Label: Information for the User

Noxafil 40mg/ml Oral Suspension

posaconazol

Read this label carefully before starting to take this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section4.

Noxafil contains a medication called posaconazol, which belongs to a group of medications called "antifungals". It is used to prevent and treat many different types of fungal infections.

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

Noxafil can be used in adults to treat the following types of fungal infections when other antifungal medications have not worked or you have had to stop taking them:

• Infections caused by fungi from the familyAspergillusthat have not improved during treatment with the antifungal medications amphotericin B or itraconazole or when treatment with these medications had to be interrupted;
• Infections caused by fungi from the familyFusariumthat have not improved during treatment with amphotericin B or when treatment with amphotericin B had to be interrupted;
• Infections caused by fungi that cause the diseases known as “chromoblastomycosis” and “mycetoma” that have not improved during treatment with itraconazole or when treatment with itraconazole had to be interrupted;
• Infections caused by a fungus calledCoccidioidesthat have not improved during treatment with one or more medications, amphotericin B, itraconazole, or fluconazole, or when treatment with these medications had to be interrupted;
• Infections in the mouth or throat area (called “aphthae”) caused by fungi calledCandida, that have not been previously treated.

This medication can also be used to prevent fungal infections in adults at high risk of contracting a fungal infection, such as:

• Patients with a weakened immune system as a result of having received chemotherapy for “acute myeloid leukemia” (AML) or “myelodysplastic syndromes” (MDS)
• Patients receiving “high doses of immunosuppressive treatment” after a “hematopoietic stem cell transplant” (HSCT).

Do not take Noxafil

• if you are allergic to posaconazole or any of the other ingredients in this medicine (listed in section6).
• if you are taking: terfenadine, astemizole, cisaprida, pimozida, halofantrina, quinidina, any medicine that contains "ergot alkaloids", such as ergotamine or dihydroergotamine, or a "statin", such as simvastatina, atorvastatina or lovastatina.
• if you have just started taking venetoclax or your dose of venetoclax is being slowly increased for the treatment of chronic lymphocytic leukemia (CLL).

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

See the section “Taking Noxafil with other medicines” later for more information, including that related to 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 diarrhea or vomiting, as these situations may limit the effectiveness of this medicine.
• you have a heart rhythm alteration (ECG) that shows a problem called prolongation of the QTc interval.
• you have heart muscle weakness or heart failure.
• you have a very slow heart rate.
• you have any heart rhythm alteration.
• you have any problem 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 you are being treated. It is important to cover exposed skin areas with protective clothing and use a high-factor sunscreen (SPF) as you may be more sensitive to UV rays from the sun.

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

If you develop severe diarrhea or vomiting (feel unwell) while taking Noxafil, consult your doctor, pharmacist or nurse immediately, as this situation may prevent the medicine from working correctly. For more information, see section4.

Children

Noxafil oral suspension should not be used in children and adolescents (17years of age and younger).

Taking Noxafil with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine.

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

• terfenadine (used to treat allergies)
• astemizole (used to treat allergies)
• cisaprida (used to treat stomach problems)
• pimozida (used to treat symptoms of Tourette's syndrome and mental illnesses)
• halofantrina (used to treat malaria)
• quinidina (used to treat heart rhythm alterations).

Noxafil may increase the amount of these medicines in your blood, which could cause very 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 severe reduction in blood flow to your fingers or toes and damage them.

• a "statin", such as simvastatina, atorvastatina or lovastatina 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 Noxafil if you are in any of the above circumstances. If in doubt, consult your doctor or pharmacist before taking this medicine.

Other medicines

See 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 present a 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 adverse effects of Noxafil by increasing the amount of Noxafil in your blood.

The following medicines may reduce the effectiveness of Noxafil by reducing its levels in your blood:

• rifabutina and rifampicina (used to treat certain infections). If you are already taking rifabutina, you will need to have a blood test, as well as be aware of some possible adverse effects of rifabutina.
• phenytoin, carbamazepine, phenobarbital or primidona (used to treat or prevent seizures).
• efavirenz and fosamprenavir, used to treat HIV infection.
• flucloxacillin (antibiotic used to treat bacterial infections).
• medicines used to reduce stomach acidity such as cimetidine and ranitidine or omeprazole and similar medicines called proton pump inhibitors.

Noxafil may possibly increase the risk of adverse effects of other medicines by increasing the amount of these medicines in your blood. These medicines include:

• vincristine, vinblastine and other “vinca alkaloids” (used to treat cancer)
• venetoclax (used to treat cancer)
• ciclosporina (used during or after transplants)
• tacrolimus and sirolimus (used during or after transplants)
• rifabutina (used to treat certain infections)
• medicines used to treat HIV called protease inhibitors (including lopinavir and atazanavir, which are taken with ritonavir)
• midazolam, triazolam, alprazolam or other “benzodiazepines” (used as sedatives or muscle relaxants)
• diltiazem, verapamil, nifedipino, nisoldipino or other “calcium channel blockers” (used to treat high blood pressure)
• digoxina (used to treat heart failure)
• glipizida or other “sulfonilureas” (used to treat high blood sugar levels)
• all-trans retinoic acid (ATRA), also known as tretinoin (used to treat certain blood cancers).

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

Taking Noxafil with food and drink

To improve the absorption of posaconazole, it is best to take it during or immediately after a meal or a drink (see section 3 “How to take Noxafil”). There is no information on the effect of alcohol on posaconazole.

Pregnancy and breastfeeding

Inform your doctor if you are or think you may be pregnant before starting to take Noxafil.

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

If you are a woman who may become pregnant, you should use effective contraceptive measures while taking this medicine. If you become pregnant while taking Noxafil, contact your doctor immediately.

Do not breastfeed 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 glucose

Noxafil contains approximately 1.75g of glucose per 5ml of suspension. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medicine.

Noxafil contains sodium

This medicine contains less than 1mmol of sodium (23mg) per 5ml of suspension; it is essentially “sodium-free”.

Noxafil contains sodium benzoate

This medicine contains 10mg of sodium benzoate (E‑211) per 5ml of suspension.

Noxafil contains benzyl alcohol

This medicine contains up to 1.25mg of benzyl alcohol per 5ml of suspension. Benzyl alcohol may cause allergic reactions.

Noxafil contains propylene glycol

This medicine contains up to 24.75mg of propylene glycol (E‑1520) per 5ml of suspension.

Do not interchange Noxafil oral suspension and Noxafil tablets or Noxafil gastrorresistant powder and oral suspension without consulting your doctor or pharmacist, as this may lead to a lack of efficacy or increase the risk of adverse reactions.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.Your doctor will monitor your response and condition to determine how long you should take Noxafil and if any changes are needed in your daily dose.

The table below shows the recommended dose and treatment duration, which depend on the type of infection you have and may be adapted individually for you by your doctor. Do not adjust your dose yourself before consulting your doctor, nor change your treatment regimen.

Whenever possible, take posaconazole during or immediately after a meal or food.

If you take more Noxafil than you should

If you are concerned that you may have taken too much, inform your doctor or healthcare professional immediately.

If you forget to take Noxafil

If you have forgotten 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 your dose as scheduled. Do not take a double dose to make up for the missed doses.

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

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

Severe side effects

Inform your doctor, pharmacist or nurse immediately if you notice any of the following severe side 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 white of the eyes, dark or pale urine, feeling sick without apparent reason, stomach problems, loss of appetite or unusual weakness or fatigue, an increase in liver enzymes detected in blood tests
• allergic reaction

Other side effects

Inform 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

• an abnormal change in blood salt levels detected in blood tests, whose signs include confusion or weakness
• abnormal sensations in the skin, such as numbness, tingling, itching, crawling, pinching or burning
• headache
• low levels of potassium detected in blood tests
• low levels of magnesium detected in blood tests
• high blood pressure
• loss of appetite, stomach pain or discomfort, flatulence, dry mouth, changes in taste
• heartburn (sensation of burning in the chest that rises to the throat)

• low levels of "neutrophils", a type of white blood cell (neutropenia), which may make you more prone to infections and detected in blood tests

• fever
• sensation of weakness, dizziness, fatigue or drowsiness
• eruption
• itching
• constipation
• rectal discomfort

Uncommon: 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 levels of platelets (thrombocytopenia), detected in blood tests. This may cause bleeding
• low levels of "leukocytes", a type of white blood cell (leucopenia), detected in blood tests. This may make you more susceptible to infections
• high levels of "eosinophils", a type of white blood cell (eosinophilia). This may appear if you present an inflammatory process

• inflammation of blood vessels
• problems with heart rhythm
• seizures (convulsions)
• neurological damage (neuropathy)

• abnormal heart rhythm, detected in an electrocardiogram (ECG), palpitations, slow or fast heart rate, high or low blood pressure
• low blood pressure

• inflammation of the pancreas (pancreatitis). This may cause intense stomach pain
• interruption of oxygen supply to the spleen (splenic infarction), which may cause intense stomach pain
• serious kidney problems, whose signs include increased or decreased urination with urine that presents a different color than usual

• high levels of creatinine in the blood detected in blood tests
• cough, hiccups
• nasal bleeding
• sharp and intense chest pain when breathing (pleuritic pain)
• inflammation of lymph nodes (lymphadenopathy)
• decreased sensitivity, especially in the skin
• tremors
• high or low blood sugar levels
• blurred vision, light sensitivity
• hair loss (alopecia)
• mouth ulcers
• chills, habitual feeling of discomfort
• back or neck pain, arm or leg pain
• fluid retention (edema)
• menstrual problems (abnormal vaginal bleeding)
• insomnia (difficulty sleeping)

• total 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
• nausea, vomiting, cramps and diarrhea of mild to severe, usually caused by a virus, stomach pain
• belching
• sensation of anxiety

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

• pneumonia, whose signs include feeling short of breath and production of discolored mucus
• high blood pressure in the blood vessels of the lungs (pulmonary hypertension), which may cause severe damage to the lungs and heart
• blood clotting 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
• syncope (fainting)
• problems with thinking or speaking, sudden movements, especially in the hands, that you cannot control
• stroke, whose signs include pain, weakness, numbness or tingling in the extremities
• presence of a blind spot or dark spot in the field of vision
• heart failure or heart attack, which may cause cardiac arrest and death, problems with heart rhythm 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 feeling short of breath or chest pain
• bleeding in the stomach or intestines, whose signs include vomiting blood or blood in the stool
• 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 abdominal cramps
• "uricemic hemolytic syndrome" that appears when there is destruction of red blood cells (hemolysis), which may occur with or without kidney failure
• "pancytopenia", low levels of all blood cells (red, white and platelets), detected in blood tests
• purple spots and large patches on the skin (thrombotic thrombocytopenic purpura)
• inflammation of the face or tongue
• depression
• diplopia (double vision)
• mastalgia (breast pain)
• inadequate functioning of the adrenal glands, which may cause weakness, fatigue, loss of appetite, skin discoloration
• inadequate functioning of the pituitary gland, which may cause low levels of certain hormones in the blood that affect the function of male or female sex organs
• hearing problems
• pseudoaldosteronism, which produceshigh blood pressure with low potassium levels (appears in blood tests)

Frequency not known: cannot be estimated from available data

• some patients have also reported feeling confused after taking Noxafil
• skin flushing

Inform 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 thenational notification system included in theAppendix V.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 use this medication after the expiration date that appears on the labelafter CAD. The expiration date is the last day of the month indicated.

Do not freeze.

If there is any suspension left in the bottle after more than four weeks of its first opening, do not use this medication. Return the bottle with the remaining suspension to your pharmacist.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Noxafil

• The active ingredient of Noxafil is posaconazole. Each milliliter of oral suspension contains 40 milligrams of posaconazole.
• The other components of the suspension are polysorbate 80, simethicone, sodium benzoate (E-211), sodium citrate dihydrate, citric acid monohydrate, glycerol, xanthan gum, liquid glucose, titanium dioxide (E-171), artificial cherry flavor that contains benzyl alcohol and propylene glycol (E-1520) and purified water.

Appearance of the product and contents of the container

Noxafil is 105 ml of white oral suspension, with a cherry flavor, packaged in amber glass bottles. Each bottle is provided with a measuring spoon for measuring doses of 2.5 and 5 ml of the oral suspension.

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

Last review date of this leaflet:<{MM/AAAA}><{mes AAAA}>.

Other sources of information

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