Noxafil

Package leaflet: Information for the user

Noxafil 40 mg/mL oral suspension

posaconazole
Please read all of this leaflet carefully before 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 side effect, including those not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4. Contents of this leaflet
  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. 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.
Noxafil may be used in adults to treat the following types of fungal infections when other antifungal medicines have not worked or had to be stopped:

• 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 discontinued;
• 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 discontinued;
• 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 discontinued;
• 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 discontinued;
• infections of the mouth or throat (known as “thrush”) caused by fungi called Candida, which have not been 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 Noxafil

Do not take Noxafil

• if you are allergic to posaconazole or to 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 if the dose of venetoclax is being gradually increased for the treatment of chronic lymphocytic leukemia (CLL). Do not take Noxafil if you have any of the conditions listed above. If you are unsure, consult your doctor or pharmacist before taking Noxafil.

See below “Other medicines and Noxafil” for further information, including details on
other medicines that may interact with Noxafil.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking 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 to have blood tests while taking this medicine.
• you develop severe diarrhoea or vomiting, as these conditions may reduce the effectiveness of this medicine.
• you have an abnormal heart rhythm trace (ECG) showing a problem called prolonged QTc interval.
• you have weakened heart muscle 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).
• you are taking venetoclax (a medicine used to treat cancer). During treatment, you must avoid exposure to sunlight. It is important to cover sun-exposed skin areas with protective clothing and to use sunscreen with a high sun protection factor (SPF), as increased sensitivity of the skin to UV rays from sunlight may occur.

If you have any of the conditions listed above (or if you are unsure), consult your doctor,
pharmacist, or nurse before taking Noxafil.
If you develop severe diarrhoea or vomiting (feeling unwell) while taking Noxafil, contact your
doctor, pharmacist, or nurse immediately, as this may prevent the medicine from working
properly. See section 4 for more information.
Children
Noxafil oral suspension must not be used in children and adolescents (aged 17 years or younger).
Other medicines and Noxafil
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:

• 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). Noxafil may increase the levels of these medicines in the blood, which could lead to very serious changes in heart rhythm.
• any medicine containing “ergot alkaloids” such as ergotamine or dihydroergotamine, used to treat migraine. Noxafil may increase the levels of these medicines in the blood, which could lead to a severe reduction in blood flow to the fingers or toes and may damage them.
• 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 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 you are taking
Noxafil. 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 Noxafil. Make sure you
inform your doctor about all medicines you are taking (with or without a prescription).
Some medicines may increase the risk of side effects from Noxafil by increasing the amount of Noxafil in the blood.
The following medicines may reduce the effectiveness of Noxafil by decreasing the amount of Noxafil 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 be cautious about 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).
• medicines used to reduce stomach acid such as cimetidine and ranitidine, or omeprazole and similar medicines called proton pump inhibitors.

Noxafil may likely increase the risk of side effects from certain other medicines by increasing their levels in the blood. These medicines include:

• vincristine, vinblastine, and other “vinca alkaloids” (used to treat tumours)
• venetoclax (used to treat cancer)
• ciclosporin (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 administered 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 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 Noxafil.
Noxafil with food and drinks
To increase the absorption of posaconazole, it should be taken with food or a nutritional supplement whenever possible, either during or immediately after a meal (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 before taking Noxafil if you are pregnant or suspect you may be pregnant.
Do not take Noxafil 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 Noxafil.
Do not breastfeed while being treated with Noxafil. This is because small amounts may pass into breast milk.
Driving and using machines
While being treated with Noxafil, you may experience dizziness, drowsiness, or blurred vision, which could affect your ability to drive or operate tools or machinery. If this occurs, do not drive or operate tools or machinery, and contact your doctor.
Noxafil contains glucose
Noxafil contains approximately 1.75 g of glucose per 5 mL of suspension. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine. It may be harmful to teeth.
Noxafil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 5 mL of suspension, i.e. essentially “sodium-free”.
Noxafil contains sodium benzoate
This medicine contains 10 mg of sodium benzoate (E211) 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. Ask your doctor or pharmacist for advice if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause side effects (such as metabolic acidosis).
Noxafil contains propylene glycol
This medicine contains up to 24.75 mg of propylene glycol (E1520) per 5 mL of suspension.

3. How to take Noxafil

Do not switch from Noxafil oral suspension to Noxafil tablets or Noxafil gastro-resistant powder and
solvent for oral suspension without consulting your doctor or pharmacist, as this may result in
lack of effectiveness or an increased risk of adverse reactions.
Take this medicine exactly as directed 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 take Noxafil and whether any adjustment of the daily dose is necessary.
The following table shows the recommended dose and duration of treatment, which depend on the type of
infection you have, and 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 with food or immediately after a meal or nutritional supplement.

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

If you forget to take Noxafil
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 the next dose, take it at the scheduled time. Do not take a double
dose to make up for a forgotten dose.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody 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 (feeling or being unwell), diarrhoea
• signs of liver problems, including yellowing of the skin or the white part of the eyes, unusually dark urine or pale stools, unexplained feeling of malaise, 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: these may affect up to 1 in 10 people

• changes in blood salt levels detected in blood tests – signs include feeling confused or weak
• abnormal sensations of the skin, such as numbness, tingling, itching, goosebumps, 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 ache or stomach discomfort, passing wind, dry mouth, taste changes
• 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 getting infections and can be detected in blood tests
• fever
• feeling weak, dizzy, tired or sleepy
• rash
• itching
• constipation
• rectal discomfort

Uncommon: these may affect up to 1 in 100 people

• anaemia – signs include headache, feeling tired or dizzy, shortness of breath or pale appearance, and low haemoglobin levels detected in blood tests
• low platelet count (thrombocytopenia) detected in blood tests – this may lead to bleeding
• low level of "leucocytes", a type of white blood cell (leucopenia) detected in blood tests – this may increase the risk of getting infections
• high level 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 on 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 and oxygen to the spleen (splenic infarction) – this may cause severe stomach pain
• severe kidney problems – signs include increased or decreased urine production with urine of unusual colour
• high creatinine levels – detected in blood tests
• cough, hiccups
• nosebleed
• severe sharp chest pain during breathing (pleuritic pain)
• swollen lymph nodes (lymphadenopathy)
• reduced sensation, especially of 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)
• being completely or partially unable 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: these may affect up to 1 in 1,000 people

• pneumonia – signs include feeling short of breath and coughing up discoloured sputum
• high blood pressure in the blood vessels of the lungs (pulmonary hypertension), which can cause severe damage to the lungs and heart
• blood problems such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including widespread blistering rash and skin peeling
• mental problems such as hearing voices or seeing things that are not there
• fainting
• problems 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 dark or blind spot in your field of vision
• heart failure or heart attack, which may 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 feeling short 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", a low level of all blood cells (red and white blood cells and platelets) detected in blood tests
• extensive 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 changes
• 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 Noxafil
• redness of the skin

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 detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 refers to the
last day of that month.
Do not freeze.
If any suspension remains in a bottle opened for the first time for more than four weeks, do not use this
medicine. Return the bottle containing the remaining suspension to the pharmacist.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose
of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Noxafil contains

• The active substance in Noxafil is posaconazole. Each millilitre of oral suspension contains 40 milligrams of posaconazole.
• The excipients in the oral suspension are polysorbate 80, simethicone, sodium benzoate (E211), dihydrated sodium citrate, monohydrated citric acid, glycerol, xanthan gum, liquid glucose, titanium dioxide (E171), artificial cherry flavour containing benzyl alcohol and propylene glycol (E1520), and purified water.

Description of the appearance of Noxafil and contents of the pack
Noxafil is a white, cherry-flavoured oral suspension, supplied in 105 mL amber glass bottles. Each bottle comes with a dosing spoon to measure doses of 2.5 mL and 5 mL of oral suspension.

Marketing Authorisation Holder
Manufacturer
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands
Organon Heist bv
Industriepark 30
2220 Heist-op-den-Berg
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

Lietuva
UAB Merck Sharp & Dohme
Tel. +370 5 2780 247
[email protected]

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
[email protected]

Luxembourg/Luxemburg
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

Česká republika
Merck Sharp & Dohme s.r.o.
Tel: +420 277 050 000
[email protected]

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
[email protected]

Danmark
MSD Danmark ApS
Tlf.: +45 4482 4000
[email protected]

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
[email protected]

Deutschland
MSD Sharp & Dohme GmbH
Tel.: +49 (0)89 20 300 4500
[email protected]

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
[email protected]

Eesti
Merck Sharp & Dohme OÜ
Tel: +372 614 4200
[email protected]

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
[email protected]

Ελλάδα
MSD Α.Φ.Ε.Ε.
Τηλ: +30 210 98 97 300
[email protected]

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0)1 26 044
[email protected]

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
[email protected]

Polska
MSD Polska Sp. z o.o.
Tel: +48 22 549 51 00
[email protected]

France
MSD France
Tél: +33 (0)1 80 46 40 40
[email protected]

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
[email protected]

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: +385 1 6611 333
[email protected]

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
[email protected]

Ireland
Merck Sharp & Dohme Ireland (Human Health) Limited
Tel: +353 (0)1 2998700
[email protected]

Slovenija
Merck Sharp & Dohme, inovativna zdravila d.o.o.
Tel: +386 1 520 4201
[email protected]

Ísland
Vistor ehf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Merck Sharp & Dohme, s.r.o.
Tel: +421 2 58282010
[email protected]

Italia
MSD Italia S.r.l.
Tel: 800 23 99 89 (+39 06 361911)
[email protected]

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
[email protected]

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673 (+357 22866700)
[email protected]

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
[email protected]

Latvija
SIA Merck Sharp & Dohme Latvija
Tel.: +371 67025300
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu https://www.ema.europa.eu.

Patient Information Leaflet: Information for the User

Noxafil 100 mg gastro-resistant tablets

posaconazole
Please read this entire leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. 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. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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. It belongs to a group of medicines known as "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.
Noxafil can be used in adults and children aged 2 years and older with a body weight above 40 kg to treat the following types of fungal infections:

• infections caused by fungi of the Aspergillus family;
• 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 discontinued;
• 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 discontinued;
• 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 discontinued.

This medicine can also be used to prevent fungal infections in adults and children aged 2 years and older with a body weight above 40 kg 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 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 if the dose of venetoclax is being gradually increased for the treatment of chronic lymphocytic leukemia (CLL).

Do not take Noxafil if you have any of the above conditions. If you are unsure, consult your doctor or pharmacist before taking Noxafil.
See below "Other medicines and Noxafil" for further information, including details on other medicines that may interact with Noxafil.

Warnings and precautions

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

• you have had an allergic reaction to another antifungal medicine such as ketoconazole, fluconazole, itraconazole, or voriconazole.
• you have or have ever 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 heart rhythm trace (ECG) showing a problem called prolonged QTc interval.
• you have weakened heart muscle 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).
• you are taking venetoclax (a medicine used to treat cancer). During treatment, you must avoid exposure to sunlight. 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 you have any of the above conditions (or if you are unsure), consult your doctor, pharmacist, or nurse before taking Noxafil.
If you develop severe diarrhea or vomiting (feeling unwell) while taking Noxafil, contact your doctor, pharmacist, or nurse immediately, as this may prevent the medicine from working properly. See section 4 for more information.

Children

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

Other medicines and Noxafil

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:

• 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). Noxafil can increase the levels of these medicines in the 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. Noxafil can increase the levels of these medicines in the blood, which may lead to a severe reduction in blood flow to the fingers of the hands or feet and may damage them.
• a "statin" such as simvastatin, atorvastatin, or lovastatin, used to treat high cholesterol levels.
• venetoclax if used at the beginning of treatment for a type of cancer, chronic lymphocytic leukemia (CLL).

Do not take Noxafil if you have any of the above conditions. 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 you are taking Noxafil. In addition to the medicines listed above, there are other medicines that carry a risk of rhythm disturbances, which may be greater when taken with Noxafil. Make sure you inform your doctor about all medicines you are taking (with or without prescription).
Some medicines may increase the risk of side effects of Noxafil by increasing the amount of Noxafil in the blood.
The following medicines may reduce the effectiveness of Noxafil by decreasing the amount of Noxafil 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 be cautious about 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 likely increase the risk of side effects of some other medicines by increasing their levels in the blood. These medicines include:

• vincristine, vinblastine, and other "vinca alkaloids" (used to treat tumors)
• venetoclax (used to treat cancer)
• ciclosporin (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, 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 above conditions (or if you are unsure), consult your doctor or pharmacist before taking Noxafil.

Pregnancy and breastfeeding

Inform your doctor before taking Noxafil if you are pregnant or suspect you may be pregnant.
Do not take Noxafil during pregnancy unless specifically instructed by your doctor.
If you are a woman of childbearing potential, you must use an effective method of contraception while taking this medicine. Contact your doctor immediately if you become pregnant while being treated with Noxafil.
Do not breastfeed while being treated with Noxafil. This is because small amounts may pass into breast milk.

Driving and using machines

While being treated with Noxafil, you may experience dizziness, drowsiness, or blurred vision, which could 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.

Noxafil contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take Noxafil

Do not switch from Noxafil tablets to Noxafil 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 your doctor or pharmacist has told you. If
you have any doubts, consult your doctor or pharmacist.
How much to take
The usual dose is 300 mg (three 100 mg tablets) twice on the first day, followed by
300 mg (three 100 mg tablets) once daily thereafter.
The duration of treatment may depend on the type of infection you have and may be individually adjusted for you by your doctor. Do not adjust the dose on your own or change the treatment regimen without first consulting your doctor.
How to take this medicine

• Swallow the tablet whole with water.
• Do not crush, chew, break, or dissolve the tablet.
• Tablets may be taken with or without food.

If you take more Noxafil than you should
If you think you may have taken more Noxafil than you should, inform a doctor or go
immediately to hospital.
If you forget to take Noxafil

• If you forget to take a dose, take it as soon as you remember.
• However, if it is almost time for your next dose, skip the missed dose and return to your regular dosing schedule.
• Do not take a double dose to make up for a forgotten dose.

If you have any doubts about how to use this medicine, consult 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
Immediately inform your doctor, pharmacist, or nurse if you notice any of the following serious side effects – you may need urgent medical treatment:

• nausea or vomiting (feeling unwell), diarrhoea
• signs of liver problems, including yellowing of the skin or the white part of the eyes, unusually dark-coloured urine or pale stools, unexplained feeling of malaise, 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, 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 ache or stomach discomfort, intestinal gas, 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 cells (neutropenia) – this may increase the risk of infections and can be detected in blood tests
• fever
• feeling weak, dizzy, tired, or sleepy
• skin 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 cells (leucopenia) detected in blood tests – this may increase the risk of infections
• high levels of "eosinophils", a type of white blood cells (eosinophilia) – this may occur if you have inflammation
• inflammation of blood vessels
• changes in heart rhythm
• seizures
• nerve damage (neuropathy)
• abnormal heart rhythm – detected on 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) – this may cause severe stomach pain
• severe kidney problems – signs include increased or decreased urine production with urine of unusual colour
• high creatinine levels – detected in blood tests
• cough, hiccups
• nosebleeds
• severe sharp chest pain during breathing (pleuritic pain)
• swelling of 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 malaise
• pain, back pain or neck pain, pain in arms or legs
• fluid retention (oedema)
• menstrual disorders (abnormal vaginal bleeding)
• inability to sleep (insomnia)
• being completely or partially unable 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 severe damage to the lungs and heart
• blood problems such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including widespread blistering skin rash 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 dark or blind spot in your field of vision
• heart failure or heart attack, which may 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 during 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 into 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", a low level of all blood cells (red and white blood cells and platelets) detected in blood tests
• extensive 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 male or female sexual organ function
• 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 Noxafil
• 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 those 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 Noxafil

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Do not dispose of medicines 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 Noxafil contains

• The active substance in Noxafil is posaconazole. Each tablet contains 100 mg of posaconazole.
• The other components are: hypromellose acetate succinate; microcrystalline cellulose; hydroxypropylcellulose (E463); colloidal anhydrous silica; sodium croscarmellose; magnesium stearate; polyvinyl alcohol; macrogol 3350; titanium dioxide (E171); talc; yellow iron oxide (E172).

Description of the appearance of Noxafil and contents of the pack
Noxafil gastro-resistant tablets are yellow, capsule-shaped tablets, marked with "100" on one side, packaged in blisters in packs of 24 (2x12) or 96 (8x12) tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Manufacturer
Marketing Authorisation Holder Organon Heist bv
Merck Sharp & Dohme B.V. Industriepark 30
Waarderweg 39 2220 Heist-op-den-Berg
2031 BN Haarlem Belgium
The Netherlands
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

Lietuva
UAB Merck Sharp & Dohme
Tel. +370 5 2780 247
[email protected]

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
[email protected]

Luxembourg/Luxemburg
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

Česká republika
Merck Sharp & Dohme s.r.o.
Tel: +420 277 050 000
[email protected]

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
[email protected]

Danmark
MSD Danmark ApS
Tlf.: +45 4482 4000
[email protected]

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
[email protected]

Deutschland
MSD Sharp & Dohme GmbH
Tel.: +49 (0) 89 20 300 4500
[email protected]

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
[email protected]

Eesti
Merck Sharp & Dohme OÜ
Tel: +372 614 4200
[email protected]

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
[email protected]

Ελλάδα
MSD Α.Φ.ΕΕ.
Τηλ: +30 210 98 97 300
[email protected]

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
[email protected]

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
[email protected]

Polska
MSD Polska Sp. z o.o.
Tel: +48 22 549 51 00
[email protected]

France
MSD France
Tél: +33 (0)1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
[email protected]

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: +385 1 6611 333
[email protected]

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
[email protected]

Ireland
Merck Sharp & Dohme Ireland (Human Health) Limited
Tel: +353 (0)1 2998700
[email protected]

Slovenija
Merck Sharp & Dohme, inovativna zdravila d.o.o.
Tel: +386 1 520 4201
[email protected]

Ísland
Vistor ehf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Merck Sharp & Dohme, s.r.o.
Tel: +421 2 58282010
[email protected]

Italia
MSD Italia S.r.l.
Tel: 800 23 99 89 (+39 06 361911)
[email protected]

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
[email protected]

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673 (+357 22866700)
[email protected]

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
[email protected]

Latvija
SIA Merck Sharp & Dohme Latvija
Tel.: +371 67025300
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu https://www.ema.europa.eu.

Patient Information Leaflet: Information for the User

Noxafil 300 mg concentrate for solution for infusion

posaconazole
Please read this leaflet carefully before using 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 side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Noxafil is and what it is used for
2. What you need to know before using Noxafil
3. How to use 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. It belongs to a group of medicines known as "antifungals". Noxafil is used to prevent and treat many different types of fungal infections.
Noxafil works by killing or stopping the growth of certain types of fungi that can cause infections.
Noxafil can be used in adults and children aged 2 years and older to treat the following types of fungal infections:

• infections caused by fungi of the Aspergillus family;
• 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 discontinued;
• infections caused by fungi causing conditions known as "chromoblastomycosis" and "mycetoma" that have not improved during treatment with itraconazole or when treatment with itraconazole had to be discontinued;
• infections caused by a fungus called Coccidioides that have not improved during treatment with one or more of the medicines amphotericin B, itraconazole or fluconazole, or when treatment with these medicines had to be discontinued.

Noxafil can also be used to prevent fungal infections in adults and children aged 2 years and older 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 should know before using Noxafil

Do not use Noxafil

• if you are allergic to posaconazole or to 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 if your venetoclax dose is being gradually increased for the treatment of chronic lymphocytic leukemia (CLL).

Do not use Noxafil if you have any of the above conditions. If you are unsure, consult your doctor or pharmacist before taking Noxafil.
See below under “Other medicines and Noxafil” for information about other medicines that may interact with Noxafil.

Warnings and precautions

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

• you have had an allergic reaction to another antifungal medicine such as ketoconazole, fluconazole, itraconazole, or voriconazole.
• you have or have ever had liver problems. You may need blood tests while taking Noxafil.
• you have an abnormal heart rhythm trace (ECG) showing a condition called prolonged QTc interval.
• you have weakened heart muscle 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).
• you are taking venetoclax (a medicine used to treat cancer). During treatment, avoid exposure to sunlight. It is important to cover exposed skin areas with protective clothing and to use sunscreen with a high sun protection factor (SPF), as your skin may become more sensitive to UV rays from sunlight.

If you have any of the above conditions (or if you are unsure), consult your doctor, pharmacist, or nurse before using Noxafil.

Children

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

Other medicines and Noxafil

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

Do not take Noxafil 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)

Noxafil can increase the amount of these medicines in your blood, which may lead to serious changes in heart rhythm.

• any medicine containing “ergot alkaloids” such as ergotamine or dihydroergotamine (used to treat migraine). Noxafil 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 may 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 you have any of the above conditions. If you are unsure, consult your doctor or pharmacist before taking Noxafil.

Other medicines

Check the list of medicines above that must not be taken while you are taking Noxafil. In addition to the medicines listed above, there are other medicines that may increase the risk of heart rhythm disturbances when taken with posaconazole. Make sure you inform your doctor about all medicines you are taking (with or without 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 reduce the effectiveness of Noxafil by decreasing the amount of Noxafil in your 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 be cautious about 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 likely increase the risk of side effects of certain other medicines by increasing their levels in the blood. These medicines include:

• vincristine, vinblastine, and other “vinca alkaloids” (used to treat tumours)
• venetoclax (used to treat cancer)
• ciclosporin (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 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 known as tretinoin (used to treat certain blood cancers)

If you have any of the above conditions (or if you are unsure), consult your doctor or pharmacist before taking Noxafil.

Pregnancy and breastfeeding

Inform your doctor before taking Noxafil if you are pregnant or suspect you may be pregnant.
Do not use Noxafil 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 Noxafil.
Contact your doctor immediately if you become pregnant while using Noxafil.
Do not breastfeed while using Noxafil. This is because small amounts of the medicine may pass into breast milk.

Driving and using machines

While being treated with Noxafil, you may experience dizziness, drowsiness, or blurred vision, which could 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.

Noxafil contains sodium

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

Talk to your doctor or pharmacist if you need Noxafil 300 mg concentrate for infusion solution or more per day for a prolonged period, especially if you have been advised to follow a low-salt (low-sodium) diet.

Noxafil contains cyclodextrin

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

3. How to use Noxafil

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended dose in adults is 300 mg twice daily on the first day, followed by 300 mg
once daily thereafter.
The recommended dose in children aged 2 years to less than 18 years is 6 mg/kg up to a
maximum of 300 mg twice daily on the first day, followed by 6 mg/kg up to a maximum of
300 mg once daily thereafter.
Noxafil concentrate for solution for infusion will be diluted to the correct concentration by a pharmacist
or nurse.
Noxafil concentrate for solution for infusion must always be prepared and administered by a
healthcare professional.
Noxafil will be given to you:

• via a plastic tube inserted into a vein (intravenous infusion)
• usually over a period of 90 minutes

The duration of treatment may depend on the type of infection you have or the time since your
immune system began to function improperly, and may be individually adjusted for you by your doctor. Do not adjust the dose yourself without first consulting your doctor, or change your treatment regimen.
If you forget to take a dose of Noxafil
Since this medicine will be administered under strict medical supervision, it is unlikely that
you could forget a dose. However, if you think a dose has been missed, consult your doctor or pharmacist.
When treatment with Noxafil is stopped as directed by your doctor, no withdrawal effects should occur.
If you have any questions about using this medicine, consult your doctor, pharmacist, or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody 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 (feeling or state of sickness), diarrhoea
• signs of liver problems – these include yellowing of the skin or the white part of the eyes, unusually dark-coloured urine or pale stools, unexplained feeling of sickness, 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: these may affect up to 1 in 10 people

• a change in salt levels in the blood detected in blood tests – signs include feeling confused or weak
• abnormal skin sensations such as numbness, tingling, itching, goosebumps, prickling or burning
• swelling, redness and tenderness at the vein used to administer Noxafil
• headache
• low 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 alterations
• 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 getting infections and can be detected in blood tests
• fever
• feeling weak, dizzy, tired or sleepy
• skin rash
• itching
• constipation
• rectal discomfort

Uncommon: these may affect up to 1 in 100 people

• anaemia – signs include headache, feeling tired or dizzy, shortness of breath or 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 getting 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 on 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) – this may cause severe stomach pain
• severe kidney problems – signs include increased or decreased production of urine that is different in colour than usual
• high levels of creatinine – detected in blood tests
• cough, hiccups
• nosebleed
• severe sharp chest pain during breathing (pleuritic pain)
• enlarged lymph nodes (lymphadenopathy)
• reduced sensation, especially of the skin
• tremor
• high or low blood sugar levels
• blurred vision, light sensitivity
• hair loss (alopecia)
• mouth ulcers
• chills, general feeling of illness
• pain, back pain or neck pain, pain in arms or legs
• fluid retention (oedema)
• menstrual disorders (abnormal vaginal bleeding)
• inability to sleep (insomnia)
• being completely or partially unable to speak
• swelling of the mouth
• abnormal dreams or difficulty sleeping
• problems with coordination or balance
• inflammation of mucous membranes
• 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
• inflammation or pain at the injection site

Rare: these 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 can cause severe damage to the lungs and heart
• blood problems such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including widespread 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 dark or blind spot in your field of vision
• heart failure or heart attack which may 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 stools
• blockage in the intestine (intestinal obstruction), especially in "ileus". 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", a low level of all blood cells (red and white blood cells and platelets) detected in blood tests
• extensive 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 changes
• 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 Noxafil
• 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 detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 refers to the last day of that month.
Store in the refrigerator (2°C – 8°C).
Once prepared, the medicine should be used immediately. If not used immediately, the solution can be stored for up to 24 hours at a temperature of 2°C – 8°C (in the refrigerator). This medicine is for single use only, and any unused solution must be discarded.
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 Noxafil contains

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

Description of the appearance of Noxafil and contents of the pack
Noxafil concentrate for solution for infusion is a clear, colourless to yellow liquid. Colour variations within this range do not affect the quality of the medicinal product.
This medicine is supplied in a single-use glass vial closed with a bromobutyl rubber stopper and an aluminium seal.

Marketing Authorisation Holder
Manufacturer
Organon Heist bv
Merck Sharp & Dohme B.V.
Industriepark 30
Waarderweg 39
2220 Heist-op-den-Berg
Belgium
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
[email protected]

Česká republika
Merck Sharp & Dohme s.r.o.
Tel: +420 277 050 000
[email protected]

Danmark
MSD Danmark ApS
Tlf.: +45 4482 4000
[email protected]

Deutschland
MSD Sharp & Dohme GmbH
Tel.: +49 (0)89 20 300 4500
[email protected]

Eesti
Merck Sharp & Dohme OÜ
Tel: +372 614 4200
[email protected]

Ελλάδα
MSD Α.Φ.Ε.Ε.
Τηλ: +30 210 98 97 300
[email protected]

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
[email protected]

France
MSD France
Tél: +33 (0)1 80 46 40 40

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: +385 1 6611 333
[email protected]

Ísland
Vistor ehf.
Sími: +354 535 7000
[email protected]

Ireland
Merck Sharp & Dohme Ireland (Human Health) Limited
Tel: +353 (0)1 2998700
[email protected]

Italia
MSD Italia S.r.l.
Tel: 800 23 99 89 (+39 06 361911)
[email protected]

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673 (+357 22866700)
[email protected]

Latvija
SIA Merck Sharp & Dohme Latvija
Tel.: +371 67025300
[email protected]

Lietuva
UAB Merck Sharp & Dohme
Tel. +370 5 2780 247
[email protected]

Luxembourg/Luxemburg
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
[email protected]

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
[email protected]

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
[email protected]

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
[email protected]

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0)1 26 044
[email protected]

Polska
MSD Polska Sp. z o.o.
Tel: +48 22 549 51 00
[email protected]

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
[email protected]

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
[email protected]

Slovenija
Merck Sharp & Dohme, inovativna zdravila d.o.o.
Tel: +386 1 520 4201
[email protected]

Slovenská republika
Merck Sharp & Dohme, s.r.o.
Tel: +421 2 58282010
[email protected]

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
[email protected]

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:

Instructions for administration of Noxafil concentrate for solution for infusion

• Allow the refrigerated Noxafil vial to reach room temperature.
• Aseptically transfer 16.7 mL of posaconazole to an intravenous infusion bag (or bottle) containing a compatible diluent (see list of diluents below), using a volume between 150 mL and 283 mL depending on the final concentration required (not less than 1 mg/mL and not more than 2 mg/mL).
• Administer via a central venous line, including a central venous catheter or a peripherally inserted central catheter (PICC), by slow intravenous infusion over approximately 90 minutes. Noxafil concentrate for solution for infusion must not be administered as an intravenous bolus.
• If a central venous catheter is not available, a single infusion may be administered via a peripheral venous catheter using a volume sufficient to achieve a dilution of approximately 2 mg/mL. When administered via a peripheral venous catheter, the infusion should be given over approximately 30 minutes. Note: in clinical studies, repeated peripheral infusions into the same vein have led to the development of infusion site reactions (see section 4.8).
• Noxafil is for single use only.

The following medicinal products may be co-administered simultaneously using the same intravenous line (or cannula) used for the administration of Noxafil concentrate for solution for infusion:
Amikacin sulfate
Caspofungin
Ciprofloxacin
Daptomycin
Dobutamine hydrochloride
Famotidine
Filgrastim
Gentamicin sulfate
Hydrochloride
Levofloxacin
Lorazepam
Meropenem
Micafungin
Morphine sulfate
Norepinephrine bitartrate
Potassium chloride
Vancomycin hydrochloride
Any other medicinal product not listed in the table above must not be administered concomitantly with Noxafil using the same intravenous line (or cannula).
Prior to administration, the infusion solution should be visually inspected for particulate matter. The Noxafil solution ranges from colourless to pale yellow. Colour variations within this range do not affect the quality of the medicinal product.
Unused medicinal product and waste material must be disposed of in accordance with local regulations.
Noxafil must not be diluted with:
Lactated Ringer's USP
5% Dextrose with Lactated Ringer's USP
Sodium bicarbonate 4.2% infusion
This medicinal product must not be mixed with other medicinal products except those listed below:
5% Dextrose in water
0.9% Sodium chloride
0.45% Sodium chloride
5% Dextrose and 0.45% Sodium chloride
5% Dextrose and 0.9% Sodium chloride
5% Dextrose and 20 mEq KCl

Package leaflet: Information for the user

Noxafil 300 mg gastro-resistant powder and solvent for oral suspension

posaconazole
Please read this leaflet carefully before taking or administering this medicine to the
child, as 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 only for you or the child. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

1. What Noxafil is and what it is used for
2. What you need to know before you or the child take 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. 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.
Noxafil may be used in children aged 2 years and older to treat the following types of fungal infections:

• infections caused by fungi of the Aspergillus family;
• 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 discontinued;
• 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 discontinued;
• 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 discontinued.

This medicine may also be used to prevent fungal infections in children aged 2 years and older who are at high risk of developing a fungal infection, such as:

• patients with 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 should know before you or the child takes Noxafil

Do not take Noxafil

• if you or the child are allergic to posaconazole or to any of the other ingredients of this medicine (listed in section 6).
• if you or the child 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 or the child 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 Noxafil if you or the child have any of the conditions listed above. If you are
unsure, consult your doctor or pharmacist before taking Noxafil.
See below “Other medicines and Noxafil” for further information, including details on other
medicines that may interact with Noxafil.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Noxafil if you or the child:

• have had an allergic reaction to another antifungal medicine such as ketoconazole, fluconazole, itraconazole, or voriconazole.
• have or have ever had liver problems. You may need to have blood tests while taking this medicine.
• develop severe diarrhoea or vomiting, as these conditions may reduce the effectiveness of this medicine.
• have an abnormal heart rhythm trace (ECG) showing a condition called prolonged QTc interval.
• have weakened heart muscle or heart failure.
• have a very slow heart rate.
• have a heart rhythm disorder.
• have any problems with potassium, magnesium, or calcium levels in the blood.
• are taking vincristine, vinblastine, or other “vinca alkaloids” (medicines used to treat cancer).
• are taking venetoclax (a medicine used to treat cancer). During treatment, avoid exposure to sunlight. It is important to cover exposed skin areas with protective clothing and use sunscreen with a high sun protection factor (SPF), as increased skin sensitivity to UV rays may occur.

If you or the child have any of the conditions listed above (or if you are unsure), consult your
doctor, pharmacist, or nurse before taking Noxafil.
If you or the child develop severe diarrhoea or vomiting (feeling unwell) while taking Noxafil, contact
your doctor, pharmacist, or nurse immediately, as this may prevent the medicine from working
properly. See section 4 for more information.
Noxafil gastro-resistant granules and solvent for oral suspension with food and drinks
This medicine can be taken with or without food.
Alcohol may affect the absorption of this medicine.
Children
Noxafil must not be given to children under 2 years of age.
Other medicines and Noxafil
Inform your doctor or pharmacist if you or the child are taking, have recently taken, or
might take any other medicines.
Do not take Noxafil if you or the child 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). Noxafil may increase the levels of these medicines in the blood, which can lead to very serious changes in heart rhythm.
• any medicine containing “ergot alkaloids” such as ergotamine or dihydroergotamine, used to treat migraine. Noxafil may increase the levels of these medicines in the blood, which can lead to a severe reduction in blood flow to the fingers or toes and may 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 you or the child 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 you or the child are taking Noxafil. In addition to the medicines listed above, there are other medicines that may carry an increased risk of heart rhythm disturbances when taken with Noxafil. Make sure to inform your doctor about all medicines you or the child are taking (with or without prescription).
Some medicines may increase the risk of side effects of Noxafil by increasing the amount of Noxafil in the blood.
The following medicines may reduce the effectiveness of Noxafil by decreasing the amount of Noxafil 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 be cautious about 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 likely increase the risk of side effects of certain other medicines by increasing their levels in the blood. These medicines include:

• vincristine, vinblastine, and other “vinca alkaloids” (used to treat tumours)
• venetoclax (used to treat cancer)
• ciclosporin (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, administered 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 known as tretinoin (used to treat certain blood cancers).

If you or the child have any of the conditions listed above (or if you are unsure), consult your
doctor or pharmacist before taking Noxafil.
Pregnancy and breastfeeding
Inform your doctor before taking Noxafil if you are pregnant or suspect you may be pregnant.
Do not take Noxafil during pregnancy unless your doctor specifically instructs you to do so.
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 Noxafil.
Do not breastfeed while being treated with Noxafil. This is because small amounts may pass into breast milk.
Driving and using machines
During treatment with Noxafil, you may experience dizziness, drowsiness, or blurred vision, which
could 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.
Noxafil contains methyl parahydroxybenzoate and propyl parahydroxybenzoate
This medicine contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216). They may cause allergic reactions (including delayed reactions).
Noxafil contains sorbitol
This medicine contains 47 mg of sorbitol (E420) per mL.
Sorbitol is a source of fructose. If your doctor has told you that you (or the child) are intolerant to certain sugars, or if you have been diagnosed with hereditary fructose intolerance, a rare genetic disorder in which patients cannot metabolize fructose, speak with your doctor before you (or the child) take this medicine.
Noxafil contains propylene glycol
This medicine contains 7 mg of propylene glycol (E1520) per mL.
Noxafil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.

3. How to take Noxafil

Do not switch from taking Noxafil gastro-resistant powder and solvent for oral suspension
to taking Noxafil oral suspension.
Administer this medicine to the child exactly as directed by the doctor or
pharmacist. If you have any doubts, consult the paediatrician or pharmacist.

• Refer to the instructions for use in the leaflet on how to prepare and administer a dose of Noxafil. Keep the leaflet and read it each time you prepare the medicine. Bring this leaflet to the child's medical appointments.
• Make sure that the doctor or pharmacist has explained to you how to mix and administer the correct dose to the child.
• Before use, the powder for oral suspension must be mixed with the solvent provided. Administer to the child within 30 minutes after mixing.
• ONLY the solvent provided in the kit must be used for the preparation of Noxafil.
• To ensure accurate dosing, ONLY use the provided screw-cap syringes for preparation and administration.
• Make sure to follow the doctor’s instructions. The doctor will tell you whether and when to stop administering Noxafil to the child. How much to take The recommended dose for children aged between 2 years and less than 18 years, weighing between 10 and 40 kg, is shown in the table below.

On Day 1, the recommended dose is administered twice.
After Day 1, the recommended dose is administered once daily.
For children weighing > 40 kg, Noxafil tablets are recommended if they are able to swallow the tablets whole.
The duration of treatment may depend on the type of infection or the period during which the immune system is not functioning properly, and may be individually adjusted by the physician. Do not adjust the dose or treatment regimen without first consulting the doctor who prescribed the medicine.

If you or the child takes more Noxafil than you should
If you think that you or the child may have taken more Noxafil than you should, contact a doctor or go to the hospital immediately.

If you forget to take Noxafil

• If you miss a dose, take it or give it to the child as soon as you remember.
• However, if it is almost time for the next dose, skip the missed dose and return to your regular dosing schedule.
• Do not take a double dose to make up for a missed dose.

If you have any questions about the use of this medicine, consult 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 or the child may need urgent medical treatment:

• nausea or vomiting (feeling or being unwell), diarrhoea
• signs of liver problems – these include yellowing of the skin or the whites of the eyes, unusually dark 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: these 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, 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 discomfort or stomach problems, passing wind, dry mouth, altered taste
• 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: these 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 on 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 and oxygen to the spleen (splenic infarction) – this may cause severe stomach pain
• severe kidney problems – signs include increased or decreased urine production with urine of unusual colour
• high creatinine levels – detected in blood tests
• cough, hiccups
• nosebleed
• severe sharp chest pain during breathing (pleuritic pain)
• swelling of the 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)
• being completely or partially unable 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 of bloating
• mild to severe nausea, vomiting, cramps, and diarrhoea, usually caused by a virus, stomach pain
• belching
• feeling nervous

Rare: these 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 can cause severe damage to the lungs and heart
• blood problems such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including widespread 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 dark or blind spot in your field of vision
• heart failure or heart attack, which may 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 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
• extensive 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 changes
• 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 Noxafil
• skin redness

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

Reporting of side effects
If you or the child experience any side effects, including those 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 Noxafil

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after "Exp". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine or solvent via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Refer to the package leaflet for instructions on how to properly dispose of any remaining medicine.

6. Package contents and other information

What Noxafil contains
The active substance is posaconazole. Each single-dose sachet of gastro-resistant powder for oral suspension contains a white to yellowish powder with 300 mg of posaconazole.
The other component is: hypromellose acetate succinate.
The solvent contains the following components: purified water, glycerol (E422), methyl para-hydroxybenzoate (E218), propyl para-hydroxybenzoate, sodium dihydrogen phosphate monohydrate, anhydrous citric acid (E330), xanthan gum (E415), sodium citrate (E331), sodium saccharin (E954), microcrystalline cellulose and sodium carboxymethylcellulose, calcium carrageenan trisodium phosphate sulfate (E407), sorbitol solution (E420), potassium sorbate (E202), sweet citrus berry flavour (containing propylene glycol (E1520), water, natural and artificial flavouring), antifoaming emulsion AF (containing polyethylene glycol (E1521), octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane and poly(oxi-1,2-ethanediyl), alpha-(1-oxooctadecyl)-omega-hydroxy).

Description of the appearance of Noxafil and contents of the pack
Noxafil gastro-resistant powder and solvent for oral suspension is supplied in a package containing:
Pack 1: The kit contains 8 single-dose child-resistant pouches (PET/aluminum/LLDPE), two 3 mL graduated tip syringes (green), two 10 mL graduated tip syringes (blue), two mixing containers, one 473 mL solvent bottle (HDPE) with a polypropylene (PP) closure and an induction-sealed aluminum liner, and a bottle adapter for the solvent bottle.
Pack 2: A box containing six 3 mL graduated tip syringes (green) and six 10 mL graduated tip syringes (blue).

Each single-dose sachet contains 300 mg of posaconazole, which must be suspended in 9 mL of solvent to obtain a total volume of 10 mL of suspension, resulting in a final concentration of approximately 30 mg per mL.

Marketing Authorization Holder and Manufacturer
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

България (Bulgaria)
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
[email protected]

Česká republika (Czech Republic)
Merck Sharp & Dohme s.r.o.
Tel: +420 277 050 000
[email protected]

Danmark (Denmark)
MSD Danmark ApS
Tlf.: +45 4482 4000
[email protected]

Deutschland (Germany)
MSD Sharp & Dohme GmbH
Tel.: +49 (0) 89 20 300 4500
[email protected]

Eesti (Estonia)
Merck Sharp & Dohme OÜ
Tel: +372 614 4200
[email protected]

Ελλάδα (Greece)
MSD Α.Φ.Ε.Ε.
Τηλ: +30 210 98 97 300
[email protected]

España (Spain)
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
[email protected]

France (France)
MSD France
Tél: +33 (0)1 80 46 40 40
[email protected]

Hrvatska (Croatia)
Merck Sharp & Dohme d.o.o.
Tel: +385 1 6611 333
[email protected]

Ísland (Iceland)
Vistor ehf.
Sími: +354 535 7000
[email protected]

Ireland (Ireland)
Merck Sharp & Dohme Ireland (Human Health) Limited
Tel: +353 (0)1 2998700
[email protected]

Italia (Italy)
MSD Italia S.r.l.
Tel: 800 23 99 89 (+39 06 361911)
[email protected]

Κύπρος (Cyprus)
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673 (+357 22866700)
[email protected]

Latvija (Latvia)
SIA Merck Sharp & Dohme Latvija
Tel.: +371 67025300
[email protected]

Lietuva (Lithuania)
UAB Merck Sharp & Dohme
Tel: +370 5 2780 247
[email protected]

Luxembourg/Luxemburg (Luxembourg)
MSD Belgium
Tél/Tel: +32(0)27766211
[email protected]

Magyarország (Hungary)
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
[email protected]

Malta (Malta)
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
[email protected]

Nederland (Netherlands)
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
[email protected]

Norge (Norway)
MSD (Norge) AS
Tlf: +47 32 20 73 00
[email protected]

Österreich (Austria)
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0)1 26 044
[email protected]

Polska (Poland)
MSD Polska Sp. z o.o.
Tel: +48 22 549 51 00
[email protected]

Portugal (Portugal)
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
[email protected]

România (Romania)
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
[email protected]

Slovenija (Slovenia)
Merck Sharp & Dohme, inovativna zdravila d.o.o.
Tel: +386 1 520 4201
[email protected]

Slovenská republika (Slovakia)
Merck Sharp & Dohme, s.r.o.
Tel: +421 2 58282010
[email protected]

Suomi/Finland (Finland)
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
[email protected]

Sverige (Sweden)
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
[email protected]

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu https://www.ema.europa.eu.

Instructions for Use

Noxafil 300 mg gastro-resistant powder and solvent for oral suspension

posaconazole

Instructions for Use

for those caring for children and adolescents

• Make sure you have read and understood these instructions for use.
• Bring this leaflet to your child’s medical appointments.

Before Starting

• Make sure you have read and understood all of these instructions before beginning. They may differ from
  those for medicines you have used previously.

• It is important to carry out all measurements carefully (Figure 1).

• Before administering Noxafil, check all 3 expiration dates. The expiration date is printed on the box (Figure 1), on the Noxafil sachets (Figure 2), and on the solvent (Figure 3).

• Do not open the Noxafil sachets until you are ready to mix the dose. Figure 3

Note: If you have any doubts, consult your doctor or pharmacist.
Before Starting

• The amount of Noxafil to administer depends on the child's weight. Your doctor will inform you of the correct dose to give your child. Make sure you attend all scheduled medical appointments so that dosing can be adjusted as your child grows.
• This leaflet explains how to:
  o Prepare Noxafil as a liquid
  o Measure the correct dose using an oral dosing syringe
  o Administer Noxafil to the child
  o Clean

Note: Position the child safely. You will need both hands to prepare Noxafil. Wash your hands with soap and water before preparing Noxafil.
Note before adding Noxafil: Make sure you and the child are ready. If you do not use Noxafil within 30 minutes, you must discard it and start again from the beginning.
Contents of the Kit

• Packaging • 2 mixing containers
• Instructions for use • 8 sachets (this leaflet) of Noxafil powder

• Package insert • Vial adapter

• 4 syringes (shown below) • Solvent vial for use with Noxafil

2 blue syringes (10 mL) 2 green syringes (3 mL)
The kit includes one extra mixing container and one extra set of syringes in case any component is missing or damaged.
Do not use damaged containers or syringes.
Familiarize Yourself with the Oral Dosing Syringes

• Before preparing a dose, review the parts of the syringe and how to use them.

• If you have any doubts about measuring with a syringe, consult your doctor or pharmacist.

• Make sure the plunger is fully pushed down into the barrel of the syringe before you begin measuring the dose.

• Check that the number on the graduated scale corresponds to the amount of solvent or Noxafil required.

• Make sure to follow the instructions in this leaflet to remove air bubbles from the syringe. Air bubbles can affect the amount of medicine the child receives.

Step 1. Prepare the Solvent
Note: Noxafil must be prepared using the provided solvent.
Do not mix Noxafil with milk, juice, or water.

When using the solvent for the first time:

• Open the vial and remove the safety seal. Use scissors if necessary.
• Place the vial adapter on top of the vial with the small opening facing upward.
• Push the vial adapter firmly down until fully seated.
• Once placed, the vial adapter remains on the vial.
• Replace the cap on the vial.

Step 2. Gather all necessary items and place them on a clean surface
Note: Position the child safely. You will need both hands to prepare Noxafil. Wash your hands with soap and water before preparing Noxafil.

The Noxafil box contains
a support for the mixing
container to help you tilt it
when measuring the dose.
Step 3. Add Noxafil to the mixing container
Note before adding Noxafil:
Make sure you and the child are ready. If you do not use
Noxafil within 30 minutes, you must discard it and start again from the beginning.

• Take 1 sachet of Noxafil and shake it to settle the powder at the bottom of the sachet. (Figure 1)

Figure 1

• Cut the sachet along the dotted line and pour all the powder into the mixing container. Make sure the sachet is completely empty. (Figure 2)

Figure 2
Step 4. Shake the solvent vial

• Shake the solvent well before each preparation of Noxafil.

Step 5. Fill the blue syringe with 9 mL of solvent

• Push the plunger of the blue syringe fully into the barrel.
• Remove the cap from the solvent vial.

• Insert the luer tip of the syringe into the vial adapter.
• With the syringe attached to the vial, turn the vial and syringe upside down. With the other hand, pull back the plunger to draw the solvent into the syringe.
• Stop when you reach the 9 mL mark.
• Turn the vial and syringe upright again and remove the syringe to check the measurement.

Step 6. Check for air bubbles

• Hold the syringe with the luer tip pointing upward. Tap it gently with your finger to move any air bubbles to the top.

• Slowly push the plunger to expel the air. (Figure 1)

Figure 1

• Recheck the solvent measurement
  in the syringe.
  If it is less than 9 mL, insert
  the luer tip back into the solvent
  and pull back the plunger until
  it reaches the 9 mL mark. (Figure 2)
  Figure 2
  Step 7. Add the 9 mL of solvent to Noxafil

• Add the 9 mL of solvent to the Noxafil powder in the mixing container by fully pushing the plunger.

Step 8. Mix Noxafil

• Close the lid of the mixing container.

• Shake the mixing container vigorously for 45 seconds to mix Noxafil. (Figure 1)
  Figure 1

• Check and ensure the powder is fully mixed. If not, shake the container again. Noxafil should appear cloudy and free of lumps. (Figure 2)

Figure 2
Step 9. Check the prescription

• Use the dose amount in 'mL' prescribed by the doctor.

Note: The dose may change at each doctor visit, so make sure you have the most up-to-date information. Attend all scheduled pediatric appointments to ensure the child receives the correct dose.
Step 10. Choose the correct syringe needed
Note: Use only the syringes provided in the kit.
Choose the correct syringe based on the prescribed dose:

From 1 mL From 3 mL
to 3 mL to 10 mL
Green Blue

• Then locate the mL mark on the syringe that corresponds to the prescribed dose.

Step 11. Measure Noxafil

Push the plunger fully
into the dosing syringe. (Figure 1)
Figure 1

• Tilt the mixing container in your hand or use the support provided in the Noxafil box. (Figure 2)

Figure 2

• Insert the luer tip of the dosing syringe into the lowest part of the mixing container with Noxafil and pull back the plunger. (Figure 3)
• Stop when you reach the line indicating the prescribed dose.

Figure 3
Note: You will not use all of the Noxafil.
Some residue will remain in the mixing container.
Step 12. Check for air bubbles

• Hold the syringe with the luer tip pointing upward. Tap it gently with your finger to move any air bubbles to the top.

• Slowly push the plunger to expel the air. (Figure 1) Figure 1

• Recheck the Noxafil measurement
  in the syringe. If it is less
  than the prescribed dose, insert
  the luer tip back into the mixing container with Noxafil and
  pull back the plunger until
  it reaches the correct dose mark. (Figure 2)
  Figure 2
  Step 13. Administer Noxafil to the child

• Gently place the syringe into the child’s mouth so that the luer tip touches the inside of the cheek.
• Slowly push the plunger to administer the dose of Noxafil. It is important that the child receives the full dose (a small amount remaining in the syringe tip is acceptable).

Note:

• If the child vomits or spits out the entire dose within 15 minutes of taking Noxafil, the dose may be repeated once. If this happens, consult your doctor or pharmacist.
• Use only the solvent provided in the kit. Do not mix Noxafil with milk, juice, or water.

Step 14. Clean the container and syringes
Note: The syringes and mixing containers must be reused. Do not discard the syringes and mixing containers provided until all Noxafil sachets have been used.
If syringes cannot be washed and reused, additional syringes are included in pack 2.

• Pour any remaining Noxafil from the
  mixing container into household waste.
  Do not pour it down the sink.

• Remove the plungers from all used syringes.

• Wash the syringes, plungers, and mixing container by hand with warm water and dish soap. Do not wash in a dishwasher.

• Rinse with water and air dry.
• Store all items in a clean, dry place.

Step 15. After all Noxafil sachets have been used

• After using the last Noxafil sachet in this box, there will be leftover solvent in the vial. Discard the remaining solvent and all kit components.