Primolut-Nor 5 mg tablets

Patient Information Leaflet

Introduction

Patient Information Leaflet

Primolut-Nor 5 mg tablets

Norethisterone acetate

Package leaflet contents

1. What Primolut-Nor 5 mg is and what it is 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. How to store Primolut-Nor 5 mg
6. Contents of the pack and other information

1. What Primolut-Nor 5 mg is and what it is 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—lining of 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 must not take Primolut-Nor if any of the following situations apply. If any of these conditions appear for the first time while you are using Primolut-Nor, you must stop treatment immediately and consult your doctor.

• If you are pregnant or suspect you might be pregnant.
• If you are breastfeeding.
• 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 indicate: (i) a future heart attack (e.g., angina pectoris, which causes severe chest pain that may radiate to the left arm) or (ii) a stroke (e.g., a transient ischemic attack, a minor stroke that leaves no lasting effects).
• If you have one major risk factor or several risk factors for developing blood clots.
• If you have (or have had in the past) a certain type of migraine (with focal neurological symptoms such as visual disturbances, 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 severe liver disease, as long as liver function test results have not returned to normal.
• If you have yellowish pigmentation of the eyes and skin (jaundice) due to an inherited condition (Dubin-Johnson or Rotor syndrome), or if you experienced jaundice and/or severe itching during previous pregnancies.
• History of blistering skin rashes during previous pregnancies (pemphigoid gestationis or herpes gestationis).
• If you have hepatitis C and are taking medications containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see also Use of Primolut-Nor 5 mg with other medicines).
• If you have or have had liver tumors (benign or malignant).
• If you have or are suspected of having a hormone-dependent malignant condition.
• If you are allergic to the active substance or to any of the other components of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before starting Primolut-Nor.

The sex steroid (progesterone) contained in this medicine is partially converted into estrogen. Therefore, general warnings associated with combined oral contraceptives should be considered in addition to those specific to Primolut-Nor.

You should take special care while taking Primolut-Nor in certain situations, and your doctor may need to examine you periodically.

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

• If you develop migraine-type headaches for the first time, or if unusually severe headaches increase in frequency.
• If you experience sudden disturbances in perception.
• If you have early signs of thrombophlebitis or thromboembolic symptoms (such as unusual pain or swelling in the leg(s), chest pain, or unexplained shortness of breath or cough).
• If you feel pain or tightness in the chest.
• If you are scheduled for major surgery (treatment should be stopped six weeks before surgery).
• If you will be immobilized for a prolonged period (e.g., after an accident or surgical procedure).
• If jaundice (yellowing of the whites of the eyes and skin) appears, or if you develop 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 chloasma (brownish skin patches). This may occasionally occur, especially if you have a history of chloasma during pregnancy. If you are prone to chloasma, you should avoid exposure to sunlight or ultraviolet radiation 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 previously experienced a type of depression called endogenous depression. Your doctor should consider stopping treatment if severe depression occurs.

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

• If you have a condition that first appeared during pregnancy or previous use of hormonal contraceptives: jaundice (yellowing of the whites of the eyes and skin), generalized itching, kidney stones, a blood disorder called porphyria, systemic lupus erythematosus, a nervous disorder with involuntary movements (Sydenham's chorea), blistering skin rash during pregnancy (herpes gestationis), or hearing loss.
• If you have hereditary angioedema. You should seek medical attention immediately if you experience symptoms of angioedema such as swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, along with difficulty breathing.
• If you have liver disease.
• If you have Crohn's disease or ulcerative colitis (inflammatory bowel disease).

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

• Vascular disorders (of blood vessels)

The use of medicines 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 risk of thromboembolic disorders is higher if you have previously experienced them.

The risk of thromboembolism is also increased during the postpartum period (the time following childbirth until the genital organs and general condition of the woman return to their pre-pregnancy state).

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

Venous thromboembolism (a thromboembolic disorder affecting the veins), manifesting as deep vein thrombosis and/or pulmonary embolism (when a blood clot travels to the lungs and blocks blood vessels), may occur during use of any combined oral contraceptive.

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

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

• Age.
• If you are overweight.
• If a close relative (sibling, parent) has had a blood clot in the leg, lungs, or other organ, or has had a heart attack or stroke at a young age.
• If you are undergoing surgery, have suffered a serious injury, or will be immobilized for a prolonged period. It is important to inform your doctor in advance that you are taking Primolut-Nor, as treatment may need to be stopped. Your doctor will advise you when to restart Primolut-Nor, usually two weeks after regaining mobility.
• If you smoke: you are strongly advised to stop smoking while using Primolut-Nor, especially if you are over 35 years old.
• If you have high cholesterol or triglyceride levels in your blood.
• If you have high blood pressure.
• If you have migraine.
• If you have heart problems (valve disorders, cardiac rhythm disturbances).

Consult your doctor if you are in any of the following situations while taking Primolut-Nor:

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

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

• Severe pain and/or swelling in one leg

• Sudden, severe chest pain, possibly radiating to the left arm

• Sudden shortness of breath

• 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

Breast cancer has been observed slightly more frequently in women using combined contraceptives, but it is not known whether this is due to the treatment. For example, more tumors may be detected in women using combined contraceptives because they are examined by a doctor more frequently. The risk of breast tumors gradually decreases after stopping combined hormonal contraceptives. It is important to have regular breast examinations, and you should see your doctor if you notice any lump.

Benign liver tumors have been reported rarely, and malignant ones even more rarely, in users of hormonal substances such as those contained in Primolut-Nor. In isolated cases, these tumors have caused life-threatening intra-abdominal hemorrhage. Consult your doctor if you experience unusually severe abdominal pain.

? Medical supervision

Before starting or resuming treatment with Primolut-Nor, your doctor must perform a complete medical history and a thorough physical and gynecological examination to rule out contraindications (see section “Do not take Primolut-Nor 5 mg”) and to identify any precautions (see section “Warnings and precautions”). These examinations should be repeated periodically during treatment, at intervals determined by your doctor.

• Laboratory tests

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

Use of Primolut-Nor 5 mg with other medicines

Inform your doctor or pharmacist if you are currently using, have recently used, or might need to use any other medicine.

Some medicines:

• may affect blood levels of Primolut-Nor.
• may reduce its effectiveness.
• 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 and hepatitis C virus 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 conditions, high blood pressure (calcium channel blockers, e.g., verapamil, diltiazem)

• arthritis, osteoarthritis (etoricoxib)

• high blood pressure in the blood vessels of the lungs (bosentan)

• herbal preparations containing St. John’s wort (a herbal remedy mainly used for the treatment of depressive mood states)

• grapefruit juice

Primolut-Nor may influence the effect of other medicines, for example:

• medicines containing cyclosporine
• the antiepileptic lamotrigine (which could lead to an increased frequency of seizures)
• theophylline (used to treat breathing problems)
• tizanidine (used to treat muscle pain and/or muscle spasms)

Do not use Primolut-Nor if you have hepatitis C and are taking medicines containing ombitasvir/paritaprevir/ritonavir and dasabuvir, as this may cause an increase in liver function blood test results (elevated liver enzyme ALT). Treatment with Primolut-Nor may be resumed approximately 2 weeks after completion of this treatment (see section Do not take Primolut-Nor).

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

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

Driving and using machines

There is no information or there are no data available on the effects of Primolut-Nor on the ability to drive or operate machinery.

Primolut-Nor 5 mg contains lactose

This medicine contains lactose. If your doctor has informed you of an intolerance to certain sugars, consult with him before taking this medicine.

3. How to take Primolut-Nor 5 mg

Follow exactly the instructions for use of this medicine as given by your doctor. If you are unsure, please consult your doctor or pharmacist again.

Remember to take your medicine. Your doctor will tell you how long to take treatment with Primolut-Nor. Do not stop treatment early, as the desired effect may not be achieved.

The tablets should be swallowed whole with some liquid.

If you require additional contraceptive protection, you must use non-hormonal contraceptive methods (barrier methods, for example, a condom).

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

Your doctor will determine the dose you should take and will instruct you to take estrogen-containing medicines for about 14 days before starting treatment with Primolut-Nor. After that, you will take between 5 and 10 mg of norethisterone acetate per day (maximum, two tablets of Primolut-Nor 5 mg per day) for 10 days, thus completing the treatment. Menstruation will occur a few days after taking the last tablet.

In patients with endogenous estrogen production, administer 5 mg of norethisterone acetate twice daily from day 16 to day 25 of the cycle, bearing in mind that the first day of menstruation is considered day 1 of the cycle.

For the treatment of endometriosis (growth of endometrium—tissue lining the uterus—outside the uterus):

Treatment should begin between day 1 and day 5 of the cycle with 5 mg of norethisterone acetate twice daily. In case of spotting, the dose may be increased to 10 mg of norethisterone acetate twice daily (two tablets of Primolut-Nor 5 mg twice daily), reducing back to the initial dose if bleeding (or spotting) stops. Treatment should be maintained for at least 4 to 6 months. With daily uninterrupted dosing, you will likely not experience ovulation or menstruation.

Another dosage strength is available on the market for different dosage regimens.

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

If you have taken more Primolut-Nor than you should, contact your doctor or pharmacist immediately or call the Toxicology Information Service (Tel: 91 562 04 20), stating the medicine and amount taken. 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 tell you when to take Primolut-Nor. If you think you have missed a dose, contact your doctor as soon as possible.

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

If you stop treatment with Primolut-Nor 5 mg

There are no specific withdrawal symptoms associated with stopping treatment with Primolut-Nor, but there is a possibility that your original symptoms may recur.

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

4. Possible adverse effects

Like all medicines, Primolut-Nor can cause adverse effects, although not everyone experiences them.

Adverse effects are more common during the first months of treatment and decrease as the duration of treatment increases.

Below is a list of adverse effects, organized by body systems and frequencies, which have been reported in patients treated with Primolut-Nor. However, a causal relationship between the adverse 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 (scant menstrual flow)

These adverse effects have only been reported when the medicine is administered for the treatment of endometriosis (growth of endometrial tissue—the tissue lining 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 medicine is administered for the treatment of endometriosis (growth of endometrial tissue—the tissue lining 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 available data

• Thromboembolism (formation of blood clots in blood vessels)
• Liver tumors leading to intra-abdominal hemorrhage
• Chloasma (brownish skin pigmentation)
• Migraine-type headaches or increased frequency of unusually severe headaches, sudden disturbances in perception, early signs of thrombophlebitis or thromboembolic symptoms (such as unusual pain or swelling in the leg/legs, chest pain, or unexplained shortness of breath or cough), chest pain or tightness, onset of jaundice (yellowing of the whites of the eyes and skin), liver inflammation without jaundice, generalized pruritus (itching), significant increase in blood pressure.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Primolut-Nor 5 mg

Keep this medicine out of the sight and reach of children.

Store in the original packaging to protect from light.

Do not use this medicine after the expiry date which is stated on the packaging after "EXP". The expiry date is the last day of the month indicated.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If you are in doubt, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Primolut-Nor 5 mg

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

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

Appearance of the product and contents of the pack

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

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation 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 the most recent review of this leaflet: April 2019.

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