Lysodren

Package leaflet: Information for the user

Lysodren 500 mg tablets

mitotane
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, please contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Lysodren is and what it is used for

Lysodren is an antitumour medicinal product that contains the active substance mitotane.
This medicine is used to treat the symptoms of advanced, inoperable, metastatic or recurrent malignant tumours of the adrenal glands.

2. What you need to know before taking Lysodren

Do not take Lysodren

• if you are allergic to mitotane or to any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding. You must not breastfeed during treatment with Lysodren.
• if you are taking medicines containing spironolactone (see "Other medicines and Lysodren").

Warnings and precautions
Talk to your doctor or pharmacist before taking Lysodren.
Inform your doctor if any of the following apply:

• if you have a wound (shock, severe trauma), an infection, or any illness during treatment with Lysodren. Inform your doctor immediately, as they may decide to temporarily suspend treatment.
• if you have liver problems: inform your doctor if you develop any of the following signs and symptoms of liver problems during treatment with Lysodren: itching, yellowing of the eyes or skin, dark urine, or pain or discomfort in the upper right part of the abdomen. Your doctor should perform blood tests to monitor liver function before and during treatment with Lysodren, and whenever clinically indicated. Your doctor may decide to discontinue treatment with Lysodren.
• if you have severe kidney problems.
• if you are taking any of the medicines listed below (see "Other medicines and Lysodren").
• if you have gynecological problems such as vaginal bleeding, menstrual disorders, and/or pelvic pain.

This medicine must not be handled by anyone other than the patient and their caregiver,
especially not by pregnant women. Caregivers must wear disposable gloves
when handling the tablets.
During treatment with Lysodren
Lysodren may temporarily reduce the amount of hormones produced by your adrenal gland
(cortisol), but your doctor will correct this by using appropriate hormone replacement therapy (steroids).
Lysodren may cause prolonged bleeding. If you require surgery or dental procedures during treatment
with Lysodren, your doctor will perform blood tests to assess the risk of prolonged bleeding.
Other medicines and Lysodren
Inform your doctor or pharmacist if you are taking or have recently taken any other
medicines, including those without a prescription.
Lysodren must not be administered in combination with medicines containing
spironolactone, often used as a diuretic in the treatment of cardiac, liver, or renal disorders.
Lysodren may interfere with many medicines. Therefore, you must tell your doctor if you are taking
medicines containing the following active substances:

• warfarin or other anticoagulants (blood thinners), used to prevent blood clots. The dose of the anticoagulant you are taking may need to be adjusted.
• anticonvulsants
• rifabutin or rifampicin, used in the treatment of tuberculosis
• griseofulvin, used to treat fungal infections
• herbal remedies containing St. John's wort ( Hypericum perforatum ).
• sunitinib, etoposide: for cancer treatment
• midazolam, used as a sedative

Lysodren with food and drinks
Lysodren should preferably be taken during meals containing fatty foods,
such as milk, chocolate, or oil.
Pregnancy, breastfeeding and fertility
Lysodren may harm the unborn baby. Therefore, if you are pregnant, think you may be pregnant, or
are planning a pregnancy, inform your doctor as soon as possible to determine whether you should stop or
continue treatment with Lysodren.
If you are a woman of childbearing potential, you must use an effective contraceptive method during
treatment with Lysodren and also after stopping it. Ask your doctor for advice.
Due to the risk of serious adverse reactions in the infant, you must not breastfeed during
treatment with Lysodren and also after stopping it. Ask your doctor for advice.
Driving and using machines
Lysodren has a major influence on the ability to drive vehicles and use machinery. Ask
your doctor for advice.

3. How to take Lysodren

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Dosage, method and duration of administration
At the beginning of treatment, the usual dose for adults is 2–3 g (4 to 6 tablets) daily.
Your doctor may decide to start treatment with higher doses, such as 4–6 g (8 to 12 tablets).
To determine the best dose for you, your doctor will regularly monitor the amount of Lysodren in your blood. Your doctor may decide to temporarily interrupt treatment with Lysodren or to reduce the dose if you experience certain side effects.
Use in children and adolescents
The initial daily dose of Lysodren is 1.5–3.5 g per m² of body surface area (this will be calculated by the doctor based on the child's weight and height). Experience in patients within this age group is very limited.
Method of administration
Take the tablets with a glass of water during meals containing fatty foods. You may divide the total daily dose into two or three administrations.
If you take more Lysodren than you should
Inform your doctor immediately if you have accidentally taken more Lysodren than prescribed, or if a child has accidentally ingested some tablets.
If you forget to take Lysodren
If you have accidentally forgotten to take a dose, take the next dose as prescribed. Do not take a double dose to make up for the missed dose.
If you have any questions 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 everybody gets them.
Contact your doctor immediately if you experience any of the following side effects:

• Adrenal insufficiency: fatigue, abdominal pain, nausea, vomiting, diarrhoea, confusion
• Anaemia: paleness of the skin, muscle fatigue, breathing problems, dizziness especially when standing
• Liver problems: yellowing of the skin and eyes, itching, nausea, diarrhoea, fatigue, dark-coloured urine
• Neurological disorders: movement and coordination problems, abnormal sensations such as tingling, memory loss, difficulty concentrating, difficulty speaking, dizziness

These symptoms may indicate complications requiring specific treatments.
Based on how frequently they occur, side effects are defined as follows:

• very common: may affect more than 1 in 10 people
• common: may affect up to 1 in 10 people
• not known: frequency cannot be estimated from the available data

Very common side effects

• vomiting, nausea (feeling sick), diarrhoea, stomach ache
• loss of appetite
• abnormal sensations such as tingling
• movement and coordination disorders, dizziness, confusion
• drowsiness, fatigue, muscle weakness (muscle fatigue during exertion)
• inflammation (swelling, burning, pain) of mucous membranes, skin rash
• blood abnormalities (prolonged bleeding time)
• increased cholesterol, triglycerides (fats), and liver enzymes (in blood tests)
• decreased white blood cell count
• excessive breast development in men
• adrenal insufficiency (may cause fatigue, abdominal pain, nausea, vomiting, diarrhoea, confusion)

Common side effects

• dizziness, headache
• peripheral nervous system disorders (combination of sensory disturbances, muscle atrophy and weakness, reduced tendon reflex, and vasomotor symptoms such as facial flushing, sweating, and sleep disturbances)
• mental disturbances (such as memory loss, difficulty concentrating)
• movement disorders
• decreased red blood cells (anaemia accompanied by symptoms such as paleness of the skin and fatigue), decreased platelets (may increase tendency to bruising and bleeding)
• hepatitis (autoimmune) (may cause yellowing of the skin and eyes, dark-coloured urine)
• difficulty coordinating muscles

Frequency not known

• fever
• generalized pain
• facial flushing, high or low blood pressure, dizziness/vertigo when standing up quickly
• increased salivation
• eye disorders: vision changes, blurred vision, double vision, distorted images, glare
• opportunistic infections
• liver damage (may cause yellowing of the skin and eyes, dark-coloured urine)
• decreased uric acid levels in blood tests
• bladder inflammation with bleeding
• presence of blood in urine, presence of protein in urine
• balance disorder
• distortion of taste sensation
• disturbed digestion
• ovarian macrocysts (with or without symptoms such as pelvic pain, vaginal bleeding, menstrual disorders)
• reduced androstenedione (a sex hormone precursor) in blood tests in women
• reduced testosterone (sex hormone) in blood tests in women
• increased sex hormone-binding globulin (a protein that binds sex hormones) in blood tests
• increased levels of corticosteroid-binding globulin in blood tests, increased thyroxine-binding globulin in blood tests
• reduced free testosterone (sex hormone) in blood tests in men
• hypogonadism in men (with symptoms such as excessive breast development, decreased libido, erectile dysfunction, fertility disorders)
• allergic reactions, itching

Additional side effects observed in children and adolescents
In children and adolescents, thyroid problems, mental and growth retardation, and one case of encephalopathy have been observed. In addition, some signs of hormonal changes have been observed (such as excessive breast development in males and vaginal bleeding and/or early breast development in females).
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Lysodren

Keep this medicine out of the sight and reach of children.
Store in the original packaging. After first opening: 1 year.
Do not use this medicine after the expiry date which is stated on the carton and on the vial after
Exp.
Unused medicine and waste material derived from this medicine must be disposed of in accordance with
local regulations concerning cytotoxic medicines.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Lysodren contains

• The active substance is mitotane. Each tablet contains 500 mg of mitotane.
• The other components are maize starch, microcrystalline cellulose (E 460), macrogol 3350 and anhydrous colloidal silica.

Description of the appearance of Lysodren and pack contents
Lysodren tablets are white, biconvex, round and engraved.
Lysodren is supplied in plastic bottles containing 100 tablets.
Marketing Authorisation Holder:
Esteve Pharmaceuticals S.A.
Passeig de La Zona Franca 109, 4th floor
08038 Barcelona
Spain
+34 93 446 60 00
Manufacturer:
Latina Pharma S.p.A.
Via Murillo, 7
04013 Sermoneta (LT)
Italy
or
Centre Specialites Pharmaceutiques
76-78, avenue du Midi
63800 Cournon d’Auvergne
France
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and their therapeutic treatments are also provided.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.