Package Leaflet: Information for the User

Androcur 50 mg Tablets

ciproterone, acetate

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

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

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 for:

• To reduce increased sexual drive.

To reduce increased sexual drive in adult men, only take ciproterone acetate 50 mg if your doctor considers other interventions to be inappropriate.

• To treat inoperable prostate cancer.
• To reduce male hormone levels at the start of treatment with GnRH agonist medications.
• To 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), for example, excessive body hair, marked hair loss, often accompanied by severe acne and/or seborrhea (excessive oily secretion of the skin glands).

To treat the increased effect of male hormones in women as described above, 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.

Do not take Androcur

• For the treatment of increased libido (indications in men), do not take Androcur in the following circumstances:

• if you are allergic (hypersensitive) to ciproterone acetate or to 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 processes (formation of clots in the blood circulation).
• 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 of the tissue between the brain and the skull). Consult your doctor if you have doubts.

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

• if you are allergic (hypersensitive) to ciproterone acetate or to 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 that is 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 thromboembolic processes (formation of clots in the blood circulation).
• if you have ever been diagnosed with a meningioma (a usually benign tumor of the membranes of the tissue between the brain and the skull). Consult your doctor if you have doubts.

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

• if you are allergic (hypersensitive) to ciproterone acetate or to 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 yellowing of the skin or mucous membranes (jaundice) or persistent itching during pregnancy.
• if you have had herpes gravidarum (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 processes (formation of clots in the blood circulation).
• 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 of the tissue between the brain and the skull). Consult your doctor if you have doubts.

When you are taking Androcur for the treatment of severe androgenization manifestations (indications in women) and at the same time taking a combined oral contraceptive (medications to prevent pregnancy that contain two types of hormones called estrogens and progestogens), you must also take into account 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 children and adolescents under 18 years old because safety and efficacy have not been established in this group of patients.

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

• Your doctor should control liver function before and during treatment with Androcur, especially if any symptoms or signs suggest liver alteration. In addition, your doctor should control adrenal gland function and blood cell count.

• Inform your doctor if you have diabetes, as Androcur may also interact with oral antidiabetic drugs or insulin (medications for the treatment of diabetes). This disease requires strict medical supervision (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 above). If you are diagnosed with 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 vision or blurred vision), hearing loss or tinnitus, loss of smell, worsening headaches, memory loss, seizures, or weakness in arms or legs, you should immediately inform your doctor.

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

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

• Before starting treatment, your doctor should perform a thorough gynecological examination (including breasts and cytological study of the cervix). In fertile women, it must be ensured that you are not pregnant.
• If during treatment with combined oral contraceptives (medications to prevent pregnancy) you experience vaginal bleeding or spotting, consult your doctor. Consult the prospectus of the contraceptive before starting to take the medication.

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

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

• In the treatment of increased libido (indications in men):

• If you drink alcohol, the effect of Androcur may be reduced.

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

• If you have had any type of thrombosis or embolism, sickle cell anemia (a type of anemia in which red blood cells have an altered shape) or severe diabetes with vascular alterations, your doctor should carefully consider the benefit-risk ratio in each case before deciding on treatment with Androcur.

• The data in animals suggest that high doses of Androcur may decrease the function of the adrenal glands. Therefore, your doctor may perform some tests to control 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

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

Certain medications may interact with each other, in which case it may be necessary to change the dose or discontinue treatment with one of the medications.

It is especially important to inform your doctor if you are using any of the following medications, as they may modify the effectiveness 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 (hypericum) (for the treatment of depression).

Consult your doctor if you are taking statins (medications used to reduce blood cholesterol levels), as the risk of myopathy or rhabdomyolysis (diseases in which muscle disorders occur) 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 operating machinery

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

Follow exactly the administration instructions for Androcur indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

Remember to take your medication.

Your doctor will indicate the duration of your treatment with Androcur. Do not discontinue treatment beforehand, as Androcur may not exert the desired effect.

RECOMMENDED DOSE INMALE

• Increased sexual impulse reduction:

Tablets are taken with a small amount of liquid, after meals. Treatment usually begins with 100 mg/day (1 tablet twice a day). The dose may be adjusted 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, try 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 suspension of medication, neither of which should be done abruptly but gradually, reducing the daily dose to 1 or 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, preferably with the simultaneous use of psychotherapeutic measures.

• Antiandrogenic treatment in inoperable prostate cancer:

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

Tablets are taken with a small amount of 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:

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 with the recommended GnRH agonist.

• To treat hot flashes in patients undergoing treatment with GnRH analog medications or who have undergone orchiectomy:

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

RECOMMENDED DOSE INFEMALE

• Women of childbearing age

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

Treatment begins on the first day of the cycle (= first day of menstrual bleeding, also known as menstruation). In the case of amenorrhea (absence of menstruation), treatment can begin immediately. In this case, the first day of treatment will be considered the first day of the cycle, and the following recommendations will be followed as in the normal case.

From days 1 to 10 of the cycle (for 10 days), 2 Androcur tablets (100 mg/day) will be taken once a day, with a small amount of liquid after a meal. In addition, women of childbearing age will receive a combined oral contraceptive (preferably ciproterone-ethinylestradiol) from day 1 to 21 of the cycle, to ensure necessary contraceptive protection and stabilize the cycle.

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

After 21 days of daily intake of the combined oral contraceptive, 7 days without taking contraceptives will be left, and during those days, menstrual bleeding will occur. Exactly four weeks after starting treatment (day 1), the 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 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) for the 10 days of continued treatment with the combined oral contraceptive (i.e., the first 10 days of the cycle). It may be possible to continue treatment with the combined oral contraceptive (ciproterone-ethinylestradiol) only.

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

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

Lack of menstrual bleeding

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

-Postmenopausal or hysterectomized women (women who have had their uterus removed)

In postmenopausal or hysterectomized women, Androcur can be administered alone, without associated contraceptive treatment. According to 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.

Older patients

No data suggest the need for dose adjustment in older patients.

Patients with liver insufficiency

Do not take Androcur if you have liver insufficiency.

Patients with renal insufficiency

No data suggest the need for dose adjustment in patients with renal insufficiency.

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 compensate for the missed doses.

Consult your doctor, who will indicate how to proceed.

Missing a tablet in women of childbearing age

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

Consult the prospectus of the combined oral contraceptive (preferably ciproterone-ethinylestradiol), especially the parts on contraceptive efficacy and recommendations in case of missed tablets. If no bleeding occurs after that cycle, check for pregnancy before resuming tablet intake.

If you forget to take an Androcur tablet, the therapeutic effect may be reduced and may cause intermenstrual bleeding. However, treatment with Androcur and the combined oral contraceptive (preferably ciproterone-ethinylestradiol) should continue according to the administration instructions, discarding the missed Androcur tablets (do not take two Androcur tablets to compensate for the missed dose).

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

If you interrupt treatment with Androcur

Consult your doctor before interrupting treatment with Androcur.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

• General feeling of 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 may be signs of liver toxicity, including liver inflammation (hepatitis) or liver failure.

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

• Upper abdominal pain that does not resolve spontaneously within a short period of time. These symptoms may be signs of benign or malignant liver tumors, which may be associated with internal bleeding.

• Swelling of the calf or leg, chest pain, shortness of breath, or feeling weak suddenly. These symptoms may be signs of blood clots (thromboembolic events).

There have been reports of meningioma associated with the prolonged use (years) of ciproterone acetate at doses of 25 mg/day and above.

Side effects in women:

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

The side effects associated with the use of Androcur in women, which may occur with anunknown frequency(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 anxiety, increased libido, decreased libido
• Blood clots (thromboembolic events – see sectionBe careful with Androcur)
• Dyspnea
• Internal bleeding (hemorrhage intra-abdominal)
• Liver toxicity, including jaundice, liver inflammation (hepatitis), liver failure
• Skin rash
• Inhibition of ovulation, painful breasts, bleeding, fatigue

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

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

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

Side effects in men:

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

• Very common side effects(may affect more than 1 in 10 patients):
• • Reversible inhibition of spermatogenesis (sperm formation)
  • Decreased libido
  • Inability to achieve or maintain an erection (erectile dysfunction)

• Common side effects(may affect up to 1 in 10 patients):
• • Weight gain, weight loss
  • Depressive mood, temporary anxiety
  • Dyspnea
  • Liver toxicity, including jaundice, liver inflammation (hepatitis), liver failure
  • Abnormal breast enlargement
  • Fatigue, hot flashes, sweating

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

• Rare side effects(may affect up to 1 in 1,000 patients):
• • Allergic reaction (hypersensitivity).
  • Meningioma.

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

• Unknown frequency(the frequency cannot be estimated from the available data):
• • Low blood cell count
  • Thromboembolic events (blood clots in the circulatory system)
  • Internal bleeding (hemorrhage intra-abdominal)
  • Osteoporosis (bone disease characterized by a decrease in bone density).

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

Within several weeks, Androcur inhibits the ability to produce sperm, which recovers gradually several months after stopping treatment.

Androcur may cause gynecomastia (abnormal enlargement of the breasts) in men, sometimes with increased sensitivity to breast rubbing, which usually resolves after stopping medication.

As with other antiandrogen treatments, osteoporosis may occur.

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

Reporting of side effects

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

Keep this medication out of the 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 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 unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Androcur

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

Appearance of the product and content of the container

Androcur is presented in white to pale yellowish round, scored tablets, on the anterior face they bear a hexagon with the letters “BV”.

Containers with 50 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Advanz Pharma Limited

Unit 17, Northwood House,

Northwood Crescent,

Dublín 9,

D09 V504,

Irlanda

Responsible for manufacturing

DELPHARM LILLE SAS

Parc d'Activités Roubaix-Est

22 Rue de Toufflers

CS 50070

59452Lys-Lez-Lannoy

Francia

O

BAYER WEIMAR GmbH & Co KG

Döbereiner Strasse 20

Weimar – Alemania.

Local representative

Advanz Pharma Spain S.L.U.

Paseo de la Castellana 135, 7ª

28046 Madrid

España

Tf: +34 900 834 889

[email protected]

Last review date of this leaflet:June 2020

Other sources of information

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/