Danatrol

Package leaflet: Information for the patient

Danatrol 50 mg hard capsules, 200 mg hard capsules

danazol
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Danatrol is and what it is used for
2. What you need to know before taking Danatrol
3. How to take Danatrol
4. Possible side effects
5. How to store Danatrol
6. Contents of the pack and other information

1. What Danatrol is and what it is used for

Danatrol contains danazol, which belongs to a class of medicines called “Antigonadotropins
(pituitary gonadotropin release inhibitor)”.
Danatrol is indicated for:

• the treatment of symptoms and/or reduction of the extent of a disease affecting the uterine mucosa called “endometriosis”. Danatrol may be used either in association with surgery or as sole hormonal therapy in patients who do not respond to other treatments;
• reducing symptoms and pain associated with a breast condition called “fibrocystic mastopathy”. Danatrol should be used only in patients who do not respond to other treatments or for whom other therapies are not recommended;
• a disease characterized by swelling of the face, throat, limbs, possibly causing breathing difficulties, called “hereditary angioedema”.

2. What you need to know before taking Danatrol

Do not take Danatrol

• If you are allergic to danazol or to any of the other ingredients of this medicine (listed in section 6).
• If you are pregnant (see "Pregnancy and breastfeeding").
• If you are breastfeeding (see "Pregnance and breastfeeding").
• If you have abnormal genital bleeding (haemorrhage) without first consulting your doctor.
• If your liver, kidney, or heart function is severely impaired.
• If you suffer from a metabolic disease called "porphyria".
• If you have a type of tumour dependent on certain hormones (androgen-dependent tumour).
• If you have or have previously had a blockage of blood vessels caused by a blood clot (thrombosis or thromboembolic events).
• If you are taking simvastatin (see "Other medicines and Danatrol").

Warnings and precautions
Talk to your doctor or pharmacist before taking Danatrol.
Special caution is needed if you:

• have liver or kidney diseases,
• have high blood pressure (hypertension) or other blood vessel and heart (cardiovascular) diseases,
• suffer from fluid retention,
• have diabetes (diabetes mellitus),
• have a condition characterised by an increase in the volume of red blood cells, called "polycythaemia",
• have epilepsy,
• have abnormalities in certain substances in the body called "lipoproteins",
• have previously experienced adverse reactions (evident or persistent androgenic reactions) after taking sex hormones,
• suffer from migraine.

Your doctor will closely monitor you and carry out laboratory tests, especially if you need to continue treatment with Danatrol for more than 6 months or if you require repeated courses of treatment.
Before starting Danatrol therapy, your doctor:

• will check that you do not have a type of tumour called "hormone-dependent carcinoma",
• will check for breast nodules and monitor any subsequent increase during Danatrol treatment.

Danatrol therapy should be started during menstruation.
Use a reliable non-hormonal contraceptive method (see "Pregnancy and breastfeeding") during treatment with Danatrol.
Your doctor will stop Danatrol treatment if you experience any adverse reaction (see "Possible side effects"), particularly if you have:

• signs of masculinisation due to increased male hormones (virilisation). These symptoms may become irreversible if Danatrol treatment is not discontinued,
• swelling of the area between the optic nerve and the eye called "papilla" (papilledema),
• headache,
• visual disturbances or other symptoms related to increased pressure in the head (such as nausea, vomiting, headache),
• yellowing of the skin and eyes (jaundice) or any other sign of liver disease,
• blockage of a blood vessel due to a blood clot (thrombosis or thromboembolism).

If you need to repeat Danatrol treatment, your doctor will carefully monitor you, as there is a risk of developing benign (benign adenomas, focal nodular hyperplasia) and malignant (carcinomas) liver tumours, and a condition characterised by blood-filled cavities in the liver called "hepatic peliosis".
The use of Danatrol may increase the risk of ovarian cancer in patients treated for endometriosis.
Children
The use of Danatrol is not recommended in children.
Other medicines and Danatrol
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effects of Danatrol may be influenced by, or may influence, the following medicines:

• medicines used for seizures (anticonvulsants) such as carbamazepine, phenytoin, and phenobarbital: Danatrol may affect the response to these drugs;
• medicines for diabetes (antidiabetics): Danatrol may cause insulin resistance;
• oral medicines used to reduce blood clotting (oral anticoagulants): Danazol may enhance the effect of warfarin;
• medicines used for high blood pressure (antihypertensives): Danatrol may reduce their effectiveness;
• cyclosporine and tacrolimus (used mainly after transplants): Danatrol may increase blood levels of these medicines, increasing their toxicity, particularly to the kidney and liver;
• medicines containing steroid hormones: interaction between Danatrol and steroid hormone therapy is likely;
• alfacalcidol, used for diseases due to vitamin D deficiency: Danatrol may increase blood calcium levels in patients with a hormonal disorder called "primary hypoparathyroidism";
• medicines used for cholesterol (statins): Danatrol used together with statins metabolised by the enzyme CYP3A4 increases the risk of muscle disorders (myopathy and rhabdomyolysis). The use of Danatrol together with simvastatin (a medicine belonging to the statin class) is contraindicated (see "Do not take Danatrol").

Danatrol may interact with certain laboratory tests, interfering with the measurement of testosterone or plasma proteins (see "Possible side effects").
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Danatrol is contraindicated during pregnancy because of the risk of masculinisation (virilisation) of a female foetus.
If you are of childbearing age, you must rule out pregnancy before starting Danatrol treatment.
Begin Danatrol therapy during menstruation.
Use a reliable non-hormonal contraceptive method.
If you become pregnant during treatment, Danatrol administration must be stopped immediately.
Breastfeeding
Danatrol may cause masculinisation in breastfed infants; therefore, either Danatrol therapy or breastfeeding must be discontinued.
Driving and using machines
No studies have been conducted on the ability to drive or use machinery.
Danatrol contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
For those engaged in sports activities
Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take Danatrol

Take this medicine by mouth, always following the instructions given by your doctor or pharmacist exactly.
If you have any doubts, consult your doctor or pharmacist.
The treatment cycle must be continuous, without interruptions.
Your doctor will adjust the dose and determine the timing of administration (posology) according to the severity of the disease and your response. Once a satisfactory response has been achieved, your doctor may decide to reduce your dose. Your doctor will always aim to prescribe you the lowest effective dose of Danatrol.
If you are a woman of childbearing potential, start therapy during menstruation, preferably on the first day of your cycle, in order to avoid exposure to the effects of the medicine during pregnancy.
In case of doubt, perform a pregnancy test before starting therapy to rule out the possibility of being pregnant.
If you are a woman of childbearing potential, use a reliable non-hormonal contraceptive method throughout the entire treatment cycle.

In adult female patients
The recommended dose is:

• for the treatment of endometriosis: 200–800 mg per day, in divided doses.

If symptoms are not controlled at lower doses (200–400 mg per day) within 30–60 days, your doctor may decide to increase your dose, which must not exceed 800 mg per day.
The normal duration of treatment is 3 to 6 months.

• for the treatment of fibrocystic mastopathy: 100–400 mg per day, in divided doses.

If symptoms are not controlled at lower doses within 30–60 days, your doctor may decide to increase your dose.
The normal duration of treatment is 3 to 6 months.

In patients of either sex
The recommended dose is:

• for the treatment of hereditary angioedema: 400–600 mg per day. After a two-month period free of attacks, your doctor may decide to reduce your dose to 300 mg or even to 200 mg per day, in divided doses.

In all the conditions described above, two daily administrations are recommended.
Use in the elderly
The use of Danatrol is not recommended in the elderly.
Use in children
The use of Danatrol is not recommended in children.
If you take more Danatrol than you should
Available data suggest that, in case of taking an excessive dose of Danatrol, serious immediate reactions are unlikely.
In case of accidental ingestion/overdose of Danatrol, contact your doctor immediately or go to the nearest hospital.
If you forget to take Danatrol
Do not take a double dose to make up for the missed dose.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Common side effects (may affect up to 1 in 10 people)

• headache,
• nausea,
• vomiting,
• skin redness with spots (maculopapular, petechial or purpuric rash), which may be accompanied by fever, swelling (edema) of the face, light sensitivity, acne, increased sebum production (seborrhoea), increased hair growth (hirsutism), hair loss,
• back pain,
• muscle cramps, sometimes with increased creatine phosphokinase levels,
• muscle tremors,
• muscle twitching (fasciculation),
• limb pain,
• joint pain and swelling,
• hot flushes,
• sweating,
• voice changes,
• weight gain,
• increased appetite,
• absence of menstrual periods (amenorrhoea),
• menstrual cycle disturbances,
• appearance of blood spots between periods (intermenstrual spotting),
• vaginal dryness,
• vaginal burning and itching,
• changes in sexual desire,
• emotional instability,
• anxiety,
• depressed mood,
• nervousness.

Uncommon side effects (may affect up to 1 in 100 people)

• urticaria,
• reduction in breast size,
• increased levels in certain blood tests (transaminases).

Rare side effects (may affect up to 1 in 1,000 people)

• increased blood pressure (hypertension),
• heart rhythm disorders and increased heart rate (palpitations, tachycardia),
• changes in blood cell counts (polycythaemia, leucopenia, thrombocytopenia, increased red blood cell and platelet counts),
• increased intracranial pressure (benign intracranial hypertension),
• dizziness,
• vertigo,
• increased skin sensitivity (hyperaesthesia),
• eye disease called "cataract", leading to decreased transparency of the lens,
• visual disturbances (blurred vision, difficulty focusing, difficulty wearing contact lenses and need for glasses),
• inflammatory disease of the pancreas called "pancreatitis",
• constipation (stipsis),
• bleeding gums,
• blockage of blood vessels due to blood clots (thrombotic events, such as sagittal sinus thrombosis, cerebrovascular thrombosis, arterial thrombosis),
• fluid retention,
• fatigue,
• yellowing of the skin and eyes (cholestatic jaundice),
• benign liver tumours (benign hepatic adenomas),
• enlargement (hypertrophy) of the clitoris.

Very rare side effects (may affect up to 1 in 10,000 people)

• condition characterised by the presence of blood-filled cavities in the spleen (splenic peliosis),
• changes in certain blood cells (eosinophilia),
• a nervous system disorder called "Guillain-Barré syndrome",
• worsening of epilepsy,
• hand pain and numbness (carpal tunnel syndrome),
• migraine,
• stomach pain (epigastric),
• pneumonia (interstitial pneumonia),
• chest pain (pleuritic),
• blood in the urine (haematuria) following prolonged use in patients treated for "hereditary angioedema",
• skin disorders (exfoliative dermatitis, erythema multiforme, erythematous inflammatory nodules, altered skin pigmentation),
• malignant liver tumour and presence of blood-filled cavities in the liver (hepatic peliosis) following prolonged treatment,
• reduced sperm production.

Frequency not known (frequency cannot be estimated from the available data):

• increased insulin resistance,
• increased blood levels of a substance in the body called "glucagon",
• abnormalities in glucose tolerance tests,
• changes in certain blood substances: increased low-density lipoproteins (LDL), decreased high-density lipoproteins (HDL), decreased apolipoproteins AI and AII,
• metabolic effects (induction of delta-aminolevulinic acid (ALA) synthetase and reduction of thyroid hormone-binding globulin and T4, with increased T3 uptake, without interference with thyroid-stimulating hormone or free thyroxine index),
• liver disorders (hepatocellular lesions, liver failure, hepatocellular jaundice, focal nodular hyperplasia of the liver),
• heart attack.

Additional rare side effects in children

• In children, altered bone formation may occur (premature closure of the bone epiphyses).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You may also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Danatrol

Do not store above 30°C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp.". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Danatrol contains
Danatrol 50 mg hard capsules

• The active substance is danazol. Each capsule contains 50 mg of danazol.
• The other components are: maize starch, lactose, talc, magnesium stearate, titanium dioxide, gelatin, red iron oxide.

Danatrol 200 mg hard capsules

• The active substance is danazol. Each hard capsule contains 200 mg of danazol.
• The other components are: maize starch, lactose, talc, magnesium stearate, titanium dioxide, gelatin, red iron oxide, yellow iron oxide.

Description of the appearance of Danatrol and pack contents
Danatrol is available as

• Hard capsules in packs of 30 capsules.

Marketing Authorization Holder
Fidia farmaceutici S.p.A.
Via Ponte della Fabbrica, 3/A
35031 Abano Terme (PD)
Manufacturer
Zentiva k.s. – U Kabelovny 130, 102 37 – Prague 10 – Czech Republic