Noxafil 40 mg/ml oral suspension

Patient Information Leaflet

Introduction

Patient Information Leaflet

Noxafil 40mg/ml oral suspension

posaconazole

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Noxafil is and what it is used for

Noxafil contains a medicine called posaconazole, which belongs to a group of medicines known as "antifungals". It is used to prevent and treat many different fungal infections.

This medicine works by killing or stopping the growth of certain types of fungi that can cause infections.

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

• 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 has had to be discontinued;
• infections caused by fungi of the Fusarium family that have not improved during treatment with amphotericin B or when treatment with amphotericin B has had to be discontinued;
• infections caused by fungi leading to diseases known as “chromoblastomycosis” and “mycetoma” that have not improved during treatment with itraconazole or when treatment with itraconazole has had to be discontinued;
• infections caused by a fungus called Coccidioides that 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 discontinued;
• infections in the mouth or throat area (called “oral thrush”) caused by fungi called Candida, which have not been previously treated.

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

• patients with a weakened immune system due to receiving chemotherapy for "acute myelogenous leukemia" (AML) or "myelodysplastic syndromes" (MDS);
• patients receiving "high-dose immunosuppressive therapy" following "hematopoietic stem cell transplantation" (HSCT).

2. What you need to know before taking 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 containing "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 venetoclax dose is being gradually increased for the treatment of chronic lymphocytic leukemia (CLL).

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

See the section “Taking Noxafil with other medicines” below for further information, including details on other medicines that may interact with Noxafil.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting Noxafil if:

• you have had an allergic reaction to another antifungal medicine, such as ketoconazole, fluconazole, itraconazole, or voriconazole.
• you have or have previously 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 a heart rhythm disorder (ECG) showing a problem called QTc interval prolongation.
• you have weakened heart muscle or heart failure.
• you have a very slow heartbeat.
• you have any heart rhythm disorder.
• you have any problems with levels of potassium, magnesium, or calcium 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).

You should avoid exposure to sunlight during treatment. It is important to cover exposed skin areas 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.

If any of the above apply to you (or if you are 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 may prevent the medicine from working properly. For more information, see section 4.

Children

Noxafil oral suspension must not be used in children and adolescents (aged 17 years and younger).

Taking Noxafil with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might 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)
• 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 disorders)

Noxafil may increase the amount of these medicines in your blood, which could cause serious changes in your heart rhythm.

• any medicine containing "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 reduction in blood flow to the fingers of the hands or feet and cause damage.

• 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 Noxafil if any of the above apply to you. If in doubt, consult your doctor or pharmacist before taking this medicine.

Other medicines

Please refer to the list above of medicines you must not use while taking Noxafil. In addition to the medicines mentioned above, there are other medicines that carry a risk of heart rhythm problems, which may be increased when taken with Noxafil. Make sure to inform your doctor about all 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 the blood.

The following medicines may reduce the effectiveness of Noxafil by decreasing its blood levels:

• rifabutin and rifampicin (used to treat certain infections). If you are already taking rifabutin, you will need to have blood tests and monitor for possible adverse 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).
• medicines used to reduce stomach acidity such as cimetidine and ranitidine, or omeprazole and similar medicines called proton pump inhibitors.

Noxafil may increase the risk of adverse effects of other medicines by increasing their levels in the blood. These medicines include:

• vincristine, vinblastine, and other "vinca alkaloids" (used to treat cancer)
• venetoclax (used to treat cancer)
• cyclosporine (used during or after organ transplants)
• tacrolimus and sirolimus (used during or after organ 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 "sulfonylureas" (used to treat high blood sugar levels)
• all-trans retinoic acid (ATRA), also called tretinoin (used to treat certain blood cancers).

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

Taking Noxafil with food and drink

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

Pregnancy and breastfeeding

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

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

If you are a woman who could become pregnant, you should use effective contraception 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, drowsy, or experience blurred vision while taking Noxafil, which could affect your ability to drive or use tools or machines. If this occurs, do not drive or operate any tools or machines and contact your doctor.

Noxafil contains glucose

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

Noxafil contains sodium

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

Noxafil contains sodium benzoate

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

Noxafil contains benzyl alcohol

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

Noxafil contains propylene glycol

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

3. How to take Noxafil

Do not interchange Noxafil oral suspension with Noxafil tablets or Noxafil gastro-resistant powder and solvent for oral suspension without consulting your doctor or pharmacist, as this may result in reduced effectiveness or increased risk of adverse reactions.

Follow exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again. Your doctor will monitor your response and condition to determine how long you should take Noxafil and whether any adjustment of your daily dose is needed.

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

Take posaconazole during or immediately after a meal or nutritional drink whenever possible.

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 forget 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 at the scheduled time. Do not take a double dose to make up for forgotten doses.

If you have any further 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 everyone will experience them.

Serious adverse effects

Immediately tell your doctor, pharmacist, or nurse if you notice any of the following serious adverse effects; you may need urgent medical treatment:

• nausea or vomiting (feeling sick or being sick), diarrhoea
• signs of liver problems, including yellowing of the skin or the whites of the eyes, unusually dark urine or pale stools, feeling sick for no apparent reason, stomach problems, loss of appetite, or unusual tiredness or weakness, or increased liver enzymes detected in blood tests
• allergic reaction

Other adverse effects

Tell 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

• changes in blood electrolyte levels detected in blood tests, which may include feeling confused or weak
• abnormal skin sensations such as numbness, tingling, itching, crawling sensations, prickling, 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 discomfort, flatulence, dry mouth, changes in taste sensation
• heartburn (a burning sensation in the chest rising up to the throat)
• low levels of "neutrophils", a type of white blood cell (neutropenia), which may make you more prone to infections and is detected in blood tests
• fever
• feeling weak, dizzy, tired, or drowsy
• rash
• itching
• constipation
• rectal discomfort

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

• anaemia, with signs including headaches, feeling tired or dizzy, shortness of breath, or paleness, and low haemoglobin levels detected in blood tests
• low platelet levels (thrombocytopenia), detected in blood tests. This may cause bleeding
• low levels of "leucocytes", 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 occur if you have an inflammatory condition
• inflammation of blood vessels
• heart rhythm problems
• seizures (fits)
• nerve damage (neuropathy)
• abnormal heart rhythm detected on an 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 to the spleen (splenic infarction), which may cause severe stomach pain
• serious kidney problems, with signs including increased or decreased urination and urine of unusual colour
• high blood creatinine levels, detected in blood tests
• cough, hiccups
• nosebleeds
• sharp, severe chest pain when breathing (pleuritic pain)
• swollen lymph nodes (lymphadenopathy)
• reduced sensation, especially in the skin
• tremors
• high or low blood sugar levels
• blurred vision, sensitivity to light
• hair loss (alopecia)
• mouth ulcers
• chills, general feeling of discomfort
• pain, back or neck pain, pain in arms or legs
• fluid retention (oedema)
• menstrual problems (abnormal vaginal bleeding)
• inability to sleep (insomnia)
• complete or partial inability to speak
• swelling of the mouth
• abnormal dreams or trouble sleeping
• coordination or balance problems
• inflammation of the mucosa
• nasal congestion
• breathing difficulty
• chest discomfort
• feeling bloated
• nausea, vomiting, cramps, and mild to severe diarrhoea, usually caused by a virus, stomach pain
• burping
• feeling restless

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

• pneumonia, with signs including feeling short of breath and producing 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 widespread rash with blisters and skin peeling
• mental problems, such as hearing voices or seeing things that are not there
• fainting
• problems with thinking or speaking, sudden jerky movements, especially in the hands, that you cannot control
• stroke, with signs including 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 may lead to cardiac arrest and death, heart rhythm problems with sudden death
• blood clots in the legs (deep vein thrombosis), with signs including severe pain or swelling of the legs
• blood clots in the lungs (pulmonary embolism), with signs including feeling short of breath or chest pain when breathing
• bleeding in the stomach or intestines, with signs including vomiting blood or blood in stools
• blockage of the intestine (intestinal obstruction), especially of the "ileum". This blockage prevents intestinal contents from passing through the colon, with signs including feeling bloated, vomiting, severe constipation, loss of appetite, and cramping
• "haemolytic uraemic syndrome" which occurs when red blood cells are destroyed (haemolysis), which may occur with or without kidney failure
• "pancytopenia", low levels of all blood cells (red cells, white cells, and platelets), detected in blood tests
• large purple spots on the skin (thrombotic thrombocytopenic purpura)
• swelling of the face or tongue
• depression
• double vision
• breast pain
• inadequate functioning of the adrenal glands, which may cause weakness, tiredness, loss of appetite, skin discolouration
• inadequate functioning of the pituitary gland, which may cause low blood levels of certain hormones affecting male or female sexual organ function
• hearing problems
• pseudoaldosteronism, causing high blood pressure with low potassium levels (detected 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

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide 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 expiry date stated on the label after EXP. The expiry date is the last day of the month indicated.

Do not freeze.

If any suspension remains in the bottle after more than four weeks from first opening, this medicine should not be used. Return the bottle containing the remaining suspension to your pharmacist.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Noxafil

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

Appearance of the product and contents of the container

Noxafil is a white, cherry-flavoured oral suspension, supplied in 105 ml amber glass bottles. Each bottle is provided with a dosing spoon to measure doses of 2.5 ml and 5 ml of the oral suspension.

You can request further information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of the most recent review of this leaflet: <{MM/YYYY}><{month YYYY}>.

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.