Label: information for the user

Noxafil 300 mg concentrate for infusion solution

posaconazol

Read this label carefully before starting tousethis medication, because it contains important information for you.

• Keep this label, as you may need to read 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 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". Noxafil is used to prevent and treat many different types of fungal infections.

Noxafil acts 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 familyAspergillus.

Noxafil can be used in adults and children aged 2 years or older to treat the following types of fungal infections:

• Infections caused by fungi of the familyAspergillusthat have not improved during treatment with antifungal medications amphotericin B or itraconazole or when treatment with these medications has had to be interrupted;
• Infections caused by fungi of the familyFusariumthat have not improved during treatment with amphotericin B or when treatment with amphotericin B has had to be interrupted;
• 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 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 has had to be interrupted.

Noxafilcan also be used to prevent fungal infections in adults and children aged 2 years or older with a 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 use Noxafil

• if you are allergic to posaconazole or any of the other ingredients in this medicine (listed in section6).

• if you are taking: terfenadine, astemizol, 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 use Noxafil if you are in any of the above circumstances. If in doubt, consult your doctor or pharmacist before taking Noxafil.

See the section “Using Noxafil with other medicines” later for information 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 Noxafil.
• you have a heart rhythm alteration (ECG) that shows a problem called QTc prolongation.
• 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, as you may be more sensitive to UV sunlight.

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

Children

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

Using 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)
• astemizol (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 severe 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 severe reduction of 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 Noxafil.

Other medicines

See the list provided earlier with the medicines that you should not use while taking Noxafil. In addition to the medicines mentioned above, there are other medicines that present a risk of heart rhythm problems, which may be greater when taken with posaconazole. 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 Noxafil side effects 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:

• rifabutina and rifampicina (used to treat certain infections). If you are already taking rifabutina, you will need to have blood tests, as well as be aware of some possible side effects of rifabutina.
• phenytoin, carbamazepine, phenobarbital or primidona (used to treat or prevent seizures).
• efavirenz and fosamprenavir, used to treat HIV infection.
• flucloxacillin (an antibiotic used to treat bacterial infections).

Noxafil may increase the risk of side 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, verapamilo, 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)
• acid transretinoico (ATRA), also known as tretinoína (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.

Pregnancy and breastfeeding

Inform your doctor if you are or think you may be pregnant before starting to take Noxafil. Do not use 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 Noxafil. 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 dizziness, drowsiness 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

The maximum daily dose recommended for this medicine contains 924mg of sodium (found in table salt). This is equivalent to 46% of the maximum daily sodium intake recommended for an adult.

Consult your doctor or pharmacist if you need Noxafil 300mg concentrate for solution for infusion or more daily doses for a prolonged period, especially if you have been recommended a low-sodium diet.

Noxafil contains cyclodextrin

This medicine contains 6,680mg of cyclodextrin per vial.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose for adults is 300 mg twice a day on the first day and then 300 mg once a day.

The recommended dose for children from 2 years to less than 18 years is 6 mg/kg up to a maximum of 300 mg twice a day on the first day and, subsequently, 6 mg/kg up to a maximum of 300 mg once a day.

Your pharmacist or nurse will dilute Noxafil Concentrate for Solution for Infusion to the correct concentration.

Only a healthcare professional will prepare and administer Noxafil Concentrate for Solution for Infusion.

Noxafil will be administered to you:

• through a plastic tube placed in your vein (intravenous infusion)
• usually for 90 minutes

The duration of treatment may depend on the type of infection you have or the length of time your immune system is not functioning correctly, and may be adjusted individually for you by your doctor..Do not adjust your dose yourself before consulting your doctor, or change your treatment regimen.

If you forgot a dose of Noxafil

Since this medication is administered under strict medical supervision, it is unlikely that a dose will be missed. However, if you think you may have forgotten to administer a dose, inform your doctor or pharmacist.

When your doctor stops treatment with Noxafil, you should not experience any side effects.

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, which include yellowing of the skin or the white of the eyes, dark or unusual urine, pale stools, 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
• swelling, redness and pain along the vein in which Noxafil was administered
• 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

Rare: 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 have 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 severe stomach pain
• interruption of oxygen supply to the spleen (splenic infarction), which may cause severe stomach pain
• severe kidney problems, whose signs include increased or decreased urination with urine that is a different color from 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, sensitivity to light
• hair loss (alopecia)
• mouth ulcers
• chills, usual 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 unease
• inflammation or pain at the injection site

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 and large spots on the skin (thrombotic thrombocytopenic purpura)
• inflammation of the face or tongue
• depression
• double vision
• 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 causes high blood pressure with low potassium levels (appears in blood tests)

Unknown frequency: cannot be estimated from available data

• some patients have also reported feeling confused after taking Noxafil

• skin redness

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.

Store in refrigerator (between2°Cand8°C).

Once prepared, the medication must be used immediately. If not used immediately, the solution can be stored for up to 24hours between2°Cand8°C (in refrigerator). This medication is for single useand all the solution that has not been used must be discarded.

Medications should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Noxafil

• The active ingredient is posaconazole. Each vial contains 300 mg of posaconazole.
• The other components are: sulfobutyl ether beta-cyclodextrin sodium (SBECD), disodium edetate, hydrochloric acid (concentrated), sodium hydroxide, water for injection.

Appearance of the product and contents of the container

Noxafil concentrated for solution for infusion is a transparent, colorless to yellow liquid. Variations in color that fall within this range do not affect the quality of the medication.

This medication is available in a single-use glass vial closed with a bromobutyl rubber stopper and an aluminum crimp.

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

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

Other sources of information

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

--------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Instructions for the administration of Noxafil concentrated solution for infusion

• Refrigerate the Noxafil vial until it reaches room temperature.
• Transfer 16.7 ml of posaconazole from the refrigerated vial to a bag (or bottle) for intravenous infusion that contains a compatible diluent mixture (see below the list of diluents) using a volume range of 150 ml to 283 ml depending on the final concentration desired (not less than 1 mg/ml and not more than 2 mg/ml).
• Administer through a central venous catheter, which includes a central venous catheter or a peripheral central catheter (PCC), via a slow intravenous infusion over approximately 90 minutes. Noxafil concentrated solution for infusion should not be administered as a bolus.
• If a central venous catheter is not available, a single infusion can be administered through a peripheral venous catheter with the appropriate volume to achieve a dilution of approximately 2 mg/ml. In this case, the infusion should be administered over approximately 30 minutes.

Nota: in clinical studies, multiple peripheral infusions through the same vein resulted in the appearance of reactions at the infusion site (see section4.8).

• Noxafil is for single use only.

The following medications can be infused simultaneously with Noxafil concentrated solution for infusion and through the same intravenous route (or cannula):

Noxafil should not be administered simultaneously with any medication that is not listed in this table through the same intravenous route (or cannula).

Before administration, the infusion solution should be visually inspected for the presence of particles.The solution of Noxafil ranges from colorless to pale yellow. Variations in color that fall within this range do not affect the quality of the medication.

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Noxafil should not be diluted with:

This medication should not be mixed with other medications, except for the ones listed below:

Glucose 5% in water

Sodium chloride 0.9%

Sodium chloride 0.45%

Glucose 5% and sodium chloride 0.45%

Glucose 5% and sodium chloride 0.9%

Glucose 5% and 20 mEq of KCl