Posaconazole AHCL

Package leaflet: Information for the user

Posaconazole AHCL 40 mg/mL oral suspension

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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Posaconazole AHCL is and what it is used for

Posaconazole AHCL contains a medicine called posaconazole. It belongs to a group of medicines called "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.
Posaconazole AHCL may be used in adults to treat the following types of fungal infections when other antifungal medicines have not worked or had to be discontinued:

• 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;
• infections of the mouth or throat (known as "oral thrush") caused by fungi called Candida, when not previously treated.

This medicine may also be used to prevent fungal infections in adults 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 HCl

Do not take Posaconazole HCl 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 HCl if you have any of the conditions listed above. If you are unsure,
consult your doctor or pharmacist before taking Posaconazole HCl.
See below under “Other medicines and Posaconazole HCl” for further information, including
details on other medicines that may interact with Posaconazole HCl.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Posaconazole HCl 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 diarrhea or vomiting, as these conditions may reduce the effectiveness of this medicine.
• you have an abnormal electrocardiogram (ECG) showing a condition called prolonged QTc interval.
• you have weakened heart muscle (heart) 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).

If you have any of the conditions listed above (or if you are unsure), consult your doctor,
pharmacist, or nurse before taking Posaconazole HCl.
If you develop severe diarrhea or vomiting while taking Posaconazole HCl, 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 sun-exposed
areas of skin with protective clothing and use sunscreen with a high sun protection factor (SPF),
as increased sensitivity of the skin to UV rays from sunlight may occur.
Children
Posaconazole HCl oral suspension must not be used in children and adolescents (aged 17 years or younger).
Other medicines and Posaconazole HCl
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not take Posaconazole HCl 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)
• venetoclax when used at the beginning of treatment for a type of cancer, chronic lymphocytic leukemia (CLL).

Posaconazole HCl can increase the amount 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 HCl can increase the amount 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.

Do not take Posaconazole HCl if you have any of the conditions listed above. 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 taking Posaconazole HCl. In addition to the medicines listed above, there are other medicines that carry a risk of heart rhythm disturbances, which may be greater when taken with Posaconazole HCl. Make sure to inform your doctor about all medicines you are taking (with or without prescription).
Some medicines may increase the risk of side effects of Posaconazole HCl by increasing the amount of Posaconazole HCl in the blood.
The following medicines may reduce the effectiveness of Posaconazole HCl by decreasing the amount of Posaconazole HCl 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 pay attention to possible side effects of rifabutin.
• certain medicines used to treat or prevent seizures, including phenytoin, carbamazepine, phenobarbital, or primidone.
• efavirenz and fosamprenavir used to treat HIV infection.
• medicines used to reduce stomach acid such as cimetidine and ranitidine, or omeprazole and similar medicines called proton pump inhibitors.
• flucloxacillin (an antibiotic used against bacterial infections)

Posaconazole HCl may increase the risk of side effects from certain other medicines by increasing the amount of these medicines in the blood. These medicines include:

• vincristine, vinblastine, and other "vinca alkaloids" (used to treat tumors)
• venetoclax (used to treat cancer)
• cyclosporine (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 antagonists" (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 conditions listed above (or if you are unsure), consult your doctor or
pharmacist before taking Posaconazole HCl.
Posaconazole HCl with food and drink
To increase the absorption of posaconazole, it should be taken during or immediately after a meal or nutritional supplement whenever possible (see section 3 “How to take Posaconazole HCl”). There is no information on the effect of alcohol on posaconazole.
Pregnancy and breastfeeding
Inform your doctor before taking Posaconazole HCl if you are pregnant or suspect you may be pregnant.
Do not take Posaconazole HCl during pregnancy unless specifically instructed by your doctor.
If you are a woman of childbearing age, 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 HCl.
Do not breastfeed while being treated with Posaconazole HCl. This is because small amounts may pass into breast milk.
Driving and using machines
During treatment with Posaconazole HCl, you may experience dizziness, drowsiness, or blurred vision, which may affect your ability to drive or operate tools or machinery. If this occurs, do not drive or use tools or machinery and contact your doctor.
Posaconazole HCl contains glucose
Posaconazole HCl contains approximately 1.75 g of glucose in every 5 mL of suspension. If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.
Posaconazole HCl contains sodium
This medicine contains less than 1 mmol (23 mg) per 5 mL of suspension, i.e., essentially 'sodium-free'.
Posaconazole HCl contains propylene glycol
This medicine contains up to 5.2 mg of propylene glycol (E1520) per 5 mL of suspension.
Posaconazole HCl contains sodium benzoate
This medicine contains 11.4 mg of sodium benzoate (E211) in every 5 mL of suspension.
Posaconazole HCl contains benzoic acid
This medicine contains up to 0.114 mg of benzoic acid (E210) in every 5 mL of suspension.

3. How to take Posaconazole AHCL

Do not switch from taking posaconazole oral suspension to posaconazole tablets or posaconazole gastro-resistant oral suspension without consulting your doctor or pharmacist, as this may result in reduced effectiveness or an increased risk of adverse reactions.
Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. Your doctor will monitor your response and condition to determine how long you should continue taking Posaconazole AHCL and whether any adjustment of the daily dose is needed.
The following table shows the recommended dose and duration of treatment, which depend on the type of infection you have. These may be adjusted by your doctor according to your individual needs. Do not change the dose or treatment regimen on your own without consulting your doctor.
Whenever possible, you should take posaconazole during or immediately after a meal or a nutritional supplement.

If you take more Posaconazole AHCL than you should
If you think you have taken too much, contact your doctor or healthcare provider immediately.

If you forget to take Posaconazole AHCL
If you forget to take a dose, take it as soon as you remember and then continue as before. However, if it is almost time for your next dose, take it at the scheduled time. Do not take a double dose to make up for the missed dose.

If you have any 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 everyone 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-coloured 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: may affect up to 1 in 10 people

• changes in blood salt levels detected in blood tests – signs include feeling confused or weak
• abnormal skin sensations such as numbness, tingling, itching, goosebumps, pricking or burning
• headache
• low blood potassium levels – detected in blood tests
• low magnesium levels – detected in blood tests
• high blood pressure
• loss of appetite, stomach ache or stomach discomfort, passing wind, dry mouth, taste disturbances
• 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 infections and can be detected in blood tests
• fever
• feeling weak, dizzy, tired or sleepy
• rash
• itching
• constipation
• rectal discomfort

Uncommon: may affect up to 1 in 100 people

• anaemia – signs include headache, feeling tired or dizzy, shortness of breath, 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 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 by 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 oxygen supply to the spleen (splenic infarction) – this may cause severe stomach pain
• severe kidney problems – signs include increased or decreased urine production with unusual colour
• high creatinine levels in the blood – detected in blood tests
• cough, hiccups
• nosebleeds
• severe sharp chest pain during breathing (pleuritic pain)
• swollen lymph glands (lymphadenopathy)
• reduced sensation, especially in 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)
• complete or partial inability to speak
• swelling of the mouth
• abnormal dreams or difficulty sleeping
• problems with coordination or balance
• inflammation of the mucosa
• 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: 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 skin peeling
• mental problems such as hearing voices or seeing things that are not there
• fainting
• problems with 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 blind or dark 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 intestinal contents from passing to 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", low levels 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
• hearing disturbances
• 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 PosaconazoleAHCL.
• 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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Posaconazole HCl

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions.
• If any suspension remains in a bottle that was opened more than 30 days ago, do not use this medicine. Return the bottle containing the remaining solution to the pharmacist.
• 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. Package contents and other information

What Posaconazole AHCL contains

• The active substance is posaconazole. Each millilitre of oral suspension contains 40 milligrams of posaconazole. The excipients of the suspension are macrogol glycerol hydroxystearate, sodium citrate dihydrate, citric acid monohydrate, simethicone emulsion (containing polydimethylsiloxane, polyethylene glycol sorbitan tristearate, methylcellulose, stearated polyethylene glycol silica gel, sorbic acid (E200), benzoic acid (E210) and sulphuric acid (E513)), xanthan gum (E415), sodium benzoate (E211), liquid glucose, glycerol (E422), titanium dioxide (E171), artificial strawberry flavour containing propylene glycol, and purified water.

Description of the appearance of Posaconazole AHCL and contents of the pack
Posaconazole AHCL is a white to off-white fluid suspension, contained in an amber glass bottle.
A dosing spoon is provided with each bottle to measure doses of 2.5 and 5 mL of oral suspension.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona s/n,
Edifici Est, 6a planta, Barcelona,
08039 Barcelona, Spain

Manufacturer
Accord Healthcare Polska Sp. z o.o.
ul. Lutomierska 50
95-200 Pabianice
Poland
Laboratori Fundacio Dau
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona
Spain
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta

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.