POSACONAZOLE ACCORD 100 mg GASTRO-RESISTANT TABLETS

Introduction

Package Leaflet: Information for the User

Posaconazol Accord 100 mg gastro-resistant tablets EFG

Posaconazol

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, pharmacist, or nurse.
• 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 experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this package leaflet. See section 4.

Contents of the package leaflet

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

1. What is Posaconazol Accord and what is it used for

Posaconazol Accord contains a medicine called posaconazole, which belongs to a group of medicines called "antifungals". It is used to prevent and treat many different fungal infections.

This medicine works by killing or stopping the growth of some types of fungi that can cause infections.

Posaconazol Accord can be used in adults to treat fungal infections caused by fungi of the Aspergillusfamily:

Posaconazol Accord can be used in adults and children from 2 years of age and weighing more than 40 kg to treat the following types of fungal infections:

• infections caused by fungi of the Aspergillusfamily that have not improved during treatment with the antifungal medicines amphotericin B or itraconazole, or when treatment with these medicines has had to be stopped;
• infections caused by fungi of the Fusariumfamily that have not improved during treatment with amphotericin B or when treatment with amphotericin B has had to be stopped;
• infections caused by fungi that cause diseases known as "chromoblastomycosis" and "mycetoma" that have not improved during treatment with itraconazole or when treatment with itraconazole has had to be stopped;
• infections caused by a fungus called Coccidioidesthat have not improved during treatment with one or more medicines, amphotericin B, itraconazole, or fluconazole, or when treatment with these medicines has had to be stopped.

This medicine can also be used to prevent fungal infections in adults and children from 2 years of age and weighing more than 40 kg who are at high risk of getting a fungal infection, such as:

• patients who have a weakened immune system as a result of having received chemotherapy for "acute myelogenous leukemia" (AML) or "myelodysplastic syndromes" (MDS)
• patients who are receiving "high-dose immunosuppressive treatment" after a "hematopoietic stem cell transplant" (HSCT).

2. What you need to know before you take Posaconazol Accord

Do not take Posaconazol Accord if:

• you are allergic to posaconazole or any of the other ingredients of this medicine (listed in section 6).
• you are taking: terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, any medicine that contains "ergot alkaloids", such as ergotamine or dihydroergotamine, or a "statin", such as simvastatin, atorvastatin, or lovastatin.
• you have just started taking venetoclax or your venetoclax dose is being slowly increased for the treatment of chronic lymphocytic leukemia (CLL).

Do not take Posaconazol Accord if you are in any of the above situations. If in doubt, consult your doctor or pharmacist before taking Posaconazol Accord.

See the section "Taking Posaconazol Accord with other medicines" later for more information, including information about other medicines that may interact with Posaconazol Accord.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Posaconazol Accord if you:

• have had an allergic reaction to another antifungal medicine, such as ketoconazole, fluconazole, itraconazole, or voriconazole.
• have or have had liver problems. You may need to have blood tests while taking this medicine.
• develop severe diarrhea or vomiting, as these situations can limit the effectiveness of this medicine.
• have a heart rhythm problem (ECG) that shows a problem called QTc interval prolongation.
• have weakness of the heart muscle or heart failure.
• have a very slow heart rate.
• have any heart rhythm problems.
• have any problems with potassium, magnesium, or calcium levels in your blood.
• are taking vincristine, vinblastine, and other "vinca alkaloids" (medicines used to treat cancer).
• are taking venetoclax (a medicine used to treat cancer).

If you are in any of the above situations (or in doubt), consult your doctor, pharmacist, or nurse before taking Posaconazol Accord.

If you develop severe diarrhea or vomiting while taking Posaconazol Accord, consult your doctor, pharmacist, or nurse immediately, as this situation can prevent the medicine from working properly. For more information, see section 4.

Children

Do not give Posaconazol Accord to children under 2 years of age.

Taking Posaconazol Accord with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Do not take Posaconazol Accord if you are taking any of the following medicines:

• terfenadine (used to treat allergies)
• astemizole (used to treat allergies)
• cisapride (used to treat stomach problems)
• pimozide (used to treat symptoms of Tourette's syndrome and mental illnesses)
• halofantrine (used to treat malaria)
• quinidine (used to treat heart rhythm problems).

Posaconazol Accord may increase the amount of these medicines in your blood, which could cause serious changes in your heart rhythm.

• any medicine that contains "ergot alkaloids", such as ergotamine or dihydroergotamine, used to treat migraines. Posaconazol Accord may increase the amount of these medicines in your blood, which could cause a serious decrease in blood flow to your fingers or toes and damage them.
• a "statin", such as simvastatin, atorvastatin, or lovastatin, used to treat high cholesterol levels.
• venetoclax when used at the start of treatment for a type of cancer, chronic lymphocytic leukemia (CLL).

Do not take Posaconazol Accord if you are in any of the above situations. If in doubt, consult your doctor or pharmacist before taking this medicine.

Other medicines

Consult the list provided earlier with the medicines that you should not use while taking Posaconazol Accord. In addition to the medicines mentioned earlier, there are other medicines that may increase the risk of heart rhythm problems, which may be greater when taken with Posaconazol Accord. Make sure to inform your doctor of all the medicines you are taking (with or without a prescription).

Some medicines may increase the risk of side effects of Posaconazol Accord by increasing the amount of Posaconazol Accord in your blood.

The following medicines may decrease the effectiveness of Posaconazol Accord by reducing its levels in your blood:

• rifabutin and rifampicin (used to treat certain infections). If you are already taking rifabutin, you will need to have a blood test, as well as be aware of some possible side effects of rifabutin.
• phenytoin, carbamazepine, phenobarbital, or primidone (used to treat or prevent seizures).

• efavirenz and fosamprenavir, used to treat HIV infection.

Posaconazol Accord may increase the risk of side effects of other medicines by increasing their levels in your blood. These medicines include:

• vincristine, vinblastine, and other "vinca alkaloids" (used to treat cancer)
• venetoclax (used to treat cancer)
• cyclosporine (used during or after transplants)
• tacrolimus and sirolimus (used during or after transplants)
• rifabutin (used to treat certain infections)
• medicines used to treat HIV called protease inhibitors (including lopinavir and atazanavir, which are given with ritonavir)
• midazolam, triazolam, alprazolam, or other "benzodiazepines" (used as sedatives or muscle relaxants)
• diltiazem, verapamil, nifedipine, nisoldipine, or other "calcium channel blockers" (used to treat high blood pressure)
• digoxin (used to treat heart failure)
• glipizide or other "sulfonylureas" (used to treat high blood sugar levels).
• all-trans retinoic acid (ATRA), also called tretinoin (used to treat some blood cancers).

If you are in any of the above situations (or in doubt), consult your doctor or pharmacist before taking Posaconazol Accord.

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or think you may be pregnant before you start taking Posaconazol Accord.

Do not take Posaconazol Accord if you are pregnant, unless your doctor tells you to.

If you are of childbearing age, you should use effective contraceptive measures while taking this medicine. If you become pregnant while taking Posaconazol Accord, contact your doctor immediately.

Do not breastfeed while taking Posaconazol Accord, as it may pass into breast milk in small amounts.

Driving and using machines

You may feel dizzy, sleepy, or have blurred vision while taking Posaconazol Accord, which may affect your ability to drive or use tools or machines. If this happens, do not drive or use any tools or machines and contact your doctor.

Posaconazol Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which is essentially "sodium-free".

3. How to take Posaconazol Accord

Do not switch between Posaconazol Accord tablets and Posaconazol Accord oral suspension without consulting your doctor or pharmacist, as this may lead to a lack of effectiveness or increase the risk of adverse reactions.

Follow the instructions for taking this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist again.

How much to take

The usual dose is 300 mg (three 100 mg tablets) twice a day on the first day, and then 300 mg (three 100 mg tablets) once a day.

The duration of treatment may depend on the type of infection you have and may be adjusted individually for you by your doctor. Do not change your dose yourself before consulting your doctor, or change your treatment regimen.

How to take this medicine

• Swallow the tablet whole with water.
• Do not crush, chew, break, or dissolve the tablet.
• The tablets can be taken with or without food.

If you take more Posaconazol Accord than you should

If you think you may have taken too much Posaconazol Accord, contact your doctor or go to the hospital immediately.

If you forget to take Posaconazol Accord

• If you miss a dose, take it as soon as you remember.
• However, if it is almost time for your next dose, do not take the missed dose and continue with your regular dosing schedule.
• Do not take a double dose to make up for a missed dose.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious Side Effects

Tell your doctor, pharmacist, or nurse immediately if you notice any of the following serious side effects; you may need urgent medical treatment:

• nausea or vomiting (feeling or being sick), diarrhea
• signs of liver problems, which include yellowing of the skin or the whites of the eyes, unusually dark urine or pale stools, feeling sick without an apparent reason, stomach problems, loss of appetite, or unusual tiredness or weakness, an increase in liver enzymes detected in blood tests
• allergic reaction

Other Side Effects

Tell your doctor, pharmacist, or nurse if you notice any of the following side effects:

Frequent: the following may affect up to 1 in 10 patients

• a change in blood salt levels detected in blood tests, whose signs include a feeling of confusion or weakness
• abnormal sensations in the skin, such as numbness, tingling, itching, crawling, pinching, or burning
• headache
• low potassium levels, detected in blood tests
• low magnesium levels, detected in blood tests
• high blood pressure
• loss of appetite, stomach pain, or stomach discomfort, flatulence, dry mouth, changes in taste
• heartburn (a burning sensation in the chest that rises to the throat)
• low levels of "neutrophils," a type of white blood cell (neutropenia), which can make you more prone to infections and are detected in blood tests
• fever
• feeling of weakness, dizziness, tiredness, or drowsiness
• rash
• itching
• constipation
• rectal discomfort

Infrequent: the following may affect up to 1 in 100 patients

• anemia, whose signs include headaches, feeling tired or dizzy, difficult breathing, or paleness and low hemoglobin levels detected in blood tests
• low platelet levels (thrombocytopenia), detected in blood tests. This can cause bleeding
• low levels of "leukocytes," a type of white blood cell (leukopenia), detected in blood tests. This can make you more susceptible to infections
• high levels of "eosinophils," a type of white blood cell (eosinophilia). This can appear if you have an inflammatory process
• inflammation of blood vessels
• heart rhythm problems
• seizures (convulsions)
• nerve damage (neuropathy)
• abnormal heart rhythm, detected in an electrocardiogram (ECG), palpitations, slow or fast heartbeat, high or low blood pressure
• low blood pressure
• inflammation of the pancreas (pancreatitis). This can cause severe stomach pain
• interruption of oxygen supply to the spleen (splenic infarction), which can cause severe stomach pain
• severe kidney problems, whose signs include increased or decreased urination with urine that has a different color than usual
• high blood creatinine levels, detected in blood tests
• cough, hiccups
• nosebleeds
• sharp and intense chest pain when breathing (pleuritic pain)
• inflammation of the lymph nodes (lymphadenopathy)
• decreased sensitivity, especially in the skin
• tremors
• high or low blood sugar levels
• blurred vision, sensitivity to light
• hair loss (alopecia)
• mouth ulcers
• chills, feeling of discomfort
• pain, back or neck pain, pain in arms or legs
• fluid retention (edema)
• menstrual problems (abnormal vaginal bleeding)
• inability to sleep (insomnia)
• inability to speak totally or partially
• mouth swelling
• abnormal dreams or sleep problems
• coordination or balance problems
• mucous membrane inflammation
• nasal congestion
• breathing difficulties
• chest discomfort
• feeling bloated
• nausea, vomiting, cramps, and diarrhea from mild to severe, usually caused by a virus, stomach pain
• belching
• feeling of restlessness

Rare: the following may affect up to 1 in 1,000 patients

• pneumonia, whose signs include shortness of breath and production of discolored phlegm
• high blood pressure in the blood vessels of the lungs (pulmonary hypertension), which can cause serious damage to the lungs and heart
• blood problems such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including widespread skin rash with blisters and skin peeling
• mental problems, such as hearing voices or seeing things that are not there
• fainting
• problems thinking or speaking, sudden movements, especially in your hands, that you cannot control
• stroke, whose signs include pain, weakness, numbness, or tingling in the limbs
• presence of a blind spot or dark spot in the field of vision
• heart failure or heart attack, which can cause cardiac arrest and death, heart rhythm problems with sudden death
• blood clots in the legs (deep vein thrombosis), whose signs include intense pain or swelling of the legs
• blood clots in the lungs (pulmonary embolism), whose signs include shortness of breath or pain when breathing
• bleeding in the stomach or intestine, whose signs include vomiting blood or blood in the stool
• blockage of the intestine (intestinal obstruction), especially of the "ileum." This blockage prevents the contents of the intestine from passing through the colon and whose signs include a feeling of bloating, vomiting, severe constipation, loss of appetite, and cramps
• "hemolytic uremic syndrome" that appears when there is destruction of red blood cells (hemolysis), which can occur with or without kidney failure
• "pancytopenia," low levels of all blood cells (red, white, and platelets), detected in blood tests
• large purple spots on the skin (thrombocytopenic purpura)
• inflammation of the face or tongue
• depression
• double vision
• breast pain
• inadequate functioning of the adrenal glands, which can cause weakness, tiredness, loss of appetite, skin discoloration
• inadequate functioning of the pituitary gland, which can cause low blood levels of some hormones that affect the function of male or female sexual organs

• hearing problems
• pseudoaldosteronism, which causes high blood pressure with low potassium levels (appears in blood tests)

Frequency not known: cannot be estimated from the available data

• some patients have also reported feeling confused after taking Posaconazol Accord.

Tell your doctor, pharmacist, or nurse if you experience any of the side effects described above.

Reporting Side Effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Posaconazol Accord

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date that appears on the blister after CAD. The expiration date is the last day of the month indicated.
• No special storage conditions are required.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Posaconazol Accord

The active ingredient is posaconazole. Each tablet contains 100 mg of posaconazole.

The other ingredients are methacrylic acid-ethyl acrylate copolymer (1:1), triethyl citrate (E1505), xylitol (E967), hydroxypropyl cellulose (E463), propyl gallate (E310), microcrystalline cellulose (E460), anhydrous colloidal silica, sodium croscarmellose, sodium stearyl fumarate, polyvinyl alcohol, titanium dioxide (E171), macrogol, talc (E553b), yellow iron oxide (E172).

Appearance of the Product and Package Contents

Posaconazol Accord gastro-resistant tablets have a yellow coating, are capsule-shaped, approximately 17.5 mm long and 6.7 mm wide, are marked with the digits "100" on one side while the other side is smooth, and are packaged in blisters or perforated blisters with single doses in boxes of 24 or 96 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6a planta, Barcelona,

08039 Barcelona, Spain

Manufacturer

Delorbis Pharmaceuticals Limited

Ergates Industrial Area

Athinon 17 V, Ergates

Nicosia, 2643

Cyprus

Laboratori Fundacio Dau

C/ C, 12-14 Pol. Ind. Zona Franca,

Barcelona, 08040, Spain

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola, PLA 3000

Malta

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice,

Poland

Date of the Last Revision of this Leaflet: {MM/AAAA}

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.