ANDROCUR 50 mg TABLETS

Introduction

Package Leaflet: Information for the User

Androcur 50 mg Tablets

ciproterone, acetate

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in the package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Androcur and what is it used for
2. What you need to know before taking Androcur
3. How to take Androcur
4. Possible side effects
5. Storage of Androcur
6. Package Contents and Additional Information

1. What is Androcur and what is it used for

Androcur is a medication that belongs to the group of antiandrogens (medications that block the action of male hormones).

Men

Androcur is used in men to:

• Reduce increased sexual drive.

To reduce increased sexual drive in adult men, you should only take ciproterone acetate 50 mg if your doctor considers that other interventions are inappropriate.

• Treat inoperable prostate cancer.
• Reduce male hormone levels at the start of treatment with GnRH agonist medications (gonadotropin-releasing hormone).
• Treat hot flashes caused by decreased male hormone levels.

Women

Androcur is used in women to treat:

• Severe manifestations of androgenization (increased effect of male hormones), such as excessive body hair, significant hair loss, often accompanied by severe acne and/or seborrhea (excessive oily secretion of skin glands).

For the increased effect of male hormones in women described above, you should only take ciproterone acetate 50 mg when satisfactory results have not been achieved with products containing ciproterone acetate in lower doses or with other treatment options.

2. What you need to know before taking Androcur

Do not take Androcur

• For the treatment of reduced increased sexual drive (indication in men), do not take Androcur in the following circumstances:

• if you are allergic (hypersensitive) to ciproterone acetate or any of the other components of this medication (listed in section 6).
• if you have any liver disease.
• if you have Dubin-Johnson syndrome or Rotor syndrome (alteration of bilirubin metabolism, a substance produced by the liver).
• if you have or have had liver tumors.
• if you have any disease that causes severe physical deterioration.
• if you have severe chronic depression.
• if you have or have had thromboembolic events (formation of blood clots in the bloodstream).
• if you have severe diabetes with vascular alterations.
• if you have sickle cell anemia (a type of anemia in which red blood cells have an altered shape).
• if you have ever been diagnosed with a meningioma (a usually benign tumor of the membranes between the brain and the skull). You should consult your doctor if you have any doubts.

• For the treatment of inoperable prostate cancer (indication in men), do not take Androcur in the following circumstances:

• if you are allergic (hypersensitive) to ciproterone acetate or any of the other components of this medication (listed in section 6).
• if you have any liver disease.
• if you have Dubin-Johnson syndrome or Rotor syndrome (alteration of bilirubin metabolism, a substance produced by the liver).
• if you have or have had a liver tumor not due to prostate cancer metastasis.
• if you have any disease that causes severe physical deterioration, except for inoperable prostate cancer.
• if you have severe chronic depression.
• if you have or have had thromboembolic events (formation of blood clots in the bloodstream).
• if you have ever been diagnosed with a meningioma (a usually benign tumor of the membranes between the brain and the skull). You should consult your doctor if you have any doubts.

• For the treatment of severe manifestations of androgenization (indication in women), do not take Androcur in the following circumstances:

• if you are allergic (hypersensitive) to ciproterone acetate or any of the other components of this medication (listed in section 6).
• if you are pregnant.
• if you are breastfeeding.
• if you have any liver disease.
• if you have Dubin-Johnson syndrome or Rotor syndrome (alteration of bilirubin metabolism, a substance produced by the liver).
• if you have had jaundice or persistent itching during any pregnancy.
• if you have had herpes gestationis (herpes related to pregnancy).
• if you have or have had liver tumors.
• if you have any disease that causes severe physical deterioration.
• if you have severe chronic depression.
• if you have or have had thromboembolic events (formation of blood clots in the bloodstream).
• if you have severe diabetes with vascular alterations.
• if you have sickle cell anemia (a type of anemia in which red blood cells have an altered shape).
• if you have ever been diagnosed with a meningioma (a usually benign tumor of the membranes between the brain and the skull). You should consult your doctor if you have any doubts.

When you are taking Androcur for the treatment of severe manifestations of androgenization (indication in women) and are also taking a combined oral contraceptive (medications to prevent pregnancy that contain two types of hormones called estrogens and progestogens), you should also consider and pay attention to the contraindications of the contraceptive.

Warnings and Precautions

Consult your doctor or pharmacist before starting to take Androcur.

• Androcur is not recommended for use in male children and adolescents under 18 years of age, as safety and efficacy have not been established in this patient group.

Androcur should not be administered before the end of puberty (usually around 18 years of age), as it may have an unfavorable effect on growth and hormone production.

• Your doctor should monitor liver function before and during treatment with Androcur, especially if any symptoms or signs suggesting liver damage are observed. Additionally, your doctor should monitor adrenal gland function and blood cell count.

• Tell your doctor if you have diabetes, as Androcur may also interact with oral antidiabetics or insulin (medications for the treatment of diabetes). This disease requires strict medical monitoring (see section "Do not take Androcur").

• The use of ciproterone acetate has been associated with the development of a usually benign brain tumor (meningioma). The risk increases especially when used for a prolonged period (several years) or for a shorter period at high doses (25 mg per day and higher). If you are diagnosed with a meningioma, your doctor will interrupt your treatment with ciproterone acetate (see section "Do not take Androcur"). If you notice symptoms such as changes in vision (e.g., double or blurred vision), hearing loss or ringing in the ears, loss of smell, headaches that worsen over time, memory loss, seizures, or weakness in arms or legs, you should immediately inform your doctor.

Your doctor will reassess the benefit-risk ratio of your treatment when you reach menopause.

• In the treatment of severe manifestations of androgenization (indication in women):

• Before starting treatment, your doctor should perform a thorough gynecological examination (including breasts and cervical cytology study). In women of childbearing age, it must be ensured that they are not pregnant.
• If vaginal bleeding or spotting occurs during treatment with combined oral contraceptives, consult your doctor. Consult the package leaflet of the contraceptive before starting to take the medication.

• During high-dose Androcur treatments, difficulty breathing (dyspnea) may occur. This situation may not require treatment, but if it occurs, consult your doctor.

• In patients treated with Androcur, thromboembolic events (formation of blood clots in the bloodstream) have been reported, although a causal relationship has not been established. If you have had a previous stroke or advanced malignant neoplasm (cancer), you are at higher risk of experiencing thromboembolic events.

• In the treatment of reduced increased sexual drive (indication in men):

• If you consume alcohol, the effect of Androcur may decrease.

• In the treatment of inoperable prostate cancer (indication in men):

• If you have had any type of thrombosis or embolism, sickle cell anemia, or severe diabetes with vascular alterations, your doctor should carefully consider the risk-benefit ratio before deciding on treatment with Androcur.

• Animal data suggest that high doses of Androcur may decrease the function of the hormone-producing glands adjacent to the kidneys (adrenal glands). Therefore, your doctor may perform some tests to monitor this effect during treatment with Androcur.

• In male patients, cases of anemia have been reported during treatment with Androcur. Therefore, your doctor will monitor your red blood cell count during treatment.

Other Medications and Androcur

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

Certain medications may interact with each other, and it may be necessary to change the dose or interrupt treatment with one of the medications.

It is especially important that you inform your doctor if you are using any of the following medications, as they may alter the efficacy of Androcur:

• ketoconazole, itraconazole, clotrimazole (for the treatment of fungal infections).
• ritonavir (for the treatment of HIV infection).
• rifampicin (an antibiotic).
• phenytoin (for the treatment of epilepsy).
• products containing St. John's Wort (for the treatment of depression).

Consult your doctor if you are being treated with statins (medications used to reduce blood cholesterol levels), as the risk of myopathy or rhabdomyolysis (muscle disorders) associated with this treatment may increase if administered simultaneously with Androcur.

Pregnancy, Breastfeeding, and Fertility

Consult your doctor or pharmacist before using any medication.

Do not take Androcur if you are pregnant or breastfeeding.

Driving and Using Machines

Androcur may cause fatigue and decreased vitality, which may reduce your ability to drive and use machinery.

Androcur 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 Androcur

Follow your doctor's instructions for taking Androcur exactly. Consult your doctor or pharmacist if you have any questions.

Remember to take your medication.

Your doctor will indicate the duration of your treatment with Androcur. Do not stop treatment before, as Androcur may not have the desired effect.

THE RECOMMENDED DOSE IN MEN

• Reduction of increased sexual impulse:

The tablets are swallowed with some liquid, after meals. Treatment is usually started with 100 mg/day (1 tablet twice a day). It may be necessary to increase the dose to 200 mg/day (2 tablets twice a day), or even 300 mg/day (2 tablets 3 times a day) for a short period of time. After achieving a satisfactory result, an attempt should be made to maintain the therapeutic effect with the lowest possible dose. Usually, a dose of 50 mg/day (half a tablet twice a day) is sufficient. Your doctor will decide on the possible reduction of the dose or the suspension of the medication, neither of which should be done abruptly but rather gradually, reducing the daily dose to 1 or even half a tablet in stages over several weeks.

To stabilize the therapeutic effect, it is necessary to take Androcur for a long period of time, if possible with the simultaneous use of psychotherapeutic measures.

• Antiandrogenic treatment in inoperable prostate carcinoma:

200-300 mg/day (2 Androcur tablets 2 or 3 times a day).

The tablets are swallowed with some liquid after meals.

Treatment should not be interrupted or the dose reduced after improvement or resolution.

• To reduce the increase in male hormones that occurs when starting treatment with GnRH agonist medications (gonadotropin-releasing hormone):

Initially 200 mg/day (2 tablets twice a day) for 5-7 days, only. Then 200 mg/day (2 tablets twice a day) for 3-4 weeks, administered together with the GnRH agonist at the recommended dose.

• To treat hot flashes in patients undergoing treatment with GnRH analog medications (gonadotropin-releasing hormone) or who have undergone orchiectomy (surgery to remove one or both testicles):

50-150 mg/day (1-3 tablets a day) with a possible increase in the dose to 300 mg/day (2 tablets 3 times a day) if necessary.

THE RECOMMENDED DOSE IN WOMEN

• Women of childbearing age

Androcur should not be taken during pregnancy. Therefore, before starting treatment, your doctor must rule out the existence of pregnancy.

In women of childbearing age, treatment is started on the first day of the cycle (= first day of withdrawal bleeding, also called menstruation). Only in the case of amenorrhea (absence of menstruation) can treatment be started immediately. In this case, the first day of treatment will be considered the first day of the cycle, and the following recommendations will be observed as in the normal case.

On days 1 to 10 of the cycle (for 10 days), 2 Androcur tablets (100 mg/day) will be taken once a day, swallowed with some liquid after a meal. Additionally, fertile women will receive a combined oral contraceptive (preferably cyproterone-ethinylestradiol) from day 1 to 21 of the cycle, in order to ensure necessary contraceptive protection and stabilize the cycle.

Women receiving combined oral contraceptive treatment will always take it at the same time.

After 21 days of daily intake of the combined oral contraceptive, 7 days will be left without taking contraceptives, and during those days, withdrawal bleeding (menstruation) will occur. Exactly four weeks after starting treatment (on day 1), i.e., on the same day of the week, a new cycle of treatment will begin (Androcur for the first 10 days of the cycle, and the combined oral contraceptive for the first 21 days of the cycle), regardless of whether the bleeding has stopped or not.

After achieving clinical improvement, your doctor may reduce the daily dose of Androcur to 1 or half a tablet (50 or 25 mg/day) during the 10 days of continued treatment with the combined oral contraceptive (i.e., the first 10 days of the cycle). It may be possible that after this, treatment with only the combined oral contraceptive (cyproterone-ethinylestradiol) will be sufficient.

Your doctor will reassess the benefit/risk ratio of your treatment when you reach menopause.

Prolonged use (years) of Androcur should be avoided (see section "Warnings and precautions").

Absence of withdrawal bleeding

If withdrawal bleeding (menstruation) does not occur during the medication-free interval, treatment should be interrupted until it is ensured that there is no pregnancy.

• Postmenopausal women or those who have undergone hysterectomy (removal of the uterus)

In postmenopausal women or those who have undergone hysterectomy (removal of the uterus), Androcur can be administered alone, without associated contraceptive treatment. Depending on the severity of the symptoms, the average dose would be 1 or half a tablet of Androcur once a day (50 or 25 mg/day) for 21 days, followed by a 7-day medication-free interval.

Elderly patients

There are no data suggesting the need for a dose adjustment in elderly patients.

Patients with hepatic impairment

Do not take Androcur if you have hepatic impairment.

Patients with renal impairment

There are no data suggesting the need for a dose adjustment in patients with renal impairment.

If you take more Androcur than you should

There is no specific treatment for overdose. If an overdose occurs, the patient should be treated symptomatically and supportive measures should be instituted as necessary.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service. Phone 915 620 420, indicating the medication and the amount used.

If you forget to take Androcur

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

Consult your doctor, who will indicate how to proceed.

Forgetfulness of a tablet in women of childbearing age

Women receiving combined oral contraceptive treatment will always take it at the same time. If more than 12 hours have passed since the usual time of taking the combined oral contraceptive (preferably cyproterone-ethinylestradiol), contraceptive protection may be reduced in that cycle.

You should consult the prospectus of the combined oral contraceptive (preferably cyproterone-ethinylestradiol), especially the parts about contraceptive efficacy and recommendations in case of forgotten tablets. If after that cycle, bleeding does not occur, it should be checked that there is no pregnancy before resuming tablet intake.

If you forget to take an Androcur tablet, it may decrease the therapeutic efficacy and may cause intermenstrual bleeding. Nevertheless, you should continue administering Androcur and the combined oral contraceptive (preferably cyproterone-ethinylestradiol) according to the administration instructions, discarding the forgotten Androcur tablet or tablets (do not take two Androcur tablets to make up for the forgotten dose).

However, during that cycle, a non-hormonal contraceptive method (excluding rhythm and temperature methods) should be used in addition.

If you interrupt treatment with Androcur

Consult your doctor before interrupting treatment with Androcur.

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

4. Possible adverse effects

Like all medications, this medication can cause adverse effects, although not all people experience them.

If you notice any of the following symptoms, inform your doctor immediately:

• Feeling of general discomfort, fever, nausea, vomiting, loss of appetite, itching all over the body, yellowish color of the skin and eyes, yellowish stools, and dark urine. These symptoms can be signs of liver toxicity, including liver inflammation (hepatitis) or liver failure.

• Liver function alterations have been reported, some of which are severe (hepatitis and liver failure), in some cases with a fatal outcome. Liver function alterations are related to the dose and usually occur months after starting treatment. Therefore, your doctor will monitor liver function before starting treatment and during treatment, especially if there are any symptoms or signs suggesting liver toxicity. If liver toxicity is confirmed, your doctor will usually interrupt treatment with Androcur, unless liver toxicity can be explained by another cause (e.g., secondary tumors). In this case, your doctor may continue treatment with Androcur if the observed benefit outweighs the risk.

• Abdominal pain that does not disappear spontaneously in a short period. These symptoms can be signs of benign or malignant liver tumors, which can lead to internal bleeding.

• Inflammation of the calf or leg, chest pain, shortness of breath, or sudden weakness. These symptoms can be signs of blood clots (thromboembolic events).

There have been reports of meningioma associated with long-term use (years) of cyproterone acetate at doses of 25 mg/day and higher.

Adverse effects in women:

The most frequently reported adverse reactions in women treated with Androcur are bleeding or spotting, weight gain, and depressive mood.

Adverse effects associated with the use of Androcur in women, which may occur with a frequency unknown(the frequency cannot be estimated from the available data), are listed below:

• benign and malignant liver tumors
• allergic reactions (hypersensitivity)
• weight gain, weight loss
• depressive mood, temporary restlessness, increased sexual desire (increased libido), decreased sexual desire (decreased libido)
• blood clots (thromboembolic events - see section Be careful with Androcur)
• breathing difficulties
• internal bleeding (intra-abdominal hemorrhage)
• liver toxicity, including jaundice, liver inflammation (hepatitis), liver failure
• skin rash
• inhibition of ovulation, painful breasts, bleeding, fatigue.

Rare(may affect up to 1 in 1,000 patients): meningioma.

In women, ovulation is inhibited under combined treatment, resulting in a state of infertility.

Regarding the additional use of a combined oral contraceptive, attention should be paid to the information in the prospectus about adverse effects.

Adverse effects in men:

Adverse effects associated with the use of Androcur in men are listed below:

• Very common adverse effects(may affect more than 1 in 10 patients):
• • reversible inhibition of spermatogenesis (sperm production)
  • decreased sexual desire (decreased libido)
  • inability to achieve or maintain an erection (erectile dysfunction)

• Common adverse effects(may affect up to 1 in 10 patients):
• • weight gain, weight loss
  • depressive mood, temporary restlessness
  • breathing difficulties
  • liver toxicity, including jaundice (yellowish skin color), liver inflammation (hepatitis), liver failure
  • abnormal breast enlargement
  • fatigue, hot flashes, sweating

• Uncommon adverse effects(may affect up to 1 in 100 patients):
• • skin rash.

• Rare adverse effects(may affect up to 1 in 1,000 patients):
• • allergic reaction (hypersensitivity).
  • meningioma.

• Very rare adverse effects(may affect up to 1 in 10,000 patients):
• • benign and malignant liver tumors.

• Adverse effects of unknown frequency(the frequency cannot be estimated from the available data):
• • low blood cell count
  • blood clots (thromboembolic events in the bloodstream)
  • internal bleeding (intra-abdominal hemorrhage)
  • osteoporosis (bone disease characterized by decreased bone density).

During treatment with Androcur, there is a decrease in sexual desire and potency, as well as an inhibition of the function of the sexual organs. These changes are reversible after stopping treatment.

Over the course of several weeks, Androcur inhibits the ability to produce sperm, which is gradually recovered a few months after stopping treatment.

In men, Androcur can cause gynecomastia (abnormal breast enlargement), sometimes with increased breast sensitivity, which usually disappears after stopping the medication.

As with other antiandrogenic treatments, osteoporosis may occur.

High-dose treatment may reduce adrenal cortical function (hormone secretion in the cerebral cortex and adrenal glands).

Reporting adverse effects

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

5. Storage of Androcur

Keep this medication out of sight and reach of children.

No special storage conditions are required.

Store in the original packaging.

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

Medications should not be thrown away in drains or trash. Deposit the packaging and medications you no longer need in the SIGRE collection point at the pharmacy. If in 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 Androcur

• The active ingredient is cyproterone acetate. Each tablet contains 50 mg of cyproterone acetate.
• The other components are: lactose monohydrate, cornstarch, povidone 25,000, colloidal anhydrous silica, magnesium stearate.

Appearance of the product and package contents

Androcur is presented in white to pale yellow, round, scored tablets, with a hexagon and the letters "BV" engraved on the front.

Packaging with 50 tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder

Advanz Pharma Limited

Unit 17, Northwood House,

Northwood Crescent,

Dublin 9,

D09 V504,

Ireland

Manufacturer

DELPHARM LILLE SAS

Parc d'Activités Roubaix-Est

22 Rue de Toufflers

CS 50070

59452 Lys-Lez-Lannoy

France

Or

BAYER WEIMAR GmbH & Co KG

Döbereiner Strasse 20

Weimar – Germany.

Local representative

Advanz Pharma Spain S.L.U.

Paseo de la Castellana 135, 7th floor

28046 Madrid

Spain

Phone: +34 900 834 889

[email protected]

Date of the last revision of this prospectus:June 2020

Other sources of information

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