Patient Information Leaflet

Conferoport 0.5 mg prolonged-release hard capsules EFG

Conferoport 1 mg prolonged-release hard capsules EFG

Conferoport 2 mg prolonged-release hard capsules

Conferoport 3 mg prolonged-release hard capsules EFG

Conferoport 5 mg prolonged-release hard capsules EFG

tacrolimus

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

• Keep this leaflet, as 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 they have similar symptoms to you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet

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

Conferoport contains the active ingredient tacrolimus. It is an immunosuppressant. After an organ transplant (liver, kidney), your body's immune system will try to reject the new organ. Conferoport is used to control your body's immune response, allowing you to accept the transplanted organ.

You may also receive Conferoport to treat a rejection that is occurring in your liver, kidney, heart, or other transplanted organ, when any previous treatment you were following cannot control this immune response after your transplant.

Conferoport is used in adults.

Do not take Conferoport

• if you are allergic (hypersensitive) to tacrolimusor to any of the other components ofthis medicine (listed in section 6),
• if you are allergic to sirolimus or to any macrolide antibiotic (e.g., erythromycin, clarithromycin, josamycin),
• if you are allergic to peanuts or to soy.

Warnings and precautions

Conferoport capsules and tacrolimus immediate-release capsules both contain the active ingredient tacrolimus. However, Conferoport is taken once a day, while tacrolimus immediate-release capsules are taken twice a day.This is because Conferoport capsules allow for a prolonged release (slower release over a longer period of time) of tacrolimus. Conferoport and tacrolimus immediate-release capsules are not interchangeable.

Inform your doctor or pharmacist before taking Conferoport:

• if you are taking any of the medicines listed in “Other medicines and Conferoport”,
• if you have or have had liver problems,
• if you have had diarrhea for more than a day,
• if you have severe abdominal pain accompanied or not by other symptoms, such as chills, fever,nausea or vomiting,
• if you have an abnormal heart rhythm called “prolongation of the QT interval”,
• if you have or have had small blood vessel damage, known as microangiopathic hemolytic anemia/thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Inform your doctor if you develop fever, skin hemorrhages (which may appear as red spots), inexplicable fatigue, confusion, yellowing of the skin or eyes, decreased urine output, vision loss, and seizures (see section 4). When tacrolimus is taken with sirolimus or everolimus, the risk of these symptoms may increase.

Please avoid taking any herbal preparations, e.g., St. John's Wort (Hypericum perforatum), as this may affect the efficacy and dose of tacrolimus you need to receive. If you have any doubts, please consult your doctor before taking any herbal preparations.

Inform your doctor immediately if during treatment you experience:

• vision problems such as blurred vision, changes in color vision, difficulty seeing details, or reduced visual field.

Your doctor may need to adjust your Conferoport dose.

You should maintain regular contact with your doctor. Occasionally, to establish the appropriate dose of Conferoport, your doctor may need to perform blood and urine tests, cardiac tests, and eye tests.

You should limit your exposure to sunlight and UV (ultraviolet) light while taking Conferoport. This is because immunosuppressants may increase the risk of skin cancer. Wear protective clothing and use a high-factor sunscreen.

Precautions for handling:

During preparation, avoid contact with any part of the body, such as the skin or eyes, as well as breathing near the injection solutions, powder, or granules contained in tacrolimus products. If such contact occurs, wash the skin and eyes.

Children and adolescents

Conferoport is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Conferoport

Inform your doctor or pharmacist if you are taking or have taken recentlyor may need to takeany other medicine, including those purchased without a prescription and herbal preparations.

Conferoport should not be used with cyclosporin (another medicine used to prevent organ transplant rejection).

If you need to visit a doctor other than your transplant specialist, tell the doctor that you are taking tacrolimus. Your doctor may need to consult with your transplant specialist if you need to take another medicine that may increase or decrease your tacrolimus blood levels.

Tacrolimus blood levels may be affected by other medicines you are taking, and blood levels of other medicines may be affected by tacrolimus administration, which may require interruption, increase, or decrease of the Conferoport dose.

Some patients have experienced increased tacrolimus blood levels while taking other medicines. This could cause severe adverse effects, such as kidney problems, nervous system problems, and cardiac rhythm disorders (see section 4).

The effect on Conferoport blood levels can occur very soon after starting another medicine, so it may be necessary to monitor Conferoport blood levels frequently and continuously during the first days of use of another medicine and frequently while continuing its use. Some other medicines may cause tacrolimus blood levels to decrease, which may increase the risk of organ transplant rejection. In particular, you should inform your doctor if you are taking or have taken recently:

• antifungals and antibiotics, especially macrolide antibiotics, used to treat infections, e.g., ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, clotrimazole, isavuconazole, miconazole, caspofungin, telithromycin, erythromycin, clarithromycin, josamycin, azithromycin, rifampicin, rifabutin, isoniazid, and flucloxacillin,
• letermovir, used to prevent diseases caused by CMV (human cytomegalovirus),
• protease inhibitors for HIV (e.g., ritonavir, nelfinavir, saquinavir), the pharmacopotentiator cobicistat, and HIV combination tablets or non-nucleoside reverse transcriptase inhibitors for HIV (efavirenz, etravirine, nevirapine), used to treat HIV infection,
• protease inhibitors for HCV (e.g., telaprevir, boceprevir, and the combination ombitasvir/paritaprevir/ritonavir, with or without dasabuvir), elbasvir/grazoprevir, and glecaprevir/pibrentasvir, used to treat HCV infection,
• nilotinib, imatinib, idelalisib, ceritinib, crizotinib, apalutamide, enzalutamide, or mitotane (used to treat certain types of cancer),
• acid mycophenolate, used to suppress the immune system as a transplant rejection prevention,
• medicines for stomach ulcers and acid reflux (e.g., omeprazole, lansoprazole, or cimetidine),
• antiemetics, used to treat nausea and vomiting (e.g., metoclopramide),
• cisapride or antacids containing magnesium hydroxide and aluminum, used to treat acid reflux,
• oral contraceptives or other hormone treatments with ethinylestradiol, hormone treatments with danazol,
• medicines used to treat high blood pressure or heart problems (e.g., nifedipine, nicardipine, diltiazem, and verapamil),
• antiarrhythmic medicines (amiodarone) used to control irregular heartbeats,
• statins used to treat high cholesterol and triglycerides,
• carbamazepine, phenytoin, or phenobarbital, used to treat epilepsy,
• corticosteroids prednisolone or methylprednisolone, used to treat inflammation or suppress the immune system (e.g., transplant rejection),
• nefazodone, used to treat depression,
• herbal preparations containing St. John's Wort (Hypericum perforatum) or Schisandra sphenanthera extracts,
• metamizole, used to treat pain and fever,
• cannabidiol (its use includes, among others, the treatment of epilepsy).

Inform your doctor if you are receiving treatment for hepatitis C. Hepatitis C treatment may change your liver function and affect tacrolimus blood levels. Tacrolimus blood levels may decrease or increase depending on the hepatitis C medicines prescribed. Your doctor may need to closely monitor tacrolimus blood levels and make necessary adjustments to the Conferoport dose after starting hepatitis C treatment.

Inform your doctor if you are taking or need to take ibuprofen (used to treat fever, inflammation, and pain), antibiotics (cotrimoxazole, vancomycin, or aminoglycoside antibiotics such as gentamicin), amphotericin B (used to treat fungal infections), or antivirals (used to treat viral infections, e.g., aciclovir, ganciclovir, cidofovir, foscarnet). These medicines may worsen kidney or nervous system problems when taken with Conferoport.

Inform your doctor if you are taking sirolimus or everolimus. When tacrolimus is taken with sirolimus or everolimus, the risk of microangiopathic hemolytic anemia, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome may increase (see section 4).

Your doctor also needs to know if you are taking potassium supplements or certain diuretics used to treat heart failure, hypertension, and nephropathy (e.g., amiloride, triamterene, or spironolactone), or trimethoprim and cotrimoxazole antibiotics that may increase potassium levels in your blood ,nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen) used to treat fever, inflammation, and pain, anticoagulants (which prevent blood clotting), or oral diabetes medications while taking Conferoport.

If you plan to be vaccinated, consult your doctor.

Conferoport with food and drinks

Avoid grapefruit (also in juice) while taking Conferoport, as it may affect your blood levels.

Pregnancy and breastfeeding

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

Conferoport passes into breast milk. Therefore, do not breastfeed while taking Conferoport.

Driving and operating machinery

Do not drive and do not operate tools or machines if you feel dizzy or drowsy, or havedifficulty seeing clearly after taking Conferoport. These effects are more frequent if you also take alcohol.

Capsules of 0.5 mg and 2 mg

Conferoport contains lactose and azo dyes, which contain sodium and soy

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

This medicine may cause allergic reactions because it contains yellow orange S (E 110) and red allura AC (E 129) and tartrazine (E 102).

This medicine contains less than 1 mmol of sodium (23 mg) per prolonged-release hard capsule; this is essentially “sodium-free”.

The printing ink used in Conferoport capsules contains soy lecithin. If you are allergic to peanuts or soy, do not take this medicine.

Capsules of 1 mg, 3 mg, and 5 mg

Conferoport contains lactose and azo dyes, which contain sodium and soy

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

This medicine may cause allergic reactions because it contains yellow orange S (E 110) and red allura AC (E 129).

This medicine contains less than 1 mmol of sodium (23 mg ) per prolonged-release hard capsule; this is essentially “sodium-free”.

The printing ink used in Conferoport capsules contains soy lecithin. If you are allergic to peanuts or soy, do not take this medicine.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again. This medication should only be prescribed by a doctor with experience in treating patients with transplants.

Make sure you receive the same medication with tacrolimus every time you pick up your prescription, unless your transplant specialist has agreed to switch to a different tacrolimus medication. This medication should be taken once a day. If the appearance of this medication is not the same as always, or if the dosing instructions have changed, consult your doctor or pharmacist as soon as possible to ensure you have the correct medication.

The initial dose to prevent rejection of your transplanted organ will be set by your doctor, calculated according to your body weight. The initial daily doses immediately after the transplant will generally be within the range of 0.10 – 0.30 mg per kg of body weight and per day, depending on the transplanted organ. To treat rejection, these same doses may be used.

Your dose will depend on your general condition and any other immunosuppressive medication you may be taking.

After starting your treatment with Conferoport, your doctor will perform frequent blood tests to determine the correct dose. Later, your doctor will need to perform regular blood tests to determine the correct dose and adjust the dose from time to time. Your doctor will usually reduce your Conferoport dose once your condition has stabilized. Your doctor will tell you exactly how many capsules you should take.

You will need to take Conferoport every day until you no longer need immunosuppression to prevent rejection of your transplanted organ. You should maintain regular contact with your doctor.

Conferoport is taken orally once a day, in the morning. Take Conferoport with an empty stomach or 2 to 3 hours after a meal. Wait at least one hour before the next meal. Take the capsules immediately after removing them from the blister. The capsules should be swallowed whole with a glass of water. Do not swallow the desiccant contained in the aluminum bag.

If you take more Conferoport than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Conferoport

If you have forgotten to take your Conferoport capsules in the morning, take them as soon as possible on the same day. Do not take a double dose the next morning to compensate for the missed doses.

If you interrupt treatment with Conferoport

Stopping your treatment with Conferoport may increase the risk of rejection of your transplanted organ. Do not stop treatment unless your doctor tells you to.

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

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

Conferoport reduces the body's defense mechanisms (immune system), which will not work as well to fight infections. Therefore, if you are taking Conferoport, you will be more prone to infections. Some infections can be severe or fatal and may include infections caused by bacteria, viruses, fungi, parasites, or other infections.

Inform your doctor immediately if you have symptoms of an infection, including:

• Fever, cough, sore throat, feeling weak or generally unwell,
• Memory loss, difficulty thinking, difficulty walking or loss of vision,

These symptoms may be due to a rare and severe brain infection that can be fatal (multifocal progressive leukoencephalopathy or MPA).

Severe effects may occur, including allergic reactions and anaphylaxis. Benign and malignant tumors have been reported after treatment with Conferoport.

Inform your doctor immediately if you suspect you are experiencing any of the following severe side effects:

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

• Gastrointestinal perforation: severe abdominal pain accompanied or not by other symptoms such as chills, fever, nausea, or vomiting.
• Insufficient function of your transplanted organ.
• Blurred vision

Less common severe side effects (may affect up to 1 in 100 people):

• Microangiopathic thrombosis (lesions in smaller blood vessels) including hemolytic uremic syndrome with the following symptoms: low or no urine output (acute kidney failure), extreme fatigue, yellowing of the skin or eyes (jaundice), and abnormal bleeding or bruising and signs of infection.

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

• Purpura thrombocytopenic thrombocytopenia: includes lesions in smaller blood vessels and is characterized by fever and hematomas under the skin that may appear as red spots, with or without extreme fatigue, confusion, yellowing of the skin or eyes (jaundice), with symptoms of acute kidney failure (low or no urine output), loss of vision, and seizures.
• Toxic epidermal necrolysis: erosion and blistering of the skin or mucous membranes, red and swollen skin that may peel off in large areas of the body.
• Blindness.

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

• Stevens-Johnson syndrome: inexplicable generalized skin pain, facial swelling, severe disease with blistering of the skin, mouth, eyes, and genitals, rashes, facial swelling, and skin peeling.
• Torsades de pointes: a change in heart rate that may or may not be accompanied by symptoms such as chest pain (angina), fainting, dizziness, nausea, palpitations (feeling heartbeats), and difficulty breathing.

Severe side effects of unknown frequency (frequency cannot be estimated from available data):

• Oportunist infections (bacterial, fungal, viral, and protozoal): prolonged diarrhea, fever, and sore throat.
• Benign and malignant tumors have been reported after treatment as a result of immunosuppression, including malignant skin cancers and a rare type of cancer that may include skin lesions known as Kaposi's sarcoma. Symptoms include skin changes such as new colors or changes to existing ones, lesions, or lumps
• Severe cases of pure red cell aplasia (a very significant reduction in the number of red blood cells), hemolytic anemia (a decrease in the number of red blood cells due to abnormal rupture accompanied by fatigue), and febrile neutropenia (a decrease in the type of white blood cells that fight infections, accompanied by fever). The exact frequency of these side effects is unknown. You may not have symptoms or, depending on the severity of your condition, you may feel: fatigue, apathy, abnormal paleness of the skin (pallor), difficulty breathing, dizziness, headache, chest pain, and a feeling of coldness in your hands and feet.
• Cases of agranulocytosis (a significant decrease in the number of white blood cells accompanied by mouth sores, fever, and infections). You may not have symptoms or you may feel fever, chills, and sudden sore throat.
• Allergic reactions and anaphylaxis with the following symptoms: sudden itching rash (hives), swelling of hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing) and you may feel like you are going to faint.
• Reversible posterior leukoencephalopathy syndrome (RPLS): headache, confusion, mood changes, seizures, and visual disturbances. These may be signs of a condition known as reversible posterior leukoencephalopathy syndrome, which has been reported in some patients treated with tacrolimus.
• Optic neuropathy (alteration of the optic nerve): vision problems such as blurred vision, changes in color vision, difficulty seeing details, or reduced visual field.

After receiving Conferoport, the following side effects may also occur and may be severe:

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

• Increased blood sugar, diabetes mellitus, increased potassium in the blood.
• Difficulty sleeping.
• Tremors, headache.
• Increased blood pressure.
• Abnormal liver function test results.
• Diarrhea, nausea.
• Renal problems.

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

• Reduction in the number of blood cells (platelets, red blood cells, or white blood cells), increased white blood cell count, changes in red blood cell counts (see blood test results).
• Reduction in magnesium, phosphate, potassium, calcium, or sodium in the blood, fluid overload, increased uric acid or lipids in the blood, decreased appetite, increased blood acidity, other changes in blood electrolytes (see blood test results).
• Anxiety symptoms, confusion, and disorientation, depression, mood changes, nightmares, hallucinations, mental disorders.
• Seizures, altered level of consciousness, tingling and numbness (sometimes painful) in the hands and feet, dizziness, decreased ability to write, nervous system disorders.
• Blurred vision, increased sensitivity to light, eye disorders.
• Tinnitus (ringing in the ears).
• Reduced blood flow in heart vessels, faster heart rate.
• Bleeding, partial or complete blockage of blood vessels, reduced blood pressure.
• Lack of breath, respiratory tissue disorders in the lungs, fluid accumulation around the lungs, pharyngeal inflammation, cough, flu-like symptoms.
• Gastrointestinal problems such as inflammation or ulcers that cause abdominal pain or diarrhea, stomach bleeding, inflammation or ulcers in the mouth, fluid accumulation in the intestines, vomiting, abdominal pain, indigestion, constipation, flatulence (gas), abdominal swelling, loose stools.
• Bile duct disorders, yellowing of the skin due to liver problems, liver tissue damage, and liver inflammation.
• Itching, rash, hair loss, acne, increased sweating.
• Pain in the joints, extremities, back, and feet, muscle spasms.
• Renal insufficiency, reduced urine production, limited or painful urination.
• General weakness, fever, fluid accumulation in the body, pain and discomfort, increased alkaline phosphatase in the blood, weight gain, feeling of altered temperature.

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

• Changes in blood clotting, reduction in the number of all types of blood cells (see blood test results).
• Dehydration, inability to urinate.
• Abnormal blood test results: reduction in proteins or sugar, increased phosphate, increased lactate dehydrogenase enzyme.
• Coma, cerebral hemorrhage, stroke, paralysis, brain disorders, speech and language disorders, memory problems.
• Opacity of the crystalline lens, hearing loss.
• Irregular heartbeat, cardiac arrest, decreased heart function, cardiac muscle disorders, increased heart muscle size, faster heartbeat, abnormal ECG, abnormal heart rate and pulse.
• Thrombosis in a vein of an extremity, shock.
• Difficulty breathing, respiratory tract disorders, asthma.
• Intestinal obstruction, increased blood enzyme amylase, gastroesophageal reflux, delayed stomach emptying.
• Skin inflammation, sunburn-like sensation.
• Joint disorders.
• Menstrual pain and abnormal menstrual bleeding.
• Multi-organ failure, flu-like illness, increased sensitivity to heat and cold, chest pressure sensation, restlessness or abnormal sensation, weight loss.

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

• Small skin bleeding due to blood clots.
• Increased muscle stiffness.
• Hearing loss.
• Fluid accumulation around the heart.
• Acute shortness of breath.
• Pancreatic cyst formation.
• Problems with blood flow in the liver.
• Severe disease with vesicle formation in the skin, mouth, eyes, and genitals; increased hair growth.
• Sedation, falls, chest pressure sensation, decreased mobility, ulcers.

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

• Muscle weakness.
• Abnormal echocardiogram.
• Liver insufficiency.
• Painful urination with blood in the urine.
• Increased body fat.

Reporting side effects

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

Keep this medication out of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears on the carton packaging and on the blister pack after “CAD/EXP”. The expiration date is the last day of the month indicated. Use all capsules within the year following the opening of the aluminum bag and before the expiration date.

Store in the original packaging (aluminum bag) to protect it from light and moisture.

Take the capsule immediately after removing it from the blister pack.

Medicines should not be thrown away through the drains or in the trash. Dispose of the packaging and medicines you no longer need at the Sigre Pointat the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. In this way, you will help protect the environment.

.

• The active ingredient is tacrolimus. Each capsule contains 0.5 mg, 1 mg, 2 mg, 3 mg or 5 mg of tacrolimus (as monohydrate).
• The other components are:

Capule content: ethylcellulose, hypromellose, lactose, magnesium stearate.

Capsule coating:

Capsules of 0.5 mg and 2 mg

Brilliant blue FCP (E133), allura red AC (E129), titanium dioxide (E171), yellow orange S (E110), gelatin, tartrazine (E102).

Capsules of 1 mg and 3 mg

Brilliant blue FCP (E133), allura red AC (E129), titanium dioxide (E171), yellow orange S (E110), gelatin.

Capsules of 5 mg

Brilliant blue FCP (E133), allura red AC (E129), titanium dioxide (E171), yellow orange S (E110), gelatin, erythrosine (E127).

Printing ink

Shellac resin, aluminum lake of allura red AC (E129), aluminum lake of brilliant blue FCP (E133), aluminum lake of yellow orange S (E110), propylene glycol (E1520), soy lecithin, simethicone.

Capsules of 1 mg, 3 mg and 5 mg

See section 2 “Conferoport contains lactose and azo dyes, which contain sodium and soy”.

Capsules of 0.5 mg and 2 mg

See section 2 “Conferoport 0.5 mg contains lactose and azo dyes, which contain sodium and soy.

Appearance of the product and contents of the package

Capsules of 0.5 mg

Size 5 gelatin capsule with a light brown body and a clear yellow cap, printed in black with "0.5 mg", containing white to yellowish powder or compacted powder (length of 10.7 – 11.5 mm).

Capsules of 1 mg

Size 4 gelatin capsule with a light brown body and a white cap, printed in black with "1 mg", containing white to yellowish powder or compacted powder (length of 14.0 – 14.6 mm).

Capsules of 2 mg

Size 3 gelatin capsule with a light brown body and a dark green cap, printed in black with "2 mg", containing white to yellowish powder or compacted powder (length 15.6 – 16.2 mm).

Capsules of 3 mg

Size 2 gelatin capsule with a light brown body and a light orange cap, printed in black with "3 mg", containing white to yellowish powder or compacted powder (length 17.7 – 18.3 mm).

Capsules of 5 mg

Size 0 gelatin capsule with a light brown body and a pink cap, printed in black with "5 mg", containing white to yellowish powder or compacted powder (length 21.4 – 22.0 mm).

PVC/PVDC and aluminum blister with a sealed desiccant in an aluminum bag. The desiccant should not be swallowed.

Package sizes: 30 prolonged-release hard capsules in a blister or perforated single-dose blisters of 30x1 and 60x1 (2x30) [only for 1 mg].

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Responsible manufacturer

Lek Pharmaceuticals, d.d.

Trimlini 2D

9220 Lendava

Slovenia

Last review date of this leaflet: March 2025

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/