Package Insert: Information for the User

Danatrol 50 mg Capsules

danazol

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

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed for you, 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 any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What Danatrol is and for what it is used

2. What you need to know before starting to take Danatrol

3. How to take Danatrol

4. Possible adverse effects

5. Storage of Danatrol

6. Contents of the package and additional information

Danatrol is an effective hormonal medication for the treatment of endometriosis(growth of the mucous membrane that lines the inside of the uterus outside of it).

It also effectively prevents crises in patients who suffer from hereditary angioneurotic edema (accumulation of fluid under the skin).

Do not take Danatrol

- if you are allergic to danazol or any of the other ingredients of this medication (listed in section 6),

- if you are pregnant or breastfeeding,

- if you have porphyria (a disorder related to red blood cells),

- if you have significant kidney (renal), liver (hepatic), or heart (cardiac) problems,

- if you have or have had thrombosis (formation of a blood clot in the circulatory system), or a thromboembolic disease,

- if you have any type of tumor whose growth is affected by hormone agents,

- if you have an abnormal vaginal bleeding that has not been diagnosed,

- do not take Danatrol at the same time as simvastatina.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Danatrol.

Warnings

Inform your doctor if you have or have had previous reactions to medications, especially steroid medications.

Your doctor may instruct you to have periodic blood tests to monitor liver function and blood cell levels.

Treatment should be discontinued if clinically significant adverse effects appear, and particularly if there is any evidence of:

• masculinization (virilization),
• inflammation of the optic nerve (papilledema), headache, visual disturbances, or other signs or symptoms of increased intracranial pressure,
• yellow discoloration of the skin or any other indication of liver dysfunction,
• vascular problems such as thrombosis or thromboembolism.

It should be noted that:

- due to the relationship of danazol with steroids, liver disorders may occur due to prolonged or repeated treatment,

- the use of danazol increases the risk of developing ovarian cancer in patients treated for endometriosis,

- in the event of having to repeat a treatment cycle with Danatrol, your doctor should closely monitor you.

Precautions

Due to its adverse effects and interactions with other medications, inform your doctor if you have any of the following conditions:

• liver or kidney disease,
• cardiovascular problems,
• high blood pressure,
• any situation that may be exacerbated by fluid retention,
• diabetes,
• lipoprotein disorders (alteration in normal blood lipoprotein levels),
• epilepsy,
• a blood disorder called polycythemia (increase in the proportion of red blood cells by blood volume),
• previous marked or persistent androgenic reaction to a previous steroid treatment,
• migraine.

Before starting treatment, it is essential to exclude the presence of hormone-dependent carcinoma, as well as the persistence or increase of breast nodules during treatment.

Treatment should be initiated during menstruation. Women of childbearing age should use an effective non-hormonal contraceptive method during treatment with Danatrol.

This medication may increase skin sensitivity to sunlight. Avoid exposure to the sun (even on cloudy days) and ultraviolet (UVA) lamps while using this medication.

Use in athletes

This medication contains danazol, which may produce a positive result in doping control tests.

Use of Danatrol with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.Your doctor will decide which medication to discontinue or if the dose needs to be modified.

Especially, inform your doctor if you are currently taking:

• anticonvulsants (to treat seizures),
• antidiabetic medications (to treat diabetes),
• oral anticoagulants such as warfarin (medications that help prevent blood clot formation),
• anti-hypertensive medications (medications that reduce blood pressure),
• ciclosporin or tacrolimus (used in transplants),
• steroids (medications related to male sex hormone),
• alfacalcidol (medication to treat hypocalcemia),
• statins (medications to reduce cholesterol).Do not take Danatrol at the same time as simvastatina (see "Do not take Danatrol").

Due to possible interactions with laboratory tests, inform your doctor that you are taking Danatrol for the determination of testosterone or plasma proteins.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before taking this medication.

Pregnancy:

Given that the use of danazol is contraindicated during pregnancy due to the risk of virilization (masculinization) of the female fetus, appropriate measures should be taken in women of childbearing age to exclude the possibility of pregnancy during treatment.

In the event of pregnancy, do not take Danatrol. Inform your doctor if you are pregnant or intend to become pregnant before starting treatment with this medication.

If you think you have become pregnant during treatment with Danatrol, discontinue treatment and consult your doctor.

Since it is essential to ensure that you are not pregnant, treatment with Danatrol should be initiated during menstruation and an effective non-hormonal contraceptive method should be used during treatment with this medication.

Lactation:

Danazol may, theoretically, produce androgenic (masculinizing) effects in infants and therefore, treatment with danazol or breastfeeding should be discontinued.

Do not breastfeed your child while taking this medication.

Driving and operating machinery

The influence of Danatrol on the ability to drive and operate machinery is unlikely.

Danatrol 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 for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

Danatrol must be taken orally.

If you are a fertile woman, start treatment during menstruation to eliminate the possibility of being pregnant. You must use a non-hormonal contraceptive method during Danatrol treatment.

The usual dose is 200 to 800 mg of danazol per day (not exceeding 800 mg per day), divided into 2 to 4 oral doses.

The dose may be higher or lower than indicated, depending on the response obtained.

Always administer the most effective dose.

This medication should not be taken by children or elderly patients.

If you take more Danatrol than you should

Like other medications, an overdose can be hazardous.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested. It is recommended to bring the packaging and medication leaflet to the healthcare professional.

You should remain under observation for any late reactions.

If you forgot to take Danatrol

The best option is to take the missed dose as soon as possible. Do not take the next dose until at least 4 hours have passed, then continue with the schedule indicated by your doctor.

Do not take a double dose to compensate for the missed doses.

Like all medicines, Danatrol may cause side effects, although not everyone will experience them.

Adverse reactions are presented grouped by organ and system classification and by frequency:

Very common: may affect more than1 in 10 patients

Common: may affect up to1 in 10 patients

Uncommon: may affect up to1 in 100 patients

Rare: may affect up to1 in 1,000 patients

Very rare: may affect up to1 in 10,000 patients

Unknown frequency: cannot be estimated from available data.

Blood and lymphatic system disorders

• Rare: increased red blood cell count (polycythemia), decreased white blood cell count (leucopenia), and decreased platelet count (thrombocytopenia).
• Very rare: elevated eosinophil count in blood (eosinophilia), spleen disease (peliosis splenica).

Metabolism and nutrition disorders

• Increased insulin resistance, abnormal glucose tolerance.
• Common: increased appetite.
• Rare: fluid retention.

Mental and behavioural disorders

• Common: mood changes, anxiety, depressive state, nervousness, changes in sexual desire.

Nervous system disorders

• Common: headache, muscle tremors, muscle contractions.
• Rare: dizziness, benign intracranial hypertension.
• Very rare: worsening of epilepsy, migraine, pain in the wrists and fingers (carpal tunnel syndrome).

Eye disorders

• Rare: visual disturbances such as blurred vision, difficulty focusing, discomfort wearing contact lenses, and refractive changes requiring correction.

Ear and labyrinth disorders

• Rare: vertigo.

Cardiac disorders

• Rare: palpitations and tachycardia. Cases of myocardial infarction have also been reported.

Vascular disorders

• Common: hot flushes.
• Rare: hypertension. Cases of effects caused by the presence of a blood clot in a blood vessel (including sagittal sinus thrombosis, cerebral vascular thrombosis, and arterial thrombosis) have also been observed.

Respiratory, thoracic and mediastinal disorders

• Common: voice change.
• Very rare: interstitial pneumonitis, chest pain.

Gastrointestinal disorders

• Common: nausea.
• Rare: pancreatitis.
• Very rare: upper abdominal pain.

Hepatobiliary disorders

• Rare: jaundice (cholestatic jaundice), benign liver tumor (benign hepatic adenoma).
• Very rare: liver disorders (malignant liver tumor and peliosis hepatica) in cases of prolonged use.
• Unknown frequency: liver cell damage, liver function deterioration, yellowing of the skin and/or mucous membranes due to liver cell injury (hepatocellular jaundice), benign liver tumor (focal nodular hyperplasia of the liver).

Skin and subcutaneous tissue disorders

• Common: skin eruptions that may be accompanied by fever. Cases of facial swelling (edema facial) and increased skin sensitivity to sunlight (photosensitivity) have also been reported. Acne, oily skin (seborrhea), significant facial or body hair growth (hirsutism), hair loss.
• Uncommon: red, elevated skin rashes (urticaria).
• Very rare: inflammatory skin disease (erythematous nodular inflammatory nodule), skin pigmentation disorders, dermatitis exfoliativa, and skin reaction (erythema multiforme).

Musculoskeletal and connective tissue disorders

• Common: back pain, muscle cramps, sometimes accompanied by increased creatine phosphokinase levels, limb pain, joint pain and inflammation.

Renal and urinary disorders

• Very rare: hematuria with prolonged use in cases of hereditary angioedema.

Reproductive and breast disorders

• Common: menstrual cycle disorders, intermenstrual bleeding, amenorrhea, vaginal dryness, vaginal irritation.
• Uncommon: breast shrinkage.
• Rare: clitoral enlargement.
• Very rare: decreased sperm production.

General disorders and administration site conditions

• Rare: fatigue.

Investigations

• Increased plasma glucagon levels, increased LDL cholesterol, decreased HDL cholesterol, and decreased apolipoproteins AI and AII levels.

Other metabolic changes include the induction of ALA synthetase (delta-aminolevulinic acid synthetase) and decreased thyroxine-binding globulin and T4 levels with increased T3 absorption, but without alteration of thyroid-stimulating hormone or free thyroxine levels.

• Common: weight gain.
• Uncommon: isolated increases in liver enzyme levels (transaminases) in blood.
• Rare: increased red and white blood cell counts.

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly to the Spanish System for 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 out of sight and reach of children.

Store below 30°C.

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

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

Composition of Danatrol

- The active ingredient is danazol.Each capsule contains 50 mg of danazol.

• The other components are lactose, cornstarch, talc, and magnesium stearate.

Appearance of the product and contents of the packaging

Opaque pink capsules, with the inscription D50.

Each package contains 60 capsules in a PVC/Aluminum blister.

Holder of the marketing authorization and responsible for manufacturing

Holder

Fidia Farmacéutica S.L.U.

Parque Empresarial de la Moraleja - Torona Building

Avenida de Europa, 24 - Building A - 1 B

28108 Alcobendas - Madrid - Spain

Responsible for manufacturing

Zentiva, k.s.

U Kabelovny 130

102 37 Prague 10

Czech Republic

Last review date of this leaflet: June 2017

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