Noxafil 100 mg gastro-resistant tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Noxafil 100mg gastro-resistant tablets

posaconazole

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Noxafil is and what it is used for

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

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

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

Noxafil can be used in adults and children aged 2 years and older who weigh more than 40 kg to treat the following types of fungal infections:

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

This medicine may also be used to prevent fungal infections in adults and children aged 2 years and older who weigh more than 40 kg and who are at high risk of developing a fungal infection, such as:

• patients who have a weakened immune system as a result of receiving chemotherapy for "acute myelogenous leukemia" (AML) or "myelodysplastic syndromes" (MDS);
• patients who are 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, cisapridine, pimozide, halofantrine, quinidine, any medicine containing "ergot alkaloids", such as ergotamine or dihydroergotamine, or a "statin", such as simvastatin, atorvastatin, or lovastatin.
• if you have just started taking venetoclax or your venetoclax dose is being gradually increased for the treatment of chronic lymphocytic leukemia (CLL).

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

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

Warnings and precautions

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

• you have ever had an allergic reaction to another antifungal medicine, such as ketoconazole, fluconazole, itraconazole, or voriconazole.
• you have or have previously had liver problems. You may need blood tests while taking this medicine.
• you develop severe diarrhea or vomiting, as these conditions may reduce the effectiveness of this medicine.
• you have a heart rhythm disorder (ECG) showing a problem called QTc interval prolongation.
• you have weakened heart muscle or heart failure.
• you have a very slow heartbeat.
• you have any heart rhythm disorder.
• you have any imbalance in blood levels of potassium, magnesium, or calcium.
• you are taking vincristine, vinblastine, or other "vinca alkaloids" (medicines used to treat cancer).
• you are taking venetoclax (a medicine used to treat cancer).

You should avoid exposure to sunlight during treatment. It is important to cover exposed skin areas with protective clothing and use sunscreen with a high sun protection factor (SPF), as increased sensitivity of the skin to UV rays from sunlight may occur.

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

If you develop severe diarrhea or vomiting (feel unwell) while taking Noxafil, contact your doctor, pharmacist, or nurse immediately, as this may prevent the medicine from working properly. For more information, see section 4.

Children

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

Taking Noxafil with other medicines

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

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

• terfenadine (used to treat allergies)
• astemizole (used to treat allergies)
• cisapride (used to treat stomach problems)
• pimozide (used to treat symptoms of Tourette's syndrome and mental illnesses)
• halofantrine (used to treat malaria)
• quinidine (used to treat heart rhythm disorders)

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

• any medicine containing "ergot alkaloids", such as ergotamine or dihydroergotamine, used to treat migraines. Noxafil can increase the levels of these medicines in the blood, which could lead to a serious reduction in blood flow to the fingers of the hands or feet and cause damage.

• a "statin", such as simvastatin, atorvastatin, or lovastatin, used to treat high cholesterol levels.

• venetoclax when used at the beginning of treatment for a type of cancer, chronic lymphocytic leukemia (CLL).

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

Other medicines

Refer to the list above of medicines you must not take while using Noxafil. In addition to the medicines mentioned above, there are other medicines that carry a risk of heart rhythm problems, and this risk 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 adverse effects from Noxafil by increasing the amount of Noxafil in the blood.

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

• rifabutin and rifampicin (used to treat certain infections). If you are already taking rifabutin, you will need to have a blood test and monitor for possible adverse effects of rifabutin.
• phenytoin, carbamazepine, phenobarbital, or primidone (used to treat or prevent seizures).
• efavirenz and fosamprenavir, used to treat HIV infection.
• flucloxacillin (an antibiotic used for bacterial infections).

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

• vincristine, vinblastine, and other "vinca alkaloids" (used to treat cancer)
• venetoclax (used to treat cancer)
• ciclosporin (used during or after organ transplants)
• tacrolimus and sirolimus (used during or after organ transplants)
• rifabutin (used to treat certain infections)
• medicines used to treat HIV called protease inhibitors (including lopinavir and atazanavir, 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 any of the above apply to you (or if you are in doubt), consult your doctor or pharmacist before taking Noxafil.

Pregnancy and breastfeeding

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

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

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

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

Driving and using machines

You may feel dizzy, drowsy, or experience blurred vision while taking Noxafil, which may affect your ability to drive or operate tools or machinery. If this occurs, do not drive or use any tools or machines and contact your doctor.

Noxafil contains sodium

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

3. How to take Noxafil

Do not switch interchangeably between Noxafil tablets and Noxafil oral suspension without consulting your doctor or pharmacist, as this may result in reduced effectiveness or an increased risk of adverse reactions.

Always follow exactly the instructions for administering this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

What dose to take

The recommended dose is 300 mg (three 100 mg tablets) twice daily 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 by your doctor. Do not adjust your dose yourself before consulting your doctor, nor change your treatment schedule.

How this medicine is administered

• Swallow the tablet whole with some 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 too much Noxafil, inform your doctor immediately or go to the hospital straight away.

If you forget to take Noxafil

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

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects

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

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

Other adverse effects

Tell your doctor, pharmacist, or nurse if you notice any of the following adverse effects:

Frequent: the following may affect up to 1 in 10 patients

• a change in blood electrolyte levels detected in blood tests, signs of which include confusion or weakness

• abnormal sensations in the skin, such as numbness, tingling, itching, crawling sensations, prickling, or burning

• headache

• low potassium levels, detected in blood tests

• low magnesium levels, detected in blood tests

• high blood pressure

• loss of appetite, stomach pain or discomfort, flatulence, dry mouth, changes in taste sensation

• heartburn (a burning sensation in the chest rising up to the throat)

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

• fever

• feeling weak, dizzy, tired, or drowsy

• rash

• itching

• constipation

• rectal discomfort

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

• anaemia, signs of which include headaches, feeling tired or dizzy, shortness of breath, paleness, and low haemoglobin levels detected in blood tests

• low platelet levels (thrombocytopenia), detected in blood tests. This may cause bleeding

• low levels of "leucocytes", a type of white blood cell (leucopenia), detected in blood tests. This may make you more susceptible to infections

• high levels of "eosinophils", a type of white blood cell (eosinophilia). This may occur if you have an inflammatory condition

• inflammation of blood vessels

• heart rhythm problems

• seizures (fits)

• nerve damage (neuropathy)

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

• low blood pressure

• inflammation of the pancreas (pancreatitis). This may cause severe stomach pain

• interruption of blood supply to the spleen (splenic infarction), which may cause severe stomach pain

• serious kidney problems, signs of which include increased or decreased urination with urine of unusual colour

• high blood creatinine levels, detected in blood tests

• cough, hiccups

• nosebleeds

• sharp, severe chest pain when breathing (pleuritic pain)

• swelling of the lymph nodes (lymphadenopathy)

• reduced sensation, especially in the skin

• tremors

• high or low blood sugar levels

• blurred vision, sensitivity to light

• hair loss (alopecia)

• mouth ulcers

• chills, general feeling of discomfort

• pain, back or neck pain, pain in arms or legs

• fluid retention (oedema)

• menstrual problems (abnormal vaginal bleeding)

• inability to sleep (insomnia)

• complete or partial inability to speak

• swelling of the mouth

• abnormal dreams or trouble sleeping

• problems with coordination or balance

• inflammation of the mucosa

• nasal congestion

• difficulty breathing

• chest discomfort

• feeling bloated

• nausea, vomiting, cramps, and mild to severe diarrhoea, usually caused by a virus, stomach pain

• belching

• feeling restless

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

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

Frequency not known: cannot be estimated from the available data

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

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Noxafil

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date stated on the blister pack after EXP. The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Noxafil

• The active substance in Noxafil is posaconazole. Each tablet contains 100 mg of posaconazole.
• The other components are hypromellose acetate succinate, microcrystalline cellulose, hydroxypropylcellulose (E-463), dicalcium silicate, sodium croscarmellose, magnesium stearate, polyvinyl alcohol, polyethylene glycol 3350, titanium dioxide (E-171), talc, yellow iron oxide (E-172).

Appearance of the product and contents of the pack

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

Only some pack sizes may be marketed.

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

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

Other sources of information

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