• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

• if you are allergic to ketoconazole and/or to any imidazole antifungal medicine, 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 a history of an irregular heart beat
• if you are taking any of the following medicines:
  • certain medicines for lowering blood cholesterol: simvastatin, atorvastatin, lovastatin
  • certain heart medicines: epleronone, dronedarone, disopyramide, felodipine, nisoldipine, ranolazine
  • certain medicines used for the treatment of the paludism: quinidine, halofantrine
  • certain medicines used for severe mental health disorders and severe depression: pimozide, sertindole, lurasidone, quetiapine
  • certain medicines used for the allergies: mizolastine
  • dabigatran – medicine used to prevent the formation of blood clots
  • certain medicines to help to sleep and for anxiety: triazolam, alprazolam, midazolam (taken by mouth)
  • certain medicines used for migraine attacks: dihydroergotamine, ergometrine (ergonovine) ergotamine and methylergometrine (methylergonovine)
  • certain medicines used in cancers: irinotecan, everolimus
  • sirolimus: used to prevent your body from rejecting a kidney transplant
  • tolvaptan used for a specific disease called “syndrome of inappropriate antidiuretic hormone secretion”
  • vardenafil in men older than 75 years – medicine to treat erectile dysfunction in adults men
  • certain medicines for HIV: saquinavir/ritonavir, saquinavir
  • certain medicines to treat long-term (chronic) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus): Paritaprevir/Ombitasvir (ritonavir)
  • methadone: medicine to treat dependence to drugs
  • In patients with renal disorders:
    • colchicine: medicine to treat gout
    • fesoterodine and solifenacin: medicines to treat the symptoms of an overactive bladder
    • telithromycin and clarithromycin: medicine used to treat infections

Do not take Ketoconazole HRA if any of the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Ketoconazole HRA.

Talk to your doctor or pharmacist before taking Ketoconazole HRA.

Liver disease

Speak with your doctor if you have a history of liver disease. You should know that your liver enzyme tests will be regularly monitored before starting the treatment, once weekly during the first month after Ketoconazole HRA initiation and then monthly for 6 months due to the risk of serious hepatic toxicity. They will be checked again after that in case your doctor increases your daily ketoconazole dose. You should stop your treatment and contact your doctor immediately if you feel unwell or experience symptoms such as lack of appetite, nausea, vomiting, fatigue, jaundice, abdominal pain or dark urine.

Specific dosing regimen

If you take concomitant glucocorticoid replacement therapy with your Ketoconazole HRA treatment, your doctor should inform you how to adapt your glucocorticoid replacement therapy dose if you are under stress or have surgery or an infection. In addition, you should receive an emergency card and should be equipped with an emergency glucocorticoid set.

Adrenal function

Your adrenal function will be monitored at regular intervals as this is the standard care in the follow-up of Cushing’s syndrome therapy and since adrenal insuficiency can occur during the treatment. You should contact your doctor immediately if you have symptoms such as weakness, fatigue, lack of appetite, nausea, vomiting or low blood pressure.

Heart disease

Ketoconazole HRA can change how your heart beats – this can be serious. Contact your doctor immediately, if you get palpitations or an irregular heartbeat during treatment.

Coexisting inflammatory/autoimmune disorders

Tell your doctor if you suffer from an autoimmune disorder, you will be closely supervised.

This medicine is not recommended for children under 12 years due to the lack of data in these patients.

Tell your doctor or phamacist if you are taking, have recently taken or might take any other medicines. There are some medicines that must not be taken with Ketoconazole HRA (see section 2). Ask your doctor or pharmacist for more information if you are taking Ketoconazole HRA with other medicines.

Medicines that can interact with Ketoconazole HRA include:

• pasireotide, another drug used to treat a subset of the Cushing’s syndrome because it can lead to severe side effects in patients suffering from cardiac disorders
• medicines taken by mouth that prevent blood clots from forming: rivaroxaban, apixaban, edoxaban, cilostazol, warfarin and others coumarin like
• HIV medicines such as maraviroc, indinavir, nevirapine, ritonavir
• certain medicines used for cancer 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, isoniazide, clarithromycin, isavuconazole
• certain antidiabetics: repaglinide, saxagliptin, tolbutamide
• certain medicines used for mental disorders: buspirone, aripipazole, haloperidol, reboxetine, risperidone
• certain heart medicines – verapamil, digoxin, nadolol, aliskiren
• certain anticonvulsivants: carbamazepine, phenitoin
• certain glucocorticoids – such as budesonide, fluticasone, dexamethasone, methylprednisolone, ciclesonide
• certain stong painkillers (narcotics) – such as alfentanyl, fentanyl, buprenorphine (injection and sublingual), oxycodone
• certain medicines used for nausea and vomiting: domperidone, aprepitant
• naloxegol (medicine for treatment of constipation specifically caused by strong pain medicines)
• solifenacin, fesoterodine in patients with renal impairment
• others: sildenafil, , tolterodine, mitotane, praziquantel, eletriptan, , salmeterol, bosentan, midazolam (by injection), tadalafil, vardenafil, temsirolimus, cinalcacet, tacrolimus, ebastine, ciclosporine, colchicine

You should not take antacids (eg aluminium hydroxide) or other medicines for acid indigestion for at least 2 hours after the intake of Ketoconazole HRA (see section Warning and Precautions).

No alcohol should be consumed during treatment with ketoconazole.

Do not take this medicinal product during pregnancy. If you think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Do not breastfeed your baby if you are taking Ketoconazole HRA.

Dizziness or somnolence have been reported during treatement with Ketoconazole HRA. Do not drive or operate machines if you experience these symptoms.

If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicinal product.

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

Do not take a double dose to make up for a forgotten dose. If you forget to take one dose, take this dose as soon as you remember. Then go on with regular schedule as prescribed. Do not change the prescribed dose yourself.

If you interrupt your treatment with Ketoconazole HRA your cortisol level may increase again and your symptoms may come back. Therefore, do not stop taking Ketoconazole HRA unless your doctor tells you.

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via:

United Kingdom

or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is ketoconazole. Each tablet contains 200 milligram ketoconazole
• The other ingredients are maize starch, lactose monohydrate (see section 2), povidone, microcrystalline cellulose, silica colloidal, magnesium stearate

Ketoconazole HRA is available in packs containing 60 tablets.