Package Leaflet: Information for the User

Primolut-Nor 5 mg Tablets

Norethisterone Acetate

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

2.What you need to know before you start 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 additional information

It belongs to a group of medicines called progestogens.

It is indicated for secondary amenorrhea (secondary lack of menstruation) and endometriosis (growth of endometrium - tissue that covers the uterus - outside the uterus).

Do not take Primolut-Nor 5 mg

Do not take Primolut-Nor if you are pregnant or suspect you may be pregnant.

• If you are pregnant or suspect you may be pregnant.
• If you are breastfeeding.
• If you have (or have had in the past) a heart attack or a stroke (caused by a blood clot or the 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 (for example, angina pectoris, which causes a severe pain in the chest that can extend to the left arm) or (ii) a stroke (for example, a mild stroke that does not leave any sequelae, called "transient ischemic attack").
• If you have a significant risk factor or multiple risk factors for forming blood clots.
• If you have (or have had in the past) a certain type of migraine (with the so-called focal neurological symptoms, such as visual symptoms, difficulty speaking, or weakness or numbness in any part of the body).
• If you have diabetes mellitus combined with circulatory problems.
• If you have or have had a severe liver disease, unless liver function test values have normalized.
• If you have jaundice (yellowing of the eyes and skin) due to a hereditary disease (Dubin-Johnson and Rotor syndromes), or if you have had jaundice and/or intense itching in previous pregnancies.
• History of blisters on the skin during previous pregnancies (pemphigoid or herpes gestational).
• 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 liver tumors (benign or malignant).
• If you have or suspect you have any hormone-dependent malignancy.
• If you are allergic to the active ingredient or to any of the other components of this medication (including those listed in section 6).

Warnings and precautions

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

The steroid sex hormone (progesterone) contained in this medication is partially converted to estrogen. Therefore, the general warnings associated with the use of combined oral contraceptives should also 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 you experience migrainous-type headaches or an unusually intense headache for the first time.
• If you experience sudden changes in perception.
• If you experience the first signs of thrombophlebitis or thromboembolic symptoms (such as unusual pain or inflammation in the legs, chest pain or shortness of breath without apparent cause).
• If you experience chest pain or tension.
• If you are scheduled for major surgery (the treatment should be interrupted six weeks before surgery).
• If you will be immobilized for an extended period (for example, after an accident or surgery).
• If you experience jaundice (yellowing of the eyes and skin), or liver inflammation without jaundice.
• If you experience generalized itching.
• If your blood pressure increases significantly and persistently.

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

• If you have diabetes (a metabolic disorder with high blood sugar levels).
• If you have melasma (brown skin patches). This can occur occasionally, especially if you have a history of melasma during pregnancy. If you are prone to melasma, avoid exposure to the sun 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 an increased risk of developing pancreatitis (inflammation of the pancreas).
• If you have had a type of depression called endogenous depression in the past. Your doctor should evaluate the suspension of treatment if you experience severe depression.

You should also consult your doctor if the following conditions arise or worsen during the use of Primolut-Nor:

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

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

• Vascular disorders (blood vessel disorders)

The use of medications containing progestagens (including noretisterone) and estrogens is associated with an increased frequency of thromboembolic disorders or thromboembolism (formation of blood clots in blood vessels). The increased risk of thromboembolism is higher if you have already experienced it in the past.

The formation of blood clots in veins can be fatal in 1-2% of cases.

Deep vein thrombosis and/or pulmonary embolism (when the blood clot migrates to the lungs and blocks the blood vessels) can occur during the use of any combined oral contraceptive.

Very rarely, blood clots can form in other parts of the body, such as the liver, intestines, kidneys, brain, or eye.

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

• Age.
• Being overweight.
• If one of your close relatives (brother, father, or mother) has had a blood clot in the leg, lungs, or any other organ, or if you have had a heart attack or stroke at a young age.
• If you are undergoing surgery, have had a serious accident, or will be immobilized for an extended period. It is essential to inform your doctor that you are taking Primolut-Nor in advance, as the treatment may need to be interrupted. Your doctor will tell you when to start taking Primolut-Nor again, usually two weeks after regaining mobility.
• If you smoke: you are strongly advised to quit smoking while taking 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, arrhythmia).

Consult your doctor if you are 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 disorder that causes kidney damage).
• If you have inflammatory bowel disease (Crohn's disease or ulcerative colitis).
• If you have sickle cell disease (a genetic disorder of red blood cells).
• If you experience an increase in the frequency or intensity of migraines.
• If you have a hereditary predisposition to venous or arterial thrombosis.

Stop taking Primolut-Nor and immediately consult your doctor if you notice possible signs of blood clots, such as:

• Severe pain and/or inflammation in one of your legs
• Severe and sudden chest pain that can extend to the left arm
• Sudden difficulty breathing
• Sudden cough without apparent cause
• Unusual headache, severe, or prolonged
• 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

Cancer of the breast has been observed slightly more frequently in women using combined hormonal contraceptives, but it is not known whether this is due to the treatment. For example, tumors may be detected more frequently in women using combined hormonal contraceptives because they are examined by their 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 consult your doctor if you notice any lump.

In rare cases, benign tumors have been reported in the liver, and more rarely, malignant tumors, in users of hormonal substances like those contained in Primolut-Nor. In isolated cases, these tumors have caused intra-abdominal hemorrhage with life-threatening risk.Consult your doctor if you experience severe abdominal pain.

?Medical recognition

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

• Laboratory tests

The use of progestagen-type medications can affect the results of certain laboratory tests. If you are instructed to undergo 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 used recently, or may need to use any other medication.

Some medications

• may affect the blood levels of Primolut-Nor.
• mayreduce its effectiveness.
• may cause unexpected bleeding.

These include:

• medications used to treat:

• epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate)
• tuberculosis (e.g. rifampicin)
• infections with HIV and hepatitis C (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, osteoarthritis (etoricoxib)
• high blood pressure in the pulmonary blood vessels (bosentan)

• herbal preparations containing St. John's Wort (a plant used primarily to treat depressive states)
• grapefruit juice

Primolut-Nor may affect the effect of other medications, for example:

• medications containing ciclosporin
• the antiepileptic lamotrigine (which could cause an increase in seizure frequency)
• theophylline (to treat respiratory problems)
• tizanidine (to treat 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 can cause an increase in liver function test results (elevated ALT levels). Primolut-Nor treatment can be resumed approximately two weeks after completing this treatment (see sectionDo not take Primolut-Nor).

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you suspect you may be pregnant, consult your doctor or pharmacist before using this medication.

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

Driving and operating machinery

No information is available or known about how Primolut-Nor affects driving or operating machinery.

Primolut-Nor 5 mg contains lactose

This medication contains lactose. If your doctor has indicated that you have a lactose intolerance, consult with them before taking this medication.

Follow exactly the administration instructions of this medication indicated by your doctor. 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 discontinue treatment beforehand, as the desired effect may not be achieved.

The tablets should be swallowed whole with a small amount of liquid.

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

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

Your doctor will indicate the dose you should take and will instruct you to take medications with estrogens 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 endometrium - tissue that covers the uterus - outside the uterus):

Treatment should start 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), reducing the initial dose if bleeding (or spotting) stops. Treatment should be maintained for at least 4 to 6 months. With daily uninterrupted intake, you are likely to have neither ovulations nor menstruations.

There is another dose available in 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 Toxicological Information Service (Tel: 91 562 04 20), indicating the medication and the amount used. It is recommended to bring the packaging and 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 compensate for the missed 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 may reappear.

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

Like all medications, Primolut-Nor can cause side effects, although not everyone will experience them.

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

The following side effects, listed by body system and frequency, have been described in patients treated with Primolut-Nor, although a causal relationship between the side effect and the treatment has not always been established.

Very common: may affect more than 1 in 10 people

• uterine/vaginal bleeding including spotting, hypomenorrhea (light menstrual bleeding)

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

Common: may affect up to 1 in 10 people

• headache
• nausea
• amenorrhea (absence of menstruation)

This side effect has only been reported when the medication is administered for the treatment of endometriosis (growth of endometrial tissue 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 available data

• thromboembolism (formation of blood clots in blood vessels)
• liver tumors that have led to intra-abdominal hemorrhages
• melasma (brown skin patches)
• migraine-type headaches or increased frequency of severe headaches, sudden changes in perception, initial signs of thrombophlebitis or thromboembolic symptoms (such as unusual pains or inflammation of the legs, chest pain or shortness of breath without apparent cause), sensation of chest pain or tension, 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 side effects

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

Keep this medicationout of the 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.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

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 contents of the packaging

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

Holder of the marketing authorization and responsible manufacturer

Holder of the marketing authorization

Bayer Hispania, S.L.

Av. Baix Llobregat, 3 – 5

08970 Sant Joan Despí – Barcelona

Spain

Responsible manufacturer

Bayer Weimar GmbH und Co. KG

Döbereiner Str. 20

99427 Weimar

Germany

Last review date of this leaflet: April 2019.

The detailed information of this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es