Ketoconazole Esteve

Package leaflet: Information for the patient

Ketoconazole Esteve 200 mg tablets

ketoconazole
This medicinal product is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of 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 others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Ketoconazole Esteve is and what it is used for

Ketoconazole Esteve is a medicine containing the active substance ketoconazole with anti-corticosteroid activity.
It is used for the treatment of endogenous Cushing's syndrome (a condition in which the body produces an excess of cortisol) in adults and adolescents over 12 years of age.
Cushing's syndrome is caused by the overproduction of a hormone called cortisol, which is produced by the adrenal glands. Ketoconazole Esteve is able to block the activity of enzymes responsible for cortisol synthesis, thereby reducing the excessive production of cortisol by the body and improving the symptoms of Cushing's syndrome.

2. What you need to know before taking Ketoconazole Esteve

Do not take Ketoconazole Esteve

• if you are allergic to ketoconazole and/or any antifungal medicine containing imidazole, or to any of the other ingredients of this medicine (listed in section 6)
• if you have liver problems
• if you are pregnant
• if you are breastfeeding
• if you have previously had irregular heartbeat
• if you are taking any of the following medicines:
• certain medicines to lower blood cholesterol: simvastatin, atorvastatin, lovastatin
• certain medicines for the heart: eplerenone, dronedarone, disopyramide, felodipine, nisoldipine, ranolazine
• certain medicines used to treat malaria: quinidine, halofantrine
• certain medicines used for severe mental disorders and severe depression: pimozide, sertindole, lurasidone, quetiapine
• certain medicines used for allergies: mizolastine
• dabigatran – a medicine used to prevent blood clots
• certain medicines that help sleep and treat anxiety: triazolam, alprazolam, midazolam (taken orally)
• certain medicines used for migraine attacks: dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergonovine (methylergonovine)
• certain medicines used in cancer: irinotecan, everolimus
• sirolimus: used to prevent rejection after kidney transplant
• tolvaptan used for a specific condition called “syndrome of inappropriate antidiuretic hormone secretion”
• vardenafil in men over 75 years of age – a medicine to treat erectile dysfunction in adult men
• certain medicines for HIV: saquinavir/ritonavir, saquinavir
• certain medicines for the long-term (chronic) treatment of hepatitis C (a liver infection caused by hepatitis C virus): paritaprevir/ombitasvir (ritonavir)
• methadone: a medicine to treat drug addiction
• In patients with kidney problems:
• colchicine: a medicine to treat gout
• fesoterodine and solifenacin: medicines to treat symptoms of overactive bladder
• telithromycin and clarithromycin: medicines used to treat infections

Do not take Ketoconazole Esteve if any of the above apply to you. If you have any doubts, consult your doctor or
pharmacist before taking Ketoconazole Esteve.
Warnings and precautions
Talk to your doctor or pharmacist before taking Ketoconazole Esteve.
Liver disease
Consult your doctor if you have previously had liver disease. You should know that your liver enzyme levels will
be monitored regularly before starting treatment, weekly during the first month after starting Ketoconazole Esteve,
and then monthly for 6 months due to the risk of severe hepatotoxicity. Afterwards, your levels will be checked
again if your doctor increases your daily dose of ketoconazole. You must stop treatment and contact your doctor
immediately if you feel unwell or develop symptoms such as loss of appetite, nausea, vomiting, fatigue, jaundice,
abdominal pain, or dark urine.
Specific dosing regimen
If you are receiving glucocorticoid replacement therapy along with treatment with Ketoconazole Esteve, your
doctor will advise you on how to adjust your glucocorticoid dose in case of stress, surgery, or infection. You
should also receive an emergency card and carry an emergency glucocorticoid kit with you.
Adrenal function
Your adrenal function will be monitored at regular intervals, according to standard care for monitoring therapy
of Cushing's syndrome, since adrenal insufficiency may occur during treatment. You must contact your doctor
immediately if you develop symptoms such as weakness, fatigue, loss of appetite, nausea, vomiting, or low
blood pressure.
Heart disease
Ketoconazole Esteve may alter your heartbeat – even severely. Contact your doctor immediately if you
experience palpitations or irregular heartbeat during treatment.
Coexisting inflammatory/autoimmune disorders
Inform your doctor if you suffer from an autoimmune disorder. You will require closer monitoring.
Children and adolescents
This medicine is not recommended for children under 12 years of age due to lack of data in these patients.
Other medicines and Ketoconazole Esteve
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Some medicines must not be taken with Ketoconazole Esteve (see section 2). Consult your doctor or pharmacist
for further information if you are taking Ketoconazole Esteve together with other medicines.
Some medicines that may interact with Ketoconazole Esteve:

• pasireotide, another medicine used to treat a subtype of Cushing's syndrome, because it may cause serious adverse effects in patients with heart disorders
• oral medicines that prevent blood clot formation: rivaroxaban, apixaban, edoxaban, cilostazol, warfarin and other coumarins
• HIV medicines such as maraviroc, indinavir, nevirapine, ritonavir
• certain anticancer medicines, such as vinca alkaloids, busulfan, docetaxel, erlotinib, imatinib, dasatinib, sunitinib, lapatinib, nilotinib, bortezomib, paclitaxel, vincristine, vinblastine, cabozantinib, dabrafenib, cabazitaxel, crizotinib, ibrutinib
• certain medicines used to treat infections: rifabutin, telithromycin, rifampicin, isoniazid, clarithromycin, isavuconazole
• certain antidiabetics: repaglinide, saxagliptin, tolbutamide
• certain medicines used for mental disorders: buspirone, aripiprazole, haloperidol, reboxetine, risperidone
• certain heart medicines – verapamil, digoxin, nadolol, aliskiren
• certain antiepileptics: carbamazepine, phenytoin
• certain glucocorticoids, such as budesonide, fluticasone, dexamethasone, methylprednisolone, ciclesonide
• certain strong analgesics (narcotics), such as alfentanil, fentanyl, buprenorphine (by injection and sublingual), oxycodone
• certain medicines used for nausea and vomiting: domperidone, aprepitant
• naloxegol (for the treatment of constipation specifically caused by strong analgesics)
• solifenacin, fesoterodine in patients with kidney problems
• others: sildenafil, tolterodine, mitotane, praziquantel, eletriptan, salmeterol, bosentan, midazolam (by injection), tadalafil, vardenafil, temsirolimus, cinacalcet, tacrolimus, ebastine, cyclosporine, colchicine

You must not take antacids (e.g., aluminium hydroxide) or other medicines for acid indigestion within at least
2 hours after taking Ketoconazole Esteve (see section Warnings and precautions).
Ketoconazole Esteve and alcohol
Do not consume alcoholic beverages during treatment with ketoconazole.
Pregnancy, breastfeeding and fertility
Do not take this medicinal product during pregnancy. If you are pregnant, suspect you may be pregnant, plan
to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Do not breastfeed while taking Ketoconazole Esteve.
Driving and using machines
Dizziness or drowsiness have been reported during treatment with Ketoconazole Esteve. Do not drive or operate
machinery if you experience these symptoms.
Ketoconazole Esteve contains lactose
If your doctor has informed you that you have an intolerance to certain sugars, contact them before taking this
medicine.

3. How to take Ketoconazole Esteve

The initiation and monitoring of treatment must be carried out under the supervision of specialists in endocrinology.
Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.
Your doctor will perform a blood test before starting treatment and will repeat it periodically during treatment to detect any abnormalities and to measure your cortisol levels. The dose will be adjusted according to your condition with the aim of restoring normal cortisol levels.
The recommended starting dose is usually 600 mg daily taken by mouth (3 tablets daily, at 3 different times). To restore normal cortisol levels, a daily dose between 400 mg daily (2 tablets) and 1,200 mg daily (6 tablets) taken orally in 2–3 divided doses may be required.

If you take more Ketoconazole Esteve than you should
If you have taken more than the prescribed dose of Ketoconazole Esteve, you must contact your doctor immediately.

If you forget to take Ketoconazole Esteve
Do not take a double dose to make up for the forgotten dose. If you forget to take a dose, take it as soon as you remember. Then continue as prescribed. Do not change the prescribed dose on your own initiative.

If you stop taking Ketoconazole Esteve
If you stop treatment with Ketoconazole Esteve, your cortisol levels may rise again and symptoms may reappear. Therefore, do not stop taking Ketoconazole Esteve unless your doctor tells you to do so.

If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects can be serious. Liver problems may rarely occur (may affect up to 1 in 1,000 people).
Stop taking Ketoconazole Esteve and contact your doctor immediately if you experience any of the following symptoms:

• Severe, prolonged headache or blurred vision
• Severe loss of appetite (anorexia)
• Weight loss
• Nausea or vomiting
• Unusual tiredness or fever
• Stomach pain
• Muscle weakness
• Yellowing of the skin or whites of the eyes
• Unusually dark urine or pale stools

Adrenal insufficiency is common and may be a serious side effect. Ketoconazole Esteve may temporarily reduce the amount of hormones produced by the adrenal glands (cortisol) to below the normal range. Your doctor will correct this effect by using appropriate hormone replacement therapy or adjusting the dose of Ketoconazole Esteve. You must contact your doctor immediately if you develop symptoms such as weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure.

Very common side effects (may affect more than 1 in 10 people):

• Increased levels of liver enzymes in the blood

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

• Nausea • Diarrhea
• Abdominal pain • Skin reactions (itching, rash)
• Vomiting

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

• Allergic reactions, which may rarely be severe • Dizziness
• Sleepiness • Changes in laboratory markers
• Decreased platelet count • Hair loss
• Headache • Fatigue

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

• Pyrexia (fever)

Side effects of unknown frequency (frequency cannot be estimated from the available data):

• Insomnia • Myalgia (muscle pain)
• Nervousness • Arthralgia (joint pain)
• Alcohol intolerance • Menstrual disorders
• Loss of appetite or increased appetite • Azoospermia (absence of spermatozoa)
• Headache • Erectile dysfunction
• Tingling or pricking sensation • Gynaecomastia (enlargement of breast tissue in males)
• Light aversion • Peripheral oedema (swelling of extremities)
• Nosebleeds • Dyspepsia (indigestion)
• Flatulence • Malaise
• Change in tongue colour • Hot flush
• Dry mouth • Transient decrease in testosterone, a male hormone (androgen) produced by the body, mainly in the testes
• Alteration of taste sensation
• Skin redness, dryness, and itching
• Photosensitivity (increased skin reaction to sunlight: redness, itchy rash)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ketoconazole Esteve

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and blister after “Scad.” or “EXP”. The expiry date refers to the last day of the month.
• This medicine does not require any special storage conditions.
• Do not dispose of medicines 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 Ketoconazole Esteve contains

• The active substance is ketoconazole. Each tablet contains 200 milligrams of ketoconazole.
• The other components are maize starch, lactose monohydrate (see section 2), povidone, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate.

Description of the appearance of Ketoconazole Esteve and pack contents
Ketoconazole Esteve is available in packages containing 60 tablets.
The tablet is white to light cream in colour, round, 10 mm in diameter, biconvex.

Marketing Authorisation Holder
Esteve Pharmaceuticals S.A.
Passeig de La Zona Franca 109 Planta 4
08038 Barcelona
Spain

• 34 93 446 60 00

Manufacturer
Centre Spécialités Pharmaceutiques
76-78 avenue du Midi
63800 Courron d’Auvergne
France
or
Polfarmex S.A.
ul. Józefów 9,
99-300 Kutno
Poland

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. In addition, links to other websites on rare diseases and related therapeutic treatments are provided.