Noxafil - Posaconazole uses, dose and side effects

Noxafil contains a drug called posaconazole. It belongs to a group of medicines called “antifungal medicines”. It is used to prevent or treat many different fungal infections.

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

Noxafil can be used in children from 2 years of age to treat the following types of fungal infections when other antifungal medicines have not worked or you have stopped taking them:

infection is caused by fungi of the family Aspergillus, which have not been improved by treatment with the antifungal drugs amphotericin B or itraconazole or when it has been necessary to discontinue treatment with these drugs.
infection is caused by fungi from the Fusarium family , which have not improved during treatment with amphotericin B or when it has been necessary to discontinue treatment with amphotericin B.
infections are caused by fungi that cause the conditions ‘chromoblastomycosis’ and ‘mycetoma’, which have not improved with treatment with itraconazole or when it has been necessary to discontinue treatment with itraconazole.
infection is caused by a fungus called Coccidioides , which has not been improved upon treatment with one or more of the medicines amphotericin B, itraconazole or fluconazole or when it has been necessary to discontinue treatment with these medicines.

This medicine can also be used to prevent fungal infections in children from 2 years of age who are at high risk of getting a fungal infection such as:

patients who have a weak immune system due to chemotherapy for “acute myeloid leukemia” (AML) or “myelodysplastic syndrome” (MDS).
Patients using high- dose treatment that inhibits the immune system following “haematopoietic stem cell transplantation” ( HSCT ).

What you need to know before you or your child take Noxafil

Do not take Noxafil

if you or your child are allergic to posaconazole or any of the other ingredients of this medicine (listed in section 6).
if you or your child are taking: terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine , medicines containing ‘ergot alkaloids’ such as ergotamine or dihydroergotamine, or a ‘statin’ such as simvastatin , atorvastatin or lovastatin.
if you have recently started taking venetoclax or if your dose of venetoclax is slowly being increased for the treatment of chronic lymphocytic leukemia ( CLL ).

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

See the section “Other medicines and Noxafil” below for more information including information about other medicines that may affect Noxafil.

Warnings and cautions

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

have had an allergic reaction to any other antifungal medicines such as ketoconazole , fluconazole , itraconazole and voriconazole.
have or have ever had liver problems. You may need to take blood samples while taking this medicine.
develops severe diarrhea or vomiting, as these conditions may limit the effect of this medicine.
has an abnormal heart rhythm, on examination ( ECG ), which indicates a problem called long QTc interval .
have a weakness in the heart muscle or heart failure .
have very slow heartbeats.
have some form of heart rhythm disorder.
have any kind of problem with the blood levels of potassium , magnesium or calcium .
take vincristine, vinblastine or other ‘vinca alkaloids’ (medicines used to treat cancer).
taking venetoclax (a medicine used to treat cancer).

If any of the above applies to you or your child (or you are not sure) talk to your doctor, pharmacist, or nurse before taking Noxafil.

If you develop severe diarrhea or vomiting (feeling unwell) while taking Noxafil, talk to a doctor, pharmacist, or nurse immediately as this may prevent it from working properly. See section 4 for more information.

Children

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

Other medicines and Noxafil

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

Do not take Noxafil if you or your child take any of the following:

terfenadine (used to treat allergies )
astemizole (used to treat allergies )
cisapride (used to treat stomach upset)
pimozide (used to treat symptoms of Tourette’s syndrome 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 can cause very serious disorders of your heart rhythm.

drugs that contain “ergot alkaloids” such as ergotamine or dihydroergotamine which are used to treat migraines . Noxafil can increase the amount of these drugs in the blood which can lead to a sharp decrease in blood flow to your fingers or toes and cause damage.
a “statin” such as simvastatin , atorvastatin or lovastatin used to treat high cholesterol .
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 or your child. If you are not sure, talk to your doctor or pharmacist before taking this medicine.

Other drugs

See the list above of medicines that must not be used while you or your child are taking Noxafil. In addition to the drugs mentioned above, other drugs carry a risk of arrhythmias that can be greater when taken with Noxafil. Tell your doctor about any medicines you or your child are taking (prescription or over-the-counter).

Some medicines may increase the risk of side effects from Noxafil by increasing the amount of Noxafil in your blood.

The following medicines may reduce the effect of Noxafil by reducing the amount of Noxafil in your blood:

rifabutin and rifampicin (used to treat certain infections ). If you are already being treated with rifabutin, your blood counts must be tested and certain probable side effects of rifabutin monitored.
phenytoin , carbamazepine, phenobarbital or primidone (used to treat or prevent epileptic seizures).
efavirenz and fosamprenavir used to treat HIV infection .

Noxafil may increase the risk of side effects from certain other medicines by increasing the amount of these medicines in your blood. These medicines include:

vincristine, vinblastine and other “vinca alkaloids” (used to treat cancer)
venetoclax (used to treat cancer)
ciclosporin (used during or after transplant surgery)
tacrolimus and sirolimus (used during or after transplant surgery)
rifabutin (used to treat certain infections )
antiviral medicines 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).
all ‑ trans retinoic acid (ATRA), also called tretinoin (used to treat certain types of blood cancer).

If any of the above applies to you or your child (or you are not sure) talk to your doctor or pharmacist before taking Noxafil.

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or think you may be pregnant before using Noxafil. Do not take Noxafil during pregnancy unless your doctor tells you to.

You should use effective contraception while taking this medicine if you are a woman and could become pregnant. Contact your doctor immediately if you become pregnant during treatment with Noxafil.

Do not breastfeed while you are being treated with Noxafil as small amounts may pass into breast milk.

Driving and using machines

You may feel dizzy, drowsy, or have blurred vision when taking Noxafil, which may affect your ability to drive or use machines. If this happens, do not drive or use machines and consult your doctor.

Noxafil contains

Noxafil contains methyl parahydroxybenzoate and propyl parahydroxybenzoate

This medicine contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate. May cause an allergic reaction (possibly delayed).

Noxafil contains sorbitol

This medicine contains 47 mg sorbitol (E420) per milliliter.

Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance, a rare inherited disease, talk to a doctor before you (or your child) take or receive this medicine.

Noxafil contains propylene glycol

This medicine contains 7 mg of propylene glycol (E1520) per milliliter.

Noxafil contains sodium

This medicine contains less than 1 mmol (23 mg) sodium per dose, ie essentially ‘sodium-free’. is next to “sodium-free”.

How to take Noxafil

Do not switch between Noxafil enteropowder and liquid for oral suspension and Noxafil oral suspension.

Always give this medicine to children according to the doctor’s or pharmacist’s instructions. If you are not sure, talk to your child’s doctor or pharmacist.

Read the instructions in the instructions for use on how to mix and give a dose of Noxafil. Save the instructions for use and follow the instructions each time you mix the medicine. Take the instructions for your child’s doctor’s visit with you.
Make sure that your doctor or pharmacist explains how the medicine is mixed and that the correct dose is given to your child.
The enteric powder for oral suspension must be mixed with the supplied diluent before use. You must give the medicine to your child within 30 minutes of mixing .
ONLY the diluent provided with the package may be used to complete Noxafil.
To ensure that the correct dose is given, ONLY use the notched syringes in the package to mix and give the medicine.
Make sure that the doctor’s instructions are followed. Your doctor will inform you if and when Noxafil is to be given to your child.

Noxafil enteric powder and liquid for oral suspension with food and drink

This medicine can be taken with or without food.

Dosage

The recommended dose for children from 2 years up to 18 years, weighing 10-40 kg is shown in the table below.

Body weight (kg)	Dose (volume)
10- <12 kg	90 mg (3 ml)
12- <17 kg	120 mg (4 ml)
17- <21 kg	150 mg (5 ml)
21- <26 kg	180 mg (6 ml)
26- <36 kg	210 mg (7 ml)
36-40 kg	240 mg (8 ml)

On day 1, the recommended dose is given twice.

After day 1, the recommended dose is given once daily.

For children weighing more than 40 kg, Noxafil tablets are recommended if they can swallow whole tablets.

The duration of treatment may depend on the type of infection you or your child has or how long the immune system is not working properly and may be individually tailored by your doctor. Do not change the dose or treatment schedule yourself until you have consulted your doctor.

If you or your child have taken too much Noxafil

If you think you or your child may have used too much Noxafil, talk to a doctor or go to the hospital immediately.

If you forget to take Noxafil

If you miss a dose , take it or give your child a dose as soon as you remember.
However, if it is almost time for your next dose , skip the missed dose and return 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 product, ask your doctor, pharmacist, or nurse.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects are

Talk to a doctor, pharmacist, or nurse immediately if you experience any of the following serious side effects – you or your child may need immediate medical attention:

nausea or vomiting (feeling or pronounced symptoms), diarrhea
signs of liver problems – characterized by yellowing of the skin or whites of the eyes, dark-colored urine or pale stools, feeling unwell for no reason, stomach problems, decreased appetite or abnormal fatigue or weakness, increase in liver enzymes detected by blood tests
allergic reaction

Other side effects are

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

Common (may affect up to 1 in 10 people)

a change in the salt levels in the blood detected by blood tests – characterized by the fact that you may feel confused or weak
an abnormal sensation in the skin, such as numbness, tingling, itching, crawling, stinging or burning sensation
headache
low potassium levels – detected by blood tests
low magnesium levels – detected by blood tests
high blood pressure
loss of appetite, abdominal pain or upset stomach, flatulence, dry mouth , taste changes
heartburn (a burning sensation in the chest that rises in the throat)
lower levels of “neutrophils”, a type of white blood cell ( neutropenia ) – which can increase the risk of infection and can be detected in blood tests
fever
weakness, dizziness, fatigue or drowsiness
rash
itching
constipation
rectal problems

Uncommon (may affect up to 1 in 100 people)

anemia – characterized by headache, fatigue or dizziness, shortness of breath or pallor and a low level of hemoglobin detected in blood tests
low level of platelets ( thrombocytopenia ) detected in blood tests – which can lead to bleeding
low level of “leukocytes”, a type of white blood cell ( leukopenia ) detected by blood tests – which may increase the risk of infection
high level of “eosinophils”, a type of white blood cell ( eosinophilia ) – which can occur in inflammation
inflammation of the blood vessels
heart rhythm problems
seizures (convulsions)
nerve damage ( neuropathy )
irregular heartbeat, detected by ECG , palpitations, slow or fast heartbeat, high or low blood pressure
low blood pressure
pancreatitis ( pancreatitis ) – which can cause intense abdominal pain
interrupted oxygen supply to the spleen (splenic infarction) – which can cause intense abdominal pain
severe kidney problems – characterized by increased or decreased urine output or discolored urine
high blood levels of creatinine – detected by blood tests
cough, hiccup
nosebleeds
severe sharp chest pain if inhaled (pleuritic pain)
enlarged lymph nodes ( lymphadenopathy )
decreased sensation especially in the skin
tremor
high or low blood sugar levels
blurred vision, photosensitivity
hair loss ( alopecia )
cold sores
tremors, general malaise
pain, back pain or neck pain, pain in arms or legs
accumulation of water in the body ( edema )
menstrual disorders (abnormal vaginal bleeding )
inability to sleep (insomnia)
completely or partially unable to speak
swelling in the mouth
abnormal dreams or difficulty sleeping
problems with coordination or balance
inflammation of the mucous membranes
nasal congestion
breathing difficulties
feeling of discomfort in the chest
feeling of bloating
Mild to severe nausea, vomiting, cramps and diarrhea, usually caused by a virus , abdominal pain
belching
feeling nervous

Rare (may affect up to 1 in 1,000 people)

pneumonia – characterized by a feeling of shortness of breath and discolored mucous vomiting
high blood pressure in blood vessels in the lungs (pulmonary hypertension) which can seriously damage the lungs and heart
problems with the blood such as unusual blood clotting or prolonged bleeding
severe allergic reactions including scattered blisters and peeling
mental problems such as hearing voices or seeing things that are not there
fainting
difficulty thinking or speaking, involuntary muscle twitching, especially in the hands
stroke – characterized by pain, weakness , numbness or tingling in the extremities
a blind or dark spot in the field of view
heart failure or heart attack which can lead to the heart stopping beating and death, disturbed heart rhythm with sudden death
blood clots in the legs (deep vein thrombosis ) – characterized by intense pain or swelling of the leg
blood clots in the lungs ( pulmonary embolism ) – characterized by shortness of breath or pain when breathing
bleeding in the stomach or intestines – characterized by bloody vomiting or blood in the stool
blockage of the intestine (intestinal obstruction) especially in the “ileum”, the lower part of the small intestine. The blockage prevents the contents of the intestine from passing to the large intestine, resulting in bloating, vomiting, severe constipation, loss of appetite and cramps
“Hemolytic uremic syndrome” with red blood cell dissolution ( hemolysis ) – which can occur with or without renal failure
“Pancytopenia” abnormal deficiency of all blood cells ( red blood cells , white blood cells and platelets ) detected by blood tests
large purple discolorations of the skin (thrombotic thrombocytopenic purpura)
swelling of the face or tongue
Depression
double vision
chest pain
impaired adrenal function – this can cause weakness, fatigue, loss of appetite, discoloration of the skin
impaired function of the pituitary gland – this can lead to decreased blood levels of hormones that affect the function of the male or female gonads
hearing problems
pseudoaldosteronism, which causes high blood pressure and low levels of potassium (shown in blood tests)

No known frequency (can not be calculated from the available data)

Some patients have also reported feeling confused after taking Noxafil.

Talk to your doctor, pharmacist, or nurse if you get any of the side effects listed above.

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 expiration date is the last day of the specified month.

This medicine does not require any special storage instructions.

Medicines or diluents should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Read the instructions in the instructions for use for the correct handling of leftover medicine.

Contents of the package and other information

Content declaration

The active substance is posaconazole. Each single-use sachet of oral powder for oral suspension is a white to a yellow powder containing 300 mg posaconazole.

The other ingredients are hypromellose acetate succinate.

The diluent contains the following: purified water, glycerol (E422), methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate, sodium dihydrogen phosphate monohydrate, citric acid, anhydrous (E330), xanthan gum (E415), sodium citrate (E415) sodium cirrose E407), sorbitol solution (E420), potassium sorbate (E202), flavoring, sweet berries and citrus (containing propylene glycol (E1520), water, natural and artificial flavors), antifoam Af emulsion (containing polyethylene glycol ( E1521 ), octamethylcyclopanethecanyloxane and poly (oxy-1,2-ethanediol), alpha- (1-oxooctadecyl)-omega.-hydroxy).

What the medicine looks like and contents of the pack

Noxafil enteric powder and liquid for oral suspension are supplied as a pack of:

Package 1: The pack contains 8 childproof disposable sachets (PET/aluminum / LLDPE), two 3 ml syringes (green) with slotted tips, two 10 ml syringes (blue) with slotted tips, two mixing cups, 473 ml diluent in a bottle ( HDPE) with polypropylene (PP) closure with foil closure and a bottle adapter for the diluent bottle.

Package 2: A carton of six 3 ml syringes (green) with slotted tips and six 10 ml syringes (blue) with slotted tips.

Each single-use sachet contains 300 mg posaconazole, which is mixed in 9 ml of diluent to obtain a total of 10 ml of suspension with a final concentration of approximately 30 mg per ml.

Marketing Authorization Holder and Manufacturer

Marketing Authorisation Holder

Merck Sharp & Dohme BV

Waarderweg 39

2031 BN Haarlem

Netherlands

Manufacturer

NV Organon

Kloosterstraat 6

5349 AB Oss