Posaconazole Accord

Package leaflet: Information for the user

Posaconazole Accord 100 mg gastro-resistant tablets

posaconazole
Read all of this leaflet carefully before you start 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Posaconazolo Accord contains a medicine called posaconazole. It belongs to a group of medicines known as "antifungals". It is used to prevent and treat many different types of fungal infections.
This medicine works by killing or stopping the growth of certain types of fungi that can cause infections.
Posaconazolo Accord can be used in adults to treat fungal infections caused by fungi of the Aspergillus family:

• Posaconazolo Accord can be used in adults and children from 2 years of age weighing more than 40 kg to treat the following types of fungal infections: fungal infections caused by fungi of the Aspergillus family that have not improved during treatment with the antifungal medicines amphotericin B or itraconazole, or when treatment with these medicines had to be stopped;
• infections caused by fungi of the Fusarium family that have not improved during treatment with amphotericin B or when treatment with amphotericin B had to be stopped;
• infections caused by fungi leading to conditions known as "chromoblastomycosis" and "mycetoma" that have not improved during treatment with itraconazole or when treatment with itraconazole had to be stopped;
• infections caused by a fungus called Coccidioides that have not improved during treatment with one or more of the following medicines: amphotericin B, itraconazole or fluconazole, or when treatment with these medicines had to be stopped.

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

• patients who have a weakened immune system due to chemotherapy for "acute myeloid leukaemia" (AML) or "myelodysplastic syndromes" (MDS);
• patients receiving "high-dose immunosuppressive therapy" following "haematopoietic stem cell transplantation" (HSCT).

2. What you need to know before taking Posaconazole Accord

Do not take Posaconazole Accord if:

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

Do not take Posaconazole Accord if you have any of the above conditions. If you are unsure,
please consult your doctor or pharmacist before taking Posaconazole Accord.
See below under “Other medicines and Posaconazole Accord” for further information, including
details on other medicines that may interact with Posaconazole Accord.

Warnings and precautions
Talk to your doctor or pharmacist before taking Posaconazole Accord if:

• you have had an allergic reaction to another antifungal medicine such as ketoconazole, fluconazole, itraconazole, or voriconazole.
• you have or have had liver problems. You may need blood tests while taking this medicine.
• you develop severe diarrhoea or vomiting, as these conditions may reduce the effectiveness of this medicine.
• you have an abnormal electrocardiogram (ECG) showing a problem called prolonged QTc interval.
• you have weakness of the heart muscle or heart failure.
• you have a very slow heart rate.
• you have a heart rhythm disorder.
• you have any problem with potassium, magnesium, or calcium levels in your blood.
• you are taking vincristine, vinblastine, or other “vinca alkaloids” (medicines used to treat cancer).
• you are taking venetoclax (a medicine used to treat cancer).

If you have any of the conditions listed above (or if you are unsure), consult your doctor,
pharmacist, or nurse before taking Posaconazole Accord.
If you develop severe diarrhoea or vomiting while taking Posaconazole Accord, contact your
doctor, pharmacist, or nurse immediately, as this may prevent the medicine from working
properly. See section 4 for more information.
During treatment, you should avoid exposure to sunlight. It is important to cover exposed
skin areas with protective clothing and to use sunscreen with a high sun protection factor (SPF),
as increased sensitivity of the skin to UV rays from sunlight may occur.

Children
Posaconazole Accord must not be given to children under 2 years of age.

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

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

• 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 abnormalities)

Posaconazole Accord can increase the levels of these medicines in your blood, which may lead
to very serious changes in heart rhythm.

• any medicine containing “ergot alkaloids” such as ergotamine or dihydroergotamine, used to treat migraine. Posaconazole Accord can increase the levels of these medicines in your blood, which may lead to a severe reduction in blood flow to the fingers or toes and could damage them.
• a “statin” such as simvastatin, atorvastatin, or lovastatin, used to treat high cholesterol levels.
• venetoclax when used at the beginning of treatment for a type of cancer, chronic lymphocytic leukemia (CLL).

Do not take Posaconazole Accord if you have any of the above conditions. If you are unsure,
consult your doctor or pharmacist before taking this medicine.

Other medicines
Check the list of medicines above that must not be taken while you are taking Posaconazole Accord. In addition to the medicines listed above, there are other medicines that carry a risk of heart rhythm disturbances, which may be increased when taken with Posaconazole Accord. Make sure to inform your doctor about all medicines you are taking (with or without a prescription).

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

The following medicines may reduce the effectiveness of Posaconazole Accord by decreasing the amount of Posaconazole Accord in the blood:

• rifabutin and rifampicin (used to treat certain infections). If you are already being treated with rifabutin, you will need a blood test and should be alert for possible side effects of rifabutin.
• phenytoin, carbamazepine, phenobarbital, or primidone (used to treat or prevent seizures).
• efavirenz and fosamprenavir (used to treat HIV infection).
• flucloxacillin (an antibiotic used to treat bacterial infections).

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

• vincristine, vinblastine, and other “vinca alkaloids” (used to treat tumours)
• venetoclax (used to treat cancer)
• ciclosporin (used during or after transplant surgery)
• tacrolimus and sirolimus (used during or after transplant surgery)
• 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 known as tretinoin (used to treat certain blood cancers)

If you have any of the above conditions (or if you are unsure), consult your doctor or
pharmacist before taking Posaconazole Accord.

Pregnancy and breastfeeding
Inform your doctor before taking Posaconazole Accord if you are pregnant or suspect you may be pregnant.
Do not take Posaconazole Accord during pregnancy unless specifically instructed by your doctor.
If you are a woman of childbearing potential, you must use an effective method of contraception while taking this medicine. Contact your doctor immediately if you become pregnant while being treated with Posaconazole Accord.
Do not breastfeed while being treated with Posaconazole Accord, as small amounts may pass into breast milk.

Driving and using machines
While being treated with Posaconazole Accord, you may experience dizziness, drowsiness, or blurred vision, which could affect your ability to drive or operate tools or machinery. If this occurs, do not drive or operate tools or machinery and contact your doctor.

Posaconazole Accord contains sodium
Each tablet contains less than 1 mmol of sodium (23 mg), so this medicine is essentially “sodium-free”.

3. How to take Posaconazole Accord

Do not switch from Posaconazole Accord tablets to other medicines containing posaconazole in
oral suspension without consulting your doctor or pharmacist, as this may result in lack of efficacy or an increased risk of adverse reactions.
Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
How much to take
The usual dose is 300 mg (three 100 mg tablets) twice daily on the first day, followed by 300 mg (three 100 mg tablets) once daily thereafter.
The duration of treatment may depend on the type of infection you have and may be individually adjusted by your doctor. Do not adjust the dose yourself or change the treatment regimen without consulting your doctor.
How to take this medicine

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

If you take more Posaconazole Accord than you should
If you think you may have taken more Posaconazole Accord than you should, inform a doctor or go to the hospital immediately.
If you forget to take Posaconazole Accord

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

If you have any doubts about how to use this medicine, consult 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, diarrhoea
• signs of liver problems, including yellowing of the skin or the whites of the eyes, unusually dark urine or pale stools, unexplained feeling of being unwell, stomach problems, loss of appetite, or unusual tiredness or weakness, increased 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:
Common: these may affect up to 1 in 10 people

• changes in blood salt levels detected in blood tests – signs include feeling confused or weak
• abnormal sensations of the skin, such as numbness, tingling, itching, goosebumps, prickling or burning
• headache
• low levels of potassium in the blood – detected in blood tests
• low levels of magnesium – detected in blood tests
• high blood pressure
• loss of appetite, stomach ache or stomach discomfort, passing wind, dry mouth, altered taste
• heartburn (a burning sensation in the chest rising up to the throat)
• low levels of “neutrophils”, a type of white blood cell (neutropenia) – this may increase the risk of getting infections and can be detected in blood tests
• fever
• feeling weak, dizzy, tired or sleepy
• rash
• itching
• constipation
• rectal discomfort

Uncommon: these may affect up to 1 in 100 people

• anaemia – signs include headache, feeling tired or dizzy, shortness of breath or pale appearance, and low haemoglobin levels detected in blood tests
• low platelet count (thrombocytopenia) detected in blood tests – this may lead to bleeding
• low levels of “leucocytes”, a type of white blood cell (leucopenia) detected in blood tests – this may increase the risk of getting infections
• high levels of “eosinophils”, a type of white blood cell (eosinophilia) – this may occur if you have inflammation
• inflammation of blood vessels
• changes in heart rhythm
• seizures
• nerve damage (neuropathy)
• abnormal heart rhythm – detected on electrocardiogram (ECG), palpitations, slow or fast heartbeat, high or low blood pressure
• low blood pressure
• inflammation of the pancreas (pancreatitis) – this may cause severe stomach pain
• interruption of blood supply and oxygen to the spleen (splenic infarction) – this may cause severe stomach pain
• severe kidney problems – signs include increased or decreased urine production with urine of unusual colour
• high levels of creatinine in the blood – detected in blood tests
• cough, hiccups
• nosebleeds
• severe sharp chest pain during breathing (pleuritic pain)
• swollen lymph nodes (lymphadenopathy)
• reduced sensation, especially of the skin
• tremor
• high or low blood sugar levels
• blurred vision, light sensitivity
• hair loss (alopecia)
• mouth ulcers
• chills, general feeling of being unwell
• pain, back pain or neck pain, pain in arms or legs
• fluid retention (oedema)
• menstrual disorders (abnormal vaginal bleeding)
• inability to sleep (insomnia)
• being completely or partially unable to speak
• swelling of the mouth
• abnormal dreams or difficulty sleeping
• problems with coordination or balance
• inflammation of mucous membranes
• nasal congestion
• difficulty breathing
• chest discomfort
• feeling bloated
• mild to severe nausea, vomiting, cramps and diarrhoea, usually caused by a virus, stomach pain
• belching
• feeling nervous

Rare: these may affect up to 1 in 1,000 people

• pneumonia – signs include shortness of breath and discoloured sputum
• high blood pressure in the blood vessels of the lungs (pulmonary hypertension), which may cause serious damage to the lungs and heart
• blood problems such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including extensive blistering skin rashes and peeling of the skin
• mental problems such as hearing voices or seeing things that are not there
• fainting
• problems thinking or speaking, jerky movements, especially in the hands that you cannot control
• stroke – signs include pain, weakness, numbness or tingling in limbs
• having a dark or blind spot in your field of vision
• heart failure or heart attack which could lead to cardiac arrest and death, changes in heart rhythm with sudden death
• blood clots in the legs (deep vein thrombosis) – signs include severe pain or swelling in the legs
• blood clots in the lungs (pulmonary embolism) – signs include shortness of breath or pain when breathing
• bleeding in the stomach or intestines – signs include vomiting blood or blood in the stools
• blockage in the intestine (intestinal obstruction), especially in the “ileum”. The blockage will prevent the contents of the intestine from passing into the lower part of the intestine – signs include feeling bloated, vomiting, severe constipation, loss of appetite and cramps
• “haemolytic uraemic syndrome” when red blood cells break down (haemolysis), a condition that may occur with or without kidney failure
• “pancytopenia”, a low level of all blood cells (red and white blood cells and platelets) detected in blood tests
• widespread purplish discolouration of the skin (thrombotic thrombocytopenic purpura)
• swelling of the face or tongue
• depression
• double vision
• breast pain
• adrenal gland dysfunction – this may cause weakness, tiredness, loss of appetite, skin discolouration
• pituitary gland dysfunction – this may cause low blood levels of certain hormones affecting the function of male or female sex organs
• changes in hearing
• pseudoaldosteronism, causing high blood pressure with low potassium levels (detected in blood tests)

Not known: frequency cannot be estimated from the available data

• Some patients have also reported feeling confused after taking Posaconazole Accord.
• Skin redness

Tell your doctor, pharmacist or nurse if you notice any of the side effects listed above.
Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Posaconazole Accord

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the blister or packaging after EXP. The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Pack contents and other information

What Posaconazole Accord contains
The active substance in Posaconazole Accord is posaconazole. Each tablet contains 100 mg of
posaconazole.
The other components are: methacrylic acid-ethyl acrylate copolymer (1:1), triethyl citrate (E1505),
xylitol (E967), hypromellose (E463), propyl gallate (E310), microcrystalline cellulose (E460),
anhydrous colloidal silica, sodium croscarmellose, sodium stearoyl fumarate, polyvinyl alcohol, titanium
dioxide (E171), macrogol, talc (E553b), yellow iron oxide (E172).
Description of the appearance of Posaconazole Accord and pack contents
The gastro-resistant tablets of Posaconazole Accord are yellow, capsule-shaped, approximately 17.5 mm long and 6.7 mm wide, with "100P" printed on one side and smooth on the other. They are packaged in blisters or divisible unit-dose blisters, in cartons containing 24 or 96 tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona s/n,
Edifici Est, 6th floor, Barcelona,
08039 Barcelona, Spain
Manufacturer
Delorbis Pharmaceuticals Ltd.
17, Athinon Street
Ergates Industrial Area
2643 Nicosia
Cyprus
Laboratori Fundacio Dau
C/ C, 12-14 Pol. Ind. Zona Franca,
Barcelona, 08040, Spain
Accord Healthcare B.V.,
Winthontlaan 200,
3526 KV Utrecht,
The 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
For any information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:
AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT /
NL / NO / PL / PT / RO / SE / SI / SK
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64
EL
Win Medica Α.Ε.
Tel: +30 210 74 88 821
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.