Noxafil 40 mg Oral Suspension

NOXAFIL contains a medicine called posaconazole. This belongs to a group of medicines called “antifungals”. NOXAFIL is used to prevent and treat many different fungal infections. NOXAFIL works by killing or stopping the growth of some types of fungi that can cause infections. NOXAFIL can be used to treat the following types of fungal infections in patients 13 years of age or older:

• Infections caused by fungi of the Aspergillus family that have not improved during treatment with the antifungal medicines amphotericin B, itraconazole or voriconazole, or when these
• Infections of the mouth or throat area caused by fungi of the Candida family that have not improved during treatment with the antifungal medicines amphotericin B, itraconazole or voriconazole, or when these medicines had to be stopped.
• Infections caused by fungi of the Fusarium family that have not improved during treatment of amphotericin B or other therapy, or when such therapy had to be stopped.
• Infections caused by fungi that cause the conditions known as zygomycosis, cryptococcosis, chromoblastomycosis and mycetoma, that have not improved during treatment with itraconazole, or other therapy, or when such therapy had to be stopped.
• Infections caused by the condition known as coccidioidomycosis.
• NOXAFIL can be used to prevent fungal infections in patients whose immune systems may be weakened due to other medicines or diseases.
• NOXAFIL Oral Suspension is also used for infections of the mouth or throat area (known as “thrush”) caused by fungi called Candida, which are initial infections.

Do not take NOXAFIL if:

• you are hypersensitive (allergic) to posaconazole or to any of the other ingredients of NOXAFIL
• you are taking medicines that contain ergot alkaloids (used to treat migraines). NOXAFIL can increase the blood levels of these medicines, which can lead to severe reductions in blood flow to some parts of the body and damage tissues
• you are taking any of the following medicines. NOXAFIL can increase the blood levels of these medicines, which can lead to very serious disturbances in heart rhythm
• terfenadine (used to treat allergies)
• astemizole (used to treat allergies)
• cisapride (used to treat stomach problems)
• pimozide (used to treat symptoms of Tourette’s disorder)
• quinidine (used to treat abnormal heart rhythms)
• If you are taking simvastatin, lovastatin, atorvastatin and some similar medicines (called HMG - CoA reductase inhibitors or statins) that are used to treat high cholesterol levels in the blood
• you are pregnant or breastfeeding.

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.
• have or have ever had liver problems. You may need to have blood tests while you are taking this medicine.
• develop severe diarrhoea or vomiting, as these conditions may limit the effectiveness of this medicine.
• have an abnormal heart rhythm tracing (ECG) that shows a problem called long QTc interval
• have a weakness of the heart muscle or heart failure
• have a very slow heartbeat
• have heart rhythm disturbance
• have any problem with potassium, magnesium or calcium levels in your blood
• are taking vincristine, vinblastine and other “vinca alkaloids” (medicines used to treat cancer).
• are taking venetoclax (a medicine used to treat cancer).

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before taking NOXAFIL. If you develop severe diarrhoea or vomiting (being sick) while taking NOXAFIL, talk to your doctor, pharmacist or nurse straight away, as this may stop it from working properly. See Section 4 for more information.

Children

Children under the age of 13 must not use NOXAFIL, unless instructed to do so by a doctor.

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 and mental illness)
• halofantrine (used to treat malaria)
• quinidine (used to treat abnormal heart rhythms).

NOXAFIL can increase the amount of these medicines in the blood which may lead to very serious changes to your heart rhythm:

• any medicines that contain “ergot alkaloids” such as ergotamine or dihydroergotamine used to treat migraines. NOXAFIL can increase the amount of these medicines in the blood which may lead to a severe decrease in blood flow to your fingers or toes and could cause damage to them.
• a “statin” such as simvastatin, atorvastatin or lovastatin used to treat high cholesterol.

Do not take NOXAFIL if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking this medicine.

Other medicines

Look at the list of medicines given above that must not be taken while you are taking NOXAFIL. In addition to the medicines named above there are other medicines that carry a risk of rhythm problems that may be greater when they are taken with NOXAFIL. Please make sure you tell your doctor about all the medicines you are taking (prescribed or non - prescribed). Certain medicines may increase the risk of side effects of NOXAFIL by increasing the amount of NOXAFIL in the blood. The following medicines may decrease 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 taking rifabutin, you will need a blood test and you will need to look out for some possible side effects of rifabutin.
• some medicines used to treat or prevent fits including; phenytoin, carbamazepine, phenobarbital or primidone).
• efavirenz and fosamprenavir used to treat HIV infection.

NOXAFIL may possibly increase the risk of side effects of some other medicines by increasing the amount of these medicines 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 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).

If any of the above apply to you (or you are not sure), talk to your doctor or pharmacist before taking NOXAFIL.

NOXAFIL 40 mg/mL Oral Suspension with food

To improve absorption of posaconazole, whenever possible it should be taken during or immediately after food or a nutritional drink (see section 3 ‘’How to take NOXAFIL’’). There is no information on the effect of alcohol on posaconazole.

Pregnancy and breastfeeding

Tell your doctor if you are or think you are pregnant before you start to take NOXAFIL. Do not take NOXAFIL if you are pregnant. If you are a woman who could become pregnant you should use effective contraception while you are taking this medicine. If you become pregnant while you are taking NOXAFIL, contact your doctor straight away. Do not breastfeed while taking NOXAFIL. This is because small amounts may pass into breast milk.

Driving and using machinery

You may feel dizzy, sleepy, or have blurred vision while taking NOXAFIL, which may affect your ability to drive or use tools or machines. If this happens, do not drive or use any tools or machines and contact your doctor.

NOXAFIL 40 mg/ml Oral Suspension contains glucose

NOXAFIL contains approximately 1,75 g of glucose per 5 mL of suspension. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Do not switch between taking NOXAFIL Tablets and NOXAFIL Oral Suspension without talking to your doctor or pharmacist because it may result in a lack of efficacy or an increased risk of adverse reactions. Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. Your doctor will monitor your response and condition to determine how long NOXAFIL needs to be given and whether any change is needed to your daily dose.

How much to take

NOXAFIL 40 mg/mL Oral Suspension

The table below shows the recommended dose and length of treatment which depend on the type of infection that you have and may be individually adapted for you by your doctor. Do not adapt your dose yourself before consulting your doctor or change your treatment regime.

Whenever possible you should take posaconazole during or immediately after food or a nutritional drink.

Indication

Recommended dose and length of treatment

• Treatment of refractory Fungal Infections (Invasive aspergillosis, Fusariosis, Chromoblastomycosis/Mycetoma, Coccidioidomycosis) The recommended dose is 200 mg (one 5 mL spoonful) taken four times daily. Alternatively, if recommended by your doctor, you may take 400 mg (two 5 mL spoonfuls) twice a day provided that you are able to take both doses during or after food or a nutritional drink.
• First time treatment of Thrush Oropharyngeal Candidiasis On the first day of treatment take 200 mg (one 5 mL spoonful) once. After the first day, take 100 mg (2,5 mL) once a day.
• Prevention of serious Fungal Infections Take 200 mg (one 5 mL spoonful) three times a day.
• Prophylaxis of Invasive Fungal Infections 200 mg (5 mL) three times a day. The duration of therapy is based on recovery from neutropenia or immunosuppression.
• Refractory Oropharyngeal or Oesophageal Candidiasis 400 mg (10 mL) twice a day. Duration of the therapy should be based on the severity of the patient’s underlying disease and clinical response.

If you take more NOXAFIL than you should

If you think that you may have taken too much NOXAFIL, talk to a doctor 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 it.
• However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule.
• Do not take a double dose to make up for a forgotten dose.

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

Not all side effects reported for NOXAFIL are included in this leaflet. Should your general health worsen of if you experience any untoward effects while taking NOXAFIL, please consult your healthcare provider for advice. NOXAFIL Oral Suspension can have side effects although not everybody gets them.

Serious side effects: Tell your doctor, pharmacist or nurse straight away if you notice any of the following serious side effects, you may need urgent medical treatment:

• nausea or vomit (feeling or being sick), diarrhoea,
• signs of liver problems, these include yellowing of your skin or whites of the eyes, unusually dark urine or pale faeces, feeling sick for no reason, stomach problems, loss of appetite or unusual tiredness or weakness, an increase in liver enzymes shown up in blood tests
• allergic reaction

Other side effects

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

Common side effects (occurring in at least 1 in 100 patients) are:

• a decrease in white blood cells (that can include the risk of infections)
• loss of appetite, electrolyte imbalance, low calcium
• headache, dizziness, numbness or tingling, sleepiness
• stomach pain, diarrhoea, upset stomach, wind, dry mouth, feeling or being sick, vomiting, constipation
• liver function tests that are higher than normal (including AST, ALT, alkaline phosphatase, GGT and bilirubin)
• rash, itching
• weakness, tiredness, fever

Other side effects that were related to treatment of NOXAFIL during clinical trials were: altered concentration of other medicinal products increased liver enzymes, nausea, rash and vomiting, excess bilirubin in the blood.

Uncommon and rare treatment related adverse events that were reported during clinical trials include: inability of the adrenal gland to function normally, allergic and/or hypersensitivity reactions. Some patients have also reported feeling confused after taking NOXAFIL, the frequency of this is not known.

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in tis leaflet. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of NOXAFIL Oral Suspension.

Store at or below 30 °C. Do not freeze. Store in the original container. Protect from light. Keep the container tightly closed. Store all medicines out of the reach of children. Do not use after the expiry date stated on the label. If you have any suspension left in the bottle more than 4 weeks after it was first opened, you should not use this medicine. Return all unused medicine to your pharmacist. Do not dispose of unused medicines in drains or sewerage systems (e.g. toilets).