NOXAFIL 100 mg GASTRO-RESISTANT TABLETS

Introduction

Package Leaflet: Information for the User

Noxafil 100mg 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 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 get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Noxafil is and what it is used for

Noxafil 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.

Noxafil can be used in adults to treat fungal infections caused by fungi of the Aspergillusfamily.

Noxafil can be used in adults and children aged 2 years and older 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 aged 2 years and older 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 leukaemia" (AML) or "myelodysplastic syndromes" (MDS)
• patients who are receiving "high-dose immunosuppressive treatment" after a "haematopoietic stem cell transplant" (HSCT).

2. What you need to know before you take Noxafil

Do not take Noxafil

• if you are allergic to posaconazole or any of the other ingredients of this medicine (listed in section 6).
• if 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.
• if you have just started taking venetoclax or your dose of venetoclax is being slowly increased for the treatment of chronic lymphocytic leukaemia (CLL).

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

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Noxafil 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 to have blood tests while taking this medicine.
• you develop severe diarrhoea or vomiting, as these conditions can limit the effectiveness of this medicine.
• you have a heart rhythm problem (ECG) that shows a problem called QTc interval prolongation.
• you have weakness of the heart muscle or heart failure.
• you have a very slow heart rate.
• you have any heart rhythm problems.
• you have any problems with the amounts of potassium, magnesium, or calcium in your blood.
• you are taking vincristine, vinblastine, and other "vinca alkaloids" (medicines used to treat cancer).
• you are taking venetoclax (a medicine used to treat cancer).

You should avoid exposure to the sun while taking this treatment. It is important to cover exposed skin areas with protective clothing and use a sunscreen with a high sun protection factor (SPF), as you may be more sensitive to the UV rays of the sun.

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

If you develop severe diarrhoea or vomiting (feel sick) while taking Noxafil, consult your doctor, pharmacist, or nurse immediately, as this condition can prevent the medicine from working properly. For more information, see section 4.

Children

Noxafil should not be given to children under 2 years of age.

Taking Noxafil with other medicines

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

Do not take Noxafil 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).

Noxafil 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. Noxafil 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 leukaemia (CLL).

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

Other medicines

Consult the list provided earlier with the medicines that you should not use while taking Noxafil. 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 Noxafil. 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 Noxafil by increasing the amount of Noxafil in your blood.

The following medicines may decrease the effectiveness of Noxafil 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.
• flucloxacillin (an antibiotic used against bacterial infections).

Noxafil 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)
• ciclosporin (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 "sulphonylureas" (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 Noxafil.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant or think you might be pregnant before you start taking Noxafil.

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

If you are a woman who can become pregnant, you must use effective contraception while taking this medicine. If you become pregnant while taking Noxafil, contact your doctor immediately.

Do not breast-feed while taking Noxafil, as small amounts may pass into breast milk.

Driving and using machines

You may feel dizzy, sleepy, or have blurred vision while taking Noxafil, 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.

Noxafil contains sodium

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

3. How to take Noxafil

Do not switch between Noxafil tablets and Noxafil 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 in doubt, consult your doctor or pharmacist again.

How much to take

The recommended 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 length 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 schedule.

How to take this medicine

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

If you take more Noxafil than you should

If you think you may have taken too much Noxafil, inform your doctor immediately or go to the hospital immediately.

If you forget to take Noxafil

• If you have missed 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 schedule.
• Do not take a double dose to make up for missed doses.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe Adverse Effects

Inform your doctor, pharmacist, or nurse immediately if you notice any of the following severe adverse effects; you may need urgent medical treatment:

• nausea or vomiting (feeling or being sick), diarrhea
• signs of liver problems, including 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 fatigue or weakness, an increase in liver enzymes detected in blood tests
• allergic reaction

Other Adverse Effects

Inform your doctor, pharmacist, or nurse if you notice any of the following adverse 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, fatigue, or drowsiness
• rash
• itching
• constipation
• rectal discomfort

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

• anemia, whose signs include headaches, feeling of fatigue or dizziness, 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
• disruption 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)

• complete or partial inability to speak
• swelling of the mouth

• abnormal dreams or sleep problems

• coordination or balance problems
• mucosal 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 severe 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 feeling bloated, vomiting, severe constipation, loss of appetite, and cramps
• "hemolytic uremic syndrome" that occurs 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, fatigue, 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 Noxafil
• redness of the skin

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

Reporting Adverse Effects

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

5. Storage of Noxafil

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 pack after EXP. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Noxafil Composition

• The active ingredient of Noxafil is posaconazole. Each tablet contains 100 mg of posaconazole.
• The other ingredients are acetate succinate hypromellose, microcrystalline cellulose, hydroxypropylcellulose (E-463), dental type silica, sodium croscarmellose, magnesium stearate, polyvinyl alcohol, macrogol 3350, titanium dioxide (E-171), talc, yellow iron oxide (E-172).

Product Appearance and Package Contents

Noxafil gastro-resistant tablets have a yellow coating, are capsule-shaped, and are marked with the digits "100" on one side. They are packaged in blister packs in boxes of 24 (2x12) or 96 (8x12) tablets.

Only some package sizes may be marketed.

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Prospectus:<{MM/AAAA}><{month AAAA}>.

Other Sources of Information

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