ITRACONAZOLE ALTER 100 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Itraconazole Alter 100 mg Hard Capsules EFG

Read this package leaflet carefully before you start taking this medicine, because it contains important information for you

• Keep this package 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 symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Itraconazole Alter and what it is used for
2. What you need to know before you start taking Itraconazole Alter
3. How to take Itraconazole Alter
4. Possible side effects
5. Storing Itraconazole Alter
6. Package Contents and Further Information

1. What is Itraconazole Alter and what it is used for

Itraconazole Alter belongs to a group of medicines called “antifungals”.

It is indicated for the treatment of infections caused by fungi of the vagina, skin, mouth, eyes, nails, or internal organs.

2. What you need to know before taking Itraconazol Alter

Do not take Itraconazol Alter 100 mg capsules

• if you are allergicto itraconazole or to any of the other components of this medicine (included in section 6).
• if you have a disease called heart failure (also called congestive heart failure or CHF). This medicine could worsen it.

If your doctor considers that you should take this medicine, contact him immediately if you notice that you are short of breath, gain weight unexpectedly, have swollen legs, feel unusually tired, or start waking up at night.

• if you are pregnant, think you may be pregnant, or may become pregnant(see pregnancy section) your doctor will assess whether you should take this medicine.

• if you are of childbearing age, you should take adequate contraceptive measures to avoid becoming pregnant during treatment. Because this medicine can stay in the body for a long time, you should extend contraceptive measures until the next menstrual period after finishing treatment with this medicine.
• itraconazole should not be used with some medicines. There are many medicines that interact with Itraconazol Alter, see the section "Other medicines and Itraconazol Alter" and the list below.

Before taking Itraconazol Alter, inform your doctor if you are taking any other medicine.

Do not use Itraconazol Alter ifyou are taking any of the following medicines, or within 2 weeks after finishing Itraconazol Alter:

Medicines used to treat heart, blood, or circulation problems

• aliskiren, eplerenone, lercanidipine, or nisoldipine (for hypertension)
• bepridil, ivabradine, or ranolazine (for angina)
• dabigatran or ticagrelor (for blood clots)
• disopyramide, dofetilide, dronedarone, or quinidine (for irregular heartbeat)
• lomitapide, lovastatin, or simvastatin (to lower cholesterol)
• sildenafil (for pulmonary arterial hypertension)

Medicines for stomach or constipation problems

• cisapride (for stomach disorders)
• domperidone (for nausea and vomiting)
• naloxegol (for constipation caused by taking opioid painkillers)

Medicines for headache, sleep, or mental health problems

• dihydroergotamine or ergotamine (ergot alkaloids used for migraines)
• midazolam (oral) or triazolam (for sedation or sleep induction)
• lurasidone, pimozide, quetiapine, or sertindol (for schizophrenia, bipolar disorder, or other mental health disorders)

Medicines for urinary problems

• darifenacin (for urinary incontinence)
• fesoterodine or solifenacin (for irritated urinary bladder) when used in patients with certain kidney or liver problems

Medicines for allergies

• astemizole, mizolastine, or terfenadine (for allergies)

Medicines for erection and ejaculation problems

• avanafil (for erectile dysfunction)
• dapoxetine (for premature ejaculation)
• vardenafil (for erectile dysfunction) when used in men over 75 years old

Other medicines that contain:

• colchicine (for gout) when used in patients with kidney or liver problems
• ergometrine (ergonovine) or methylergometrine (methylergonovine), ergot alkaloids used after childbirth
• eliglustat (for Gaucher's disease) when used in patients who cannot break down certain medicines in the body
• halofantrine (for malaria)
• irinotecan (for cancer)
• isavuconazole (for fungal infections)
• ombitasvir, paritaprevir, ritonavir with or without dasabuvir (for hepatitis C)

Remember: do not take any of the above medicines during 2 weeks after your last treatment with Itraconazol Alter.

Warnings and precautions

Be especially careful with Itraconazol Alter

• if you have heart problems, consult your doctor. Inform your doctor immediately if you experience difficulty breathing, unexpected weight gain, swelling of the legs, unusual fatigue, or insomnia, as these may be symptoms of heart failure.
• if you have any liver problems. It may be necessary to adjust the dose of this medicine. If any of the following symptoms appear during treatment with this medicine, stop taking it and consult your doctor immediately: loss of appetite, nausea, vomiting, fatigue, abdominal pain, jaundice (yellowing of the skin, eyes, mucous membranes, and secretions), dark urine, or pale stools. If you are undergoing treatment with itraconazole, it is likely that your doctor will order regular blood tests, as liver disorders have occurred in very rare cases.
• if you have any kidney problems, consult your doctor. It may be necessary to adjust the dose of this medicine.
• consult your doctor or seek medical attention immediately if, while taking itraconazole, you have a severe allergic reaction (characterized by a pronounced skin rash, itching, hives, difficulty breathing, and/or swelling of the face).
• stop taking this medicine and consult your doctor immediately if you become too sensitive to sunlight.
• stop taking itraconazole and consult your doctor immediately if you experience a severe skin disorder, such as a widespread rash with skin peeling and blisters in the mouth, eyes, and genitals, or a rash with small blisters or vesicles.
• contact your doctor if you have neutropenia, AIDS, or have received an organ transplant. The dose of this medicine may need to be adjusted.
• if you have had an allergic reaction due to itraconazole or another medicine used to treat fungal infections (medicines known as azoles), consult your doctor. A hypersensitivity reaction can be recognized, for example, by the appearance of a skin rash, itching, hives, shortness of breath, or difficulty breathing, and/or swelling of the face. If you experience a severe allergic reaction, consult your doctor immediately.
• if you have cystic fibrosis, consult your doctor before taking itraconazole.
• stop taking itraconazole and consult your doctor immediately if you experience any sensation of tingling, numbness, decreased sensitivity, or weakness in the extremities or other nerve problems in the arms and legs (neuropathy).
• stop taking this medicine and contact your doctor immediately if you do not hear correctly. In very rare cases, temporary or permanent hearing loss has occurred.
• inform your doctor if your vision becomes blurred or double, if you hear a buzzing in your ears, if you lose control of your urine or urinate more than usual.
• it is not recommended to take this medicine in elderly patients. Only in exceptional cases may it be prescribed by the doctor.

Other medicines and Itraconazol Alter

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medicine, including those obtained without a prescription.

There are medicines that should not be takenwhile taking Itraconazol Alter. These medicines are listed above under the heading "Do not use Itraconazol Alter"

It is not recommended to use certain medicines with Itraconazol Alter

Your doctor may decide that you should not take some medicines at the same time as Itraconazol Alter or in the 2 weeks following its completion.

Examples of these medicines are:

Medicines for heart, blood, or circulation problems

• apixaban, rivaroxaban, or vorapaxar (for blood clots)
• atorvastatin (to lower cholesterol)
• felodipine (for hypertension)
• riociguat or tadalafil (for pulmonary hypertension)

Medicines for epilepsy, headache, or mental health problems

• phenytoin, carbamazepine, or phenobarbital (antiepileptics)
• eletriptan (for migraines)
• St. John's Wort (Hypericum perforatum) (a plant-based medicine used for mental health problems)

Medicines for urinary problems

• tamsulosin (for male urinary incontinence)
• tolterodine (for irritated urinary bladder)

Medicines for cancer

• axitinib, bosutinib, cabazitaxel, cabozantinib, ceritinib, cobimetinib, crizotinib, dabrafenib, dasatinib, docetaxel, ibrutinib, lapatinib, nilotinib, olaparib, pazopanib, regorafenib, sunitinib, trabectedin, trastuzumab emtansine, or vinca alkaloids (e.g., vinflunine, vinorelbine)

Medicines for tuberculosis

• bedaquiline, isoniazid, rifabutin, or rifampicin (for tuberculosis)

Medicines for human immunodeficiency virus (HIV) or hepatitis

• efavirenz or nevirapine (for HIV/AIDS)
• elbasvir/grazoprevir, simeprevir, tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) (for HIV or hepatitis)

Medicines used after organ transplantation

• everolimus, rapamycin (also known as sirolimus), temsirolimus

Medicines for benign prostatic hyperplasia

• alfuzosin, silodosin

Medicines for lung problems, allergies, or inflammatory conditions

• ciclesonide (for inflammation, asthma, and allergies)
• ebastine (for allergies)
• salmeterol (for asthma or chronic obstructive pulmonary disease, COPD)

Medicines for erection and ejaculation problems

• tadalafil or vardenafil (when used in men 75 years or younger) (for erectile dysfunction)

Other medicines that contain:

• colchicine (for gout)
• fentanyl (for pain)
• lumacaftor/ivacaftor (for cystic fibrosis)

Remember: do not take any of the above medicines during 2 weeks after your last treatment with Itraconazol Alter.

This list is not complete, so you should inform your doctor if you are taking or plan to take any of these medicines or any other medicine.

Caution is required when using Itraconazol Alter 100 mg with certain medicines.

You may be more likely to experience side effects or it may be necessary to modify the dose of Itraconazol Alter or the other medicine. Examples of these medicines are:

Medicines for heart, blood, or circulation problems

• bosentan (for pulmonary hypertension)

• calcium channel blockers such as dihydropyridines, such as amlodipine, isradipine, nifedipine, nimodipine, or diltiazem (for hypertension)
• verapamil (for hypertension)
• cilostazol (for circulatory problems)
• "coumarins" such as warfarin (for blood clots)
• digoxin (for atrial fibrillation)
• nadolol (for pulmonary hypertension or angina)

Medicines for stomach or diarrhea problems

• aprepitant or netupitant (for nausea and vomiting during cancer treatment)
• loperamide (for diarrhea)
• antacids such as aluminum, calcium, magnesium, or sodium bicarbonate; H2 receptor antagonists such as cimetidine, ranitidine, and proton pump inhibitors such as lansoprazole, omeprazole, or rabeprazole (for stomach acid problems)

Medicines for sleep disorders or mental health problems

• alprazolam, brotizolam, buspirone, or midazolam (when injected into a vein) (for anxiety or sleep induction)
• zopiclone (for sleep induction)
• reboxetine or venlafaxine (for depression and anxiety)
• aripiprazole, cariprazine, haloperidol, or risperidone (for schizophrenia, bipolar disorder, or other mental health problems)
• galantamine (for Alzheimer's disease)
• guanfacine (for attention deficit hyperactivity disorder)

Medicines for urinary problems

• imidafenacin, fesoterodine, oxybutynin, or solifenacin (for irritated urinary bladder)

Medicines for cancer

• bortezomib, brentuximab vedotin, busulfan, erlotinib, gefitinib, idelalisib, imatinib, nintedanib, panobinostat, ponatinib, ruxolitinib, or sonidegib

Medicines for infections

• ciprofloxacin, clarithromycin, or erythromycin (for bacterial infections)
• delamanid (for tuberculosis)
• artemether-lumefantrine or quinine (for malaria)
• praziquantel (for worms and tapeworms)

Medicines for human immunodeficiency virus (HIV) or hepatitis

• cobicistat, elvitegravir boosted, maraviroc, ritonavir, darunavir boosted with ritonavir, fosamprenavir boosted with ritonavir, indinavir, or saquinavir (for HIV)
• glecaprevir/pibrentasvir (for hepatitis)

Medicines used after organ transplantation

• cyclosporine or tacrolimus

Medicines for benign prostatic hyperplasia

• dutasteride

Medicines for lung problems, allergies, or inflammatory conditions

• bilastine or rupatadine (for allergies)
• methylprednisolone or dexamethasone (oral or injectable medicines for asthma, allergies, or inflammatory conditions)
• budesonide or fluticasone (for asthma, allergies)

Medicines for erection and ejaculation problems

• sildenafil (for erectile dysfunction)

Medicines for pain

• alfentanil, buprenorphine, oxycodone, or sufentanil (for pain)
• meloxicam (for inflammation and joint pain)

Other medicines that contain:

• alitretinoin (oral) (for eczema)
• cabergoline (for Parkinson's disease)
• cannabis-based products, including medicines (for nausea and vomiting or muscle spasms in patients with multiple sclerosis)
• cinacalcet (for excess parathyroid activity)
• dienogest or ulipristal (contraceptives)
• eliglustat (for Gaucher's disease) when used in patients who cannot break down certain medicines in the body
• ivacaftor (for cystic fibrosis)
• methadone (for drug addiction)
• repaglinide or saxagliptin (for diabetes)

This list is not complete, so you should inform your doctor if you are taking or plan to take any of these medicines or any other medicine, so that the necessary measures can be taken.

There should be enough stomach acidity to ensure the absorption of Itraconazol Alter capsules. Therefore, medicines that neutralize stomach acidity should be used at least 2 hours before taking itraconazole or used after 2 hours of taking this medicine. For the same reason, if you are taking medicines that regulate stomach acid production, take Itraconazol Alter with a cola drink (see section 3 "How to take Itraconazol Alter").

In case of doubt, consult your doctor or pharmacist.

Taking Itraconazol Alter with food and drinks

Take this medicine immediately after finishing one of the main meals.

If you are taking any medicine that regulates stomach acid production, it is recommended to take this medicine with a cola drink.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Itraconazol Alter will not be used in case of pregnancy.

If you are of childbearing age and may become pregnant, consult your doctor. You should use effective contraceptives to ensure you do not become pregnant while taking the medicine. Because Itraconazol Alter can stay in the body for a long time, you should extend contraceptive measures until the next menstrual period after finishing treatment with this medicine. (See section 2 "Do not take Itraconazol Alter").

Breastfeeding

If you are breastfeeding, consult your doctor before taking Itraconazol Alter, as small amounts of the medicine may be present in breast milk.

Driving and using machines

Itraconazol Alter can sometimes cause dizziness, blurred or double vision, or hearing loss. If you experience any of these symptoms, do not drive or operate machinery.

Itraconazol Alter contains sucrose

This medicine contains sucrose. If your doctor has told you that you have an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Itraconazol Alter

Follow the administration instructions of Itraconazol Alter exactly as indicated by your doctor. Consult your doctor or pharmacist if you have any doubts. Remember to take your medication.

Your doctor will indicate the duration of your treatment with this medication. Do not suspend treatment beforehand. If you think the action of the medication is too strong or weak, inform your doctor or pharmacist.

You should take Itraconazol Alter immediately after meals, as it is better absorbed. Swallow the capsules whole with a little water. The number of capsules you should take and for how long depends on the type of fungus and the location of the infection. Your doctor will tell you exactly how much itraconazol you should take.

There must be sufficient acidity in the stomach to ensure the absorption of this medication. Therefore, medications that neutralize stomach acidity should be used after two hours of taking this medication or taken two hours before taking Itraconazol Alter capsules. For the same reason, if you are taking medications that regulate stomach acid production, take Itraconazol Alter with a cola drink.

The following doses are the most frequent:

• Nail infections: depending on your personal needs, your doctor will opt for continuous or pulsatile treatment.

• Continuous treatment for foot nail infections:

• Pulsatile treatment for nails:

It consists of two capsules twice a day for 1 week; then stop taking itraconazol capsules for 3 weeks. Then the cycle is repeated, once for hand nails and twice for foot nails (with or without nail infection). (See the following table)

In skin infections, the lesions will disappear a few weeks after finishing treatment. This is characteristic of fungal spots: the medication eliminates the fungus itself, but the lesion does not disappear until new skin grows.

Nail lesions will disappear 6 to 9 months after finishing treatment, since the medication only eliminates the fungus itself. The nail has to grow, and this takes several months. Therefore, do not worry if you do not notice improvement during treatment: the medication remains in your nails for several months and fulfills its mission. Therefore, you should stop treatment at the time indicated by your doctor, even if you do not see any improvement.

Internal organ infections:Higher doses and longer treatment periods may be necessary. Always follow your doctor's instructions; they will adapt the treatment to your needs.

Use in Children

Itraconazol capsules should not be used in children. Only in exceptional cases can it be prescribed by a doctor.

If you take more Itraconazol Alter than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist or the Toxicology Information Service, Phone 91 562 04 20, indicating the medication and the amount used.

In case of accidental overdose, your doctor will apply supportive measures. Itraconazol is not eliminated by hemodialysis. No specific antidotes are known.

If you forget to take Itraconazol Alter

If you forget to take the medication, take the next dose that corresponds to you and continue treatment as indicated by your doctor. Do not take a double dose to make up for forgotten doses.

If you interrupt treatment with Itraconazol Alter

Do not interrupt treatment with itraconazol without consulting your doctor, as symptoms of your disease may reappear or worsen.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medications, Itraconazol Alter can produce adverse effects, although not all people suffer from them.

If you consider that any of the adverse effects you suffer from is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

The following adverse effects are mentioned, which have been seen during the commercialization of the medication and clinical trials.

Adverse reactions were classified according to frequency using the following convention:

Very frequent: may affect more than 1 in 10 people

Frequent: may affect up to 1 in 10 people

Uncommon: may affect up to 1 in 100 people

Rare: may affect up to 1 in 1000 people

Very rare: may affect up to 1 in 100 people

Frequency not known: cannot be estimated from available data

• Infections and infestations

Uncommon: sinusitis (irritation and swelling of the nasal sinuses), upper respiratory tract infection, rhinitis (inflammation of the nasal mucosa that runs with watery mucus production and frequent sneezing)

• Blood and lymphatic system disorders

Rare: leukopenia

• Immune system disorders

Uncommon: hypersensitivity and allergic reaction

Rare: anaphylactic reactions (allergic), serum sickness (allergy that appears after injection of some sera and is characterized by the appearance of hives, fluid accumulation, joint pain, fever, and extreme exhaustion), angioedema (swelling due to fluid accumulation that can affect the mouth and upper airways)

• Metabolic and nutritional disorders

Rare: increased triglycerides

• Nervous system disorders

Frequent: headache

Rare: tremor, tingling sensation in the extremities (paresthesia), decreased sensitivity (hypoesthesia), unpleasant taste (bad taste in the mouth)

• Eye disorders

Rare: visual disturbances (including blurred vision and double vision)

• Ear and labyrinth disorders

Rare: permanent or transient hearing loss, subjective sensation of noises in the ear

• Cardiac disorders

Rare: congestive heart failure

• Respiratory, thoracic, and mediastinal disorders

Rare: shortness of breath, difficulty breathing (dyspnea)

• Gastrointestinal disorders

Frequent: abdominal pain, nausea

Uncommon: vomiting, discomfort associated with eating, diarrhea and constipation, gas accumulation in the intestine (flatulence)

Rare: pancreatitis

• Hepatobiliary disorders

Uncommon: abnormal liver function

Rare: elevated bilirubin levels in blood (hyperbilirubinemia), severe hepatotoxicity (including cases of acute liver failure)

• Skin and subcutaneous tissue disorders

Uncommon: urticaria, rash, itching

Rare: toxic epidermal necrolysis (severe skin disease characterized by skin rash and the appearance of blisters and scales), Stevens-Johnson syndrome (severe skin, mucous membrane, and eye erythema), a severe skin disorder (widespread rash with skin peeling and blisters in the mouth, eyes, and genitals, or rash with small pustules or blisters), erythema multiforme (skin disease characterized by the appearance of vesicles, blisters, etc.), exfoliative dermatitis (skin disease characterized by skin peeling), leukocytoclastic vasculitis (inflammation of the blood vessel wall), alopecia (hair loss), photosensitivity (exaggerated skin response to sunlight)

• Renal and urinary disorders

Rare: increased urination frequency

• Reproductive system and breast disorders

Uncommon: menstrual disorders

Rare: erectile dysfunction

• General disorders and administration site conditions

Rare: edema (fluid accumulation)

Investigations

Rare: increased creatine phosphokinase in blood (parameter that measures liver function)

Description of certain adverse effects

The following adverse effects associated with itraconazol are mentioned, which were reported in clinical trials of itraconazol oral and/or intravenous solution, except for the adverse effect "inflammation at the injection site" since this effect is specific to the injection route.

Blood and lymphatic system disorders: granulocytopenia, thrombocytopenia (decrease in some blood cells)

Immune system disorders: anaphylactoid reaction

Metabolic and nutritional disorders: hyperglycemia (increased sugar in blood), hyperkalemia (increased potassium in blood), hypokalemia (decreased potassium in blood), hypomagnesemia (decreased magnesium in blood)

Psychiatric disorders: feeling of confusion or disorientation

Nervous system disorders: peripheral neuropathy (peripheral nerve damage with tingling, numbness, or weakness in the extremities), dizziness, somnolence

Cardiac disorders: heart failure, left ventricular failure, tachycardia (rapid heart rate)

Vascular disorders: high blood pressure (hypertension), low blood pressure (hypotension)

Respiratory, thoracic, and mediastinal disorders: pulmonary edema, hoarseness, cough

Gastrointestinal disorders: gastrointestinal disorder

Hepatobiliary disorders: liver failure, hepatitis, jaundice (yellowing of the skin, eyes, mucous membranes, and secretions)

Skin and subcutaneous tissue disorders: erythematous rash (red skin rash), excessive sweating

Musculoskeletal and connective tissue disorders: muscle pain or weakness (myalgia), joint pain (arthralgia)

Renal and urinary disorders: renal failure, urinary incontinence (loss of urine)

General disorders and administration site conditions: excessive fluid accumulation in body tissues (generalized edema), fluid accumulation in the face (facial edema), chest pain, fever, pain, fatigue, chills

Investigations: increased alanine aminotransferase, increased aspartate aminotransferase, increased alkaline phosphatase in blood, increased lactate dehydrogenase in blood, increased urea in blood, increased gamma-glutamyltransferase, increased liver enzymes, abnormal urine analysis

Adverse effects in the pediatric population

Based on data from clinical trials in pediatric patients, the most frequently reported adverse effects were: headache, vomiting, abdominal pain, diarrhea, abnormal liver function, low blood pressure, nausea, and urticaria

In general, the nature of the adverse effects is similar to that observed in adult patients, although the incidence is higher in pediatric patients

If you experience any of these adverse effects, consult your doctor

If you consider that any of the adverse effects you suffer from is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report it directly through the Spanish Pharmacovigilance System for Human Use Medications: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication

5. Conservation of Itraconazol Alter

Keep this medication out of sight and reach of children

Do not use Itraconazol Alter after the expiration date that appears on the packaging. The expiration date is the last day of the month indicated

Do not store above 30°C

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment

6. Package contents and additional information

Composition of Itraconazol Alter

• The active ingredient is itraconazol. Each capsule contains 100 mg of itraconazol
• Other components are:

Sugar spheres (cornstarch and sucrose), poloxamer 188, hypromellose

Capsule shell: indigo carmine (E-132), quinoline yellow (E-104), titanium dioxide (E-171), and gelatin

Appearance of the product and package contents

Itraconazol Alter 100 mg capsules are available in packages of 7, 14, or 100 (clinical package) hard capsules in aluminum/aluminum blisters

Only some package sizes may be marketed

Marketing authorization holder and manufacturer: Marketing authorization holder

Laboratorios Alter, S.A.

C/ Mateo Inurria, 30

28036 Madrid

Spain

Manufacturer

Laboratorios Liconsa, S.A. Avda. Miralcampo, Nº 7, Polígono Industrial Miralcampo

19200 Azuqueca de Henares (Guadalajara)

Spain

Date of the last revision of this prospectus: July 2021

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/