speaking, or weakness or numbness in some part of the body).
• If you have diabetes mellitus combined with circulatory problems.
• If you have (or have had in the past) a severe liver disease, as long as liver function test values have not normalized.
• If you have yellowing of the eyes and skin (jaundice) due to hereditary disease (Dubin-Johnson and Rotor syndrome), or if you have had jaundice and/or intense itching in previous pregnancies.
• Past history of skin blisters during previous pregnancies (pemphigoid or gestational herpes).
• If you have hepatitis C and are taking medications that contain ombitasvir/paritaprevir/ritonavir and dasabuvir, (see also Use of Primolut-Nor 5 mg with other medications).
• If you have (or have had in the past) liver tumors (benign or malignant).
• If you have (or are suspected to have) any hormone-dependent malignant condition.
• If you are allergic to the active substance or to any of the other components of this medication (included in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Primolut-Nor.

The sex steroid (progesterone) contained in this medication is partially converted to estrogen. Therefore, the general warnings associated with the use of combined oral contraceptives should be taken into account, in addition to those of Primolut-Nor.

In some situations, you should be particularly careful while taking Primolut-Nor, and your doctor may need to examine you periodically.

In any of the following situations, you should contact your doctor as soon as possible, as the use of Primolut-Nor should be interrupted:

• If migraines of the migraine type appear for the first time or if the frequency of unusually intense headaches increases.
• If you have sudden changes in perception.
• If you have the first signs of thrombophlebitis or thromboembolic symptoms (such as unusual pain or inflammation of the leg/s, pain when breathing, or cough without apparent reason).
• If you have a feeling of pain or tension in the chest.
• If you are scheduled to have major surgery (treatment should be interrupted six weeks before surgery).
• If you are going to be immobilized for a prolonged period (e.g. after accidents or surgery).
• If jaundice (yellowing of the whites of the eyes and skin) appears, or liver inflammation without jaundice.
• If you have generalized itching.
• If your blood pressure increases significantly and persistently.

You should be carefully monitored by your doctor in the following situations:

• If you have diabetes (a metabolic disease with high blood sugar levels).
• If you have chloasma (brown spots on the skin). This can occur occasionally, especially if you have a history of chloasma during pregnancy. If you have a tendency to chloasma, you should avoid sun exposure or ultraviolet rays while taking Primolut-Nor.
• If you have high levels of lipids in the blood (hypertriglyceridemia) or a family history of this condition. Hypertriglyceridemia has been associated with a higher risk of developing pancreatitis (inflammation of the pancreas).
• If you have suffered from a type of depression called endogenous depression in the past. Your doctor should assess the suspension of treatment in case of severe depression.

You should also consult your doctor if the following disorders appear or worsen during the use of Primolut Nor:

• If you have any disease that appeared for the first time during pregnancy or previous use of hormonal contraceptives: jaundice (yellowing of the whites of the eyes and skin), generalized itching, kidney stones, a blood disease called porphyria, systemic lupus erythematosus, a nervous disease in which involuntary movements appear (Sydenham's chorea), skin rash with blisters during pregnancy (gestational herpes), hearing loss.
• If you have hereditary angioedema. You should go to your doctor immediately if you experience symptoms of angioedema such as swelling of the face, tongue, and/or pharynx, and/or difficulty swallowing or urticaria, along with difficulty breathing.
• If you have liver disease.
• If you have Crohn's disease or ulcerative colitis (inflammatory bowel disease).

If some of the disorders/risk factors mentioned below are present or worsen, your doctor should assess the benefits of using Primolut-Nor against the possible risks before deciding whether you should start or continue treatment.

• Vascular disorders (of blood vessels)

The use of medications containing progestogens (including norethisterone) and estrogens is associated with an increased frequency of thromboembolic disorders or thromboembolism (formation of blood clots in blood vessels). The increased risk of thromboembolic disorders is greater if you have already suffered from them in the past.

The risk of thromboembolism also increases during the postpartum period (the period from childbirth to when the genital organs and the woman's general condition return to the state before pregnancy).

Blood clot formation in the veins can be fatal in 1-2% of cases.

Venous thromboembolism (thromboembolic disorder that affects the veins), which manifests as deep vein thrombosis and/or pulmonary embolism (when the blood clot moves to the lungs and blocks the blood vessels), can occur during the use of any combined oral contraceptive.

Extremely rarely, blood clots can form in other parts of the body, such as the liver, intestine, kidney, brain, or eye.

The risk of blood clot in veins or arteries or stroke increases with:

• Age.
• If you are overweight.
• If any of your close relatives (brother, father, or mother) have had a blood clot in the leg, lungs, or any other organ, or if they have had a heart attack or stroke at a young age.
• If you are going to have surgery, have had a serious accident, or are going to be immobilized for a prolonged period. It is essential that you inform your doctor in advance that you are taking Primolut-Nor, as treatment may need to be interrupted. Your doctor will tell you when to start taking Primolut-Nor again. This usually happens two weeks after regaining mobility.
• If you smoke: you are strongly advised to quit smoking while using Primolut-Nor, especially if you are over 35 years old.
• If you have high levels of cholesterol or triglycerides in the blood.
• If you have high blood pressure.
• If you have migraines.
• If you have heart problems (valve disorders, cardiac arrhythmia).

Consult your doctor if you find yourself in the following situations while taking Primolut-Nor:

• If you have diabetes.
• If you have systemic lupus erythematosus (a disease of the immune system).
• If you have hemolytic uremic syndrome (a blood disease that causes kidney damage).
• If you have Crohn's disease or ulcerative colitis (inflammatory bowel disease).
• If you have sickle cell disease (a hereditary disease of red blood cells).
• If the frequency or intensity of migraines increases.
• If you have a hereditary predisposition to venous or arterial thrombosis.

Interrupt treatment with Primolut-Nor and go to your doctor immediately if you notice possible signs of blood clot, such as:

• severe pain and/or inflammation in one of your legs
• severe and sudden chest pain, which can reach the left arm
• sudden difficulty breathing
• sudden cough without a clear cause
• unusual, severe, or prolonged headache
• partial or complete loss of vision, or double vision
• difficulty or inability to speak
• dizziness or fainting
• weakness, abnormal sensations, or numbness in any part of the body
• difficulty moving
• severe abdominal pain

• Tumors

It has been observed that breast cancer is slightly more common in women who use combined contraceptives, but it is not known if this is due to the treatment. For example, it may be that more tumors are detected in women who use combined contraceptives because they are examined by the doctor more frequently. The risk of breast tumors decreases gradually after stopping combined hormonal contraceptives. It is essential to undergo regular breast exams, and you should go to your doctor if you notice any lump.

Rarely, benign and, more rarely, malignant liver tumors have been reported in users of hormonal substances like the one contained in Primolut-Nor. In isolated cases, these tumors have caused life-threatening intra-abdominal bleeding. Go to your doctor if you suffer from unusually severe abdominal pain.

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Before starting or resuming treatment with Primolut-Nor, it is necessary for your doctor to perform a complete medical history and physical and gynecological examination, aimed at ruling out contraindications (see section "Do not take Primolut-Nor 5 mg") and observing precautions (see section "Warnings and precautions"). These examinations should be repeated periodically throughout treatment, with the frequency that your doctor deems necessary.

• Laboratory tests

The use of progestogen-type medications can affect the results of certain laboratory tests. If you are prescribed any laboratory test, inform your doctor that you are taking Primolut-Nor.

Use of Primolut-Nor 5 mg with other medications

Inform your doctor or pharmacist that you are using, have recently used, or may need to use any other medication.

Some medications

• may affect Primolut-Nor blood levels.
• may reduce its effectiveness.
• may cause unexpected bleeding.

These include:

• medications used to treat:

• epilepsy (e.g. primidone, phenytoin, barbiturics, carbamazepine, oxcarbazepine, topiramate, felbamate)
• tuberculosis (e.g. rifampicin)
• HIV and hepatitis C infections (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors, e.g. ritonavir, nevirapine, efavirenz)
• fungal infections (griseofulvin, azole antifungals, e.g. itraconazole, voriconazole, fluconazole)
• bacterial infections (macrolide antibiotics, e.g. clarithromycin, erythromycin)
• certain heart diseases, high blood pressure (calcium channel blockers, e.g. verapamil, diltiazem)
• arthritis, arthrosis (etoricoxib)
• high blood pressure in the blood vessels of the lungs (bosentan)

• preparations based on medicinal plants with St. John's Wort (a medicinal plant used mainly for the treatment of depressive states)
• grapefruit juice

Primolut-Nor may affect the effect of other medications, e.g:

• medications containing cyclosporine
• the antiepileptic lamotrigine (which could lead to an increased frequency of seizures)
• theophylline (for treating respiratory problems)
• tizanidine (for treating muscle pain and/or muscle cramps)

Do not use Primolut-Nor if you have hepatitis C and are taking medications that contain ombitasvir/paritaprevir/ritonavir and dasabuvir, as this may cause an increase in liver function test results (increase in liver enzyme ALT). The use of Primolut-Nor can be restarted approximately 2 weeks after the end of this treatment (see section Do not take Primolut-Nor).

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

You should not take Primolut-Nor if you are pregnant or breast-feeding.

Driving and using machines

It is not known how Primolut-Nor affects driving or using machines.

Primolut-Nor 5 mg contains lactose

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

3. How to take Primolut-Nor 5 mg

Follow the administration instructions of this medication indicated by your doctor exactly. In case of doubt, consult your doctor or pharmacist again.

Remember to take your medication. Your doctor will indicate the duration of your treatment with Primolut-Nor. Do not stop treatment before, as the desired effect may not be achieved.

The tablets should be swallowed whole with some liquid.

If you need additional contraceptive protection, you should use non-hormonal contraceptive methods (barrier methods, e.g. a condom).

For the treatment of secondary amenorrhea (absence of menstruation):

Your doctor will indicate the dose you should take and will indicate that you take estrogen medications for about 14 days before starting treatment with Primolut-Nor. From then on, you will take between 5 and 10 mg of norethisterone acetate per day (a maximum of two Primolut-Nor 5 mg tablets per day) for 10 days, thus ending the treatment. Menstruation will occur a few days after taking the last tablet.

In patients with endogenous estrogen production, 5 mg of norethisterone acetate will be administered twice a day, from day 16 to 25 of the cycle, taking into account that the first day of menstruation is considered the first day of the cycle.

For the treatment of endometriosis (growth of endometrial tissue - tissue that lines the uterus - outside the uterus):

Treatment should begin between day 1 and day 5 of the cycle with 5 mg of norethisterone acetate twice a day. In case of spotting, the dose can be increased to 10 mg of norethisterone acetate twice a day (two Primolut-Nor 5 mg tablets twice a day), decreasing to the initial dose if bleeding (or spotting) stops. Treatment should be maintained for at least 4 to 6 months. With daily uninterrupted intake, you will probably not have ovulations or menstruations.

There is another dose on the market for different dosing regimens.

If you take more Primolut-Nor 5 mg than you should

If you have taken more Primolut-Nor than you should, consult your doctor or pharmacist immediately or call the Toxicology Information Service (Tel: 91 562 04 20), indicating the medication and the amount used. It is recommended to bring the package and package leaflet to the healthcare professional.

If you forget to take Primolut-Nor 5 mg

Your doctor will indicate when you should take Primolut-Nor. If you think you have forgotten a dose, contact your doctor as soon as possible.

Do not take a double dose to make up for forgotten doses.

If you interrupt treatment with Primolut-Nor 5 mg

There are no specific symptoms of withdrawal from Primolut-Nor treatment, but there is a possibility that your original disorders will reappear.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, Primolut-Nor can cause adverse effects, although not all people suffer from them.

Adverse effects are more frequent during the first months of treatment and decrease with the duration of treatment.

The following are the adverse effects, listed by body systems and frequencies, which have been described in patients treated with Primolut-Nor, although it has not always been possible to establish a causal relationship between the adverse effect and the treatment.

Very Common: may affect more than 1 in 10 people

• uterine/vaginal bleeding including spotting, hypomenorrhea (scanty menstruation)

These adverse effects have only been reported when the medication is administered for the treatment of endometriosis (growth of endometrial tissue - tissue that lines the uterus - outside the uterus).

Common: may affect up to 1 in 10 people

• headache
• nausea
• amenorrhea (absence of menstruation)

This adverse effect has only been reported when the medication is administered for the treatment of endometriosis (growth of endometrial tissue - tissue that lines the uterus - outside the uterus).

• edema (fluid retention)

Uncommon: may affect up to 1 in 100 people

• migraine

Rare: may affect up to 1 in 1,000 people

• hypersensitivity reactions (allergy)
• urticaria, rash (skin eruption)

Very Rare: may affect up to 1 in 10,000 people

• visual disturbances
• dyspnea (difficulty breathing)

Frequency Not Known: cannot be estimated from the available data

• thromboembolism (formation of blood clots in blood vessels)
• liver tumors that have led to intra-abdominal hemorrhages
• chloasma (brown spots on the skin)
• cephalalgias (headaches) of a migrainous type or increased frequency of unusually intense cephalalgias, sudden changes in perception, first signs of thrombophlebitis or thromboembolic symptoms (such as unusual pain or inflammation of the leg/s, pain when breathing or coughing without apparent reason), feeling of pain or tension in the chest, appearance of jaundice (yellowing of the whites of the eyes and skin), liver inflammation without jaundice, generalized itching, significant increase in blood pressure.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Primolut-Nor 5 mg

Keep this medication out of sight and reach of children.

Store in the original packaging to protect it from light.

Do not use this medication after the expiration date that appears on the packaging after "CAD". The expiration date is the last day of the month indicated.

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medications you no longer need at the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Primolut-Nor 5 mg

The active ingredient is norethisterone acetate. Each tablet contains 5 mg of norethisterone acetate.

The other components (excipients) are: lactose monohydrate, cornstarch, povidone 25000, talc, and magnesium stearate.

Appearance of the Product and Package Contents

• Primolut-Nor 5 mg is available in a box of 30 tablets, with 2 blisters of 15 tablets each.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Bayer Hispania, S.L.

Av. Baix Llobregat, 3 – 5

08970 Sant Joan Despí – Barcelona

Spain

Manufacturer

Bayer Weimar GmbH und Co. KG

Döbereiner Str. 20

99427 Weimar

Germany

Date of Last Revision of this Prospectus: April 2019.

Detailed information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es