POSACONAZOL ACCORD 300 MG CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Posaconazole Accord

Do not usePosaconazol Accordif:

• you are allergic to posaconazole or any of the other ingredients of this medicine (listed in section 6).

• you are taking: terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, any medicine that contains "ergot alkaloids", such as ergotamine or dihydroergotamine, or a "statin", such as simvastatin, atorvastatin or lovastatin.
• you have just started taking venetoclax or your dose of venetoclax is being slowly increased for the treatment of chronic lymphocytic leukaemia (CLL).

Do not use Posaconazol Accord if you are in any of the above situations. If in doubt, consult your doctor or pharmacist before taking Posaconazol Accord.

See the section “Using Posaconazol Accord with other medicines” below for information about other medicines that may interact with Posaconazol Accord.

Warnings and precautions

Consult your doctor, pharmacist or nurse before you start taking Posaconazol Accord if:

• you have had an allergic reaction to another antifungal medicine, such as ketoconazole, fluconazole, itraconazole or voriconazole.
• you have or have had liver problems. You may need to have blood tests while you are taking Posaconazol Accord.
• you have an abnormal heart rhythm (ECG) that shows a problem called prolonged QTc interval.
• you have weakness of the heart muscle or heart failure.
• you have a very slow heart rate.
• you have any abnormal heart rhythm.

• you have any problems with the amounts of potassium, magnesium or calcium in your blood.
• you are taking vincristine, vinblastine and other "vinca alkaloids" (medicines used to treat cancer).
• you are taking venetoclax (a medicine used to treat cancer).

If you are in any of the above situations (or in doubt), consult your doctor, pharmacist or nurse before using Posaconazol Accord.

You should avoid exposure to the sun while you are being treated. It is important to cover areas of skin exposed to the sun with protective clothing and to use a sunscreen with a high sun protection factor (SPF), as you may get more sensitive to the UV rays of the sun.

Children

Do not give Posaconazol Accord to children under 2 years of age.

Using Posaconazol Accord with other medicines

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

Do not take Posaconazol Accord 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 abnormal heart rhythms).

Posaconazol Accord may increase the amount of these medicines in your blood, which could cause serious changes in your heart rhythm:

• any medicine that contains "ergot alkaloids", such as ergotamine or dihydroergotamine used to treat migraines. Posaconazol Accord may increase the amount of these medicines in your blood, which could cause a serious decrease in blood flow to your fingers or toes and damage them.

• a "statin", such as simvastatin, atorvastatin or lovastatin used to treat high cholesterol.
• venetoclax when used at the start of treatment for a type of cancer, chronic lymphocytic leukaemia (CLL).

Do not take Posaconazol Accord if you are in any of the above situations. If in doubt, consult your doctor or pharmacist before taking Posaconazol Accord.

Other medicines

Consult the list provided above with the medicines that you should not use while taking Posaconazol Accord. In addition to the medicines mentioned above, there are other medicines that may cause problems with your heart rhythm, which may be greater when taken with posaconazole. Make sure to tell your doctor about all the medicines you are taking (with or without a prescription).

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

The following medicines may decrease the effectiveness of Posaconazol Accord by reducing its levels in your blood:

• rifabutin and rifampicin (used to treat certain infections). If you are already taking rifabutin, you will need to have a blood test, as well as be aware of some 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).

Posaconazol Accord may increase the risk of side effects of 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 transplants)
• tacrolimus and sirolimus (used during or after transplants)
• rifabutin (used to treat certain infections)
• medicines used to treat HIV called protease inhibitors (including lopinavir and atazanavir, which are given with ritonavir)
• midazolam, triazolam, alprazolam or other "benzodiazepines" (used as sedatives or muscle relaxants)
• diltiazem, verapamil, nifedipine, nisoldipine or other "calcium channel blockers" (used to treat high blood pressure)
• digoxin (used to treat heart failure)
• glipizide or other "sulfonylureas" (used to treat high blood sugar levels)
• all-trans retinoic acid (ATRA), also called tretinoin (used to treat some blood cancers).

If you are in any of the above situations (or in doubt), consult your doctor or pharmacist before taking Posaconazol Accord.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant or think you might be pregnant before you start taking Posaconazol Accord.

Do not use Posaconazol Accord if you are pregnant unless your doctor tells you to.

If you are a woman who can become pregnant, you must use effective contraception while you are using Posaconazol Accord. If you become pregnant while using Posaconazol Accord, contact your doctor immediately.

Do not breast-feed while you are using Posaconazol Accord, as small amounts may pass into breast milk.

Driving and using machines

You may feel dizzy, sleepy or have blurred vision while you are taking Posaconazol Accord, 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.

Posaconazol Accord contains sodium

The maximum recommended daily dose of this medicine contains 930 mg of sodium (found in table salt). This is equivalent to 46% of the maximum recommended daily intake of sodium for an adult.

Consult your doctor or pharmacist if you need Posaconazol Accord 300 mg concentrate for solution for infusion or more than one dose per day for a long time, especially if you have been advised to follow a low-salt diet.

Posaconazol Accord contains cyclodextrins (sulfobutyl ether beta-cyclodextrin sodium)

This medicine contains 6680 mg of cyclodextrin per vial.

3. How to use Posaconazol Accord

Follow exactly the instructions of administration of this medicine given to you by your doctor or pharmacist. If you are not sure, consult your doctor or pharmacist again.

The recommended dose for adults is 300 mg twice a day on the first day and then 300 mg once a day.

The recommended dose for children from 2 years to less than 18 years is 6 mg/kg up to a maximum of 300 mg twice a day on the first day and then 6 mg/kg up to a maximum of 300 mg once a day.

Your pharmacist or nurse will dilute Posaconazol Accord concentrate for solution for infusion to the correct concentration.

Posaconazol Accord concentrate for solution for infusion will always be prepared and given to you by a healthcare professional.

You will be given Posaconazol Accord:

• through a plastic tube inserted into a vein (intravenous infusion)
• usually over 90 minutes

The length of treatment may depend on the type of infection you have or the period of time during which your immune system is not working properly, and may be adjusted individually for you by your doctor. Do not change your dose yourself before consulting your doctor, or change your treatment schedule.

If you miss a dose ofPosaconazol Accord

Since this medicine is given under close medical supervision, it is unlikely that a dose will be missed. However, if you think that a dose may have been missed, inform your doctor or pharmacist.

When your doctor stops your treatment withPosaconazol Accordyou should not experience any effect.

If you have any further questions on 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 all people suffer from them.

Severe Adverse Effects

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

• nausea or vomiting (feeling or being sick), diarrhea

• signs of liver problems, including yellowing of the skin or the whites of the eyes, unusually dark urine or pale stools, feeling sick without apparent reason, stomach problems, loss of appetite or unusual fatigue or weakness, elevated liver enzymes detected in blood tests

• allergic reaction

Other Adverse Effects

Inform 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 salt levels detected in blood tests, whose signs include a feeling of confusion or weakness

• abnormal sensations in the skin, such as numbness, tingling, itching, crawling sensation, pinching, or burning
• swelling, redness, and pain along the vein where Posaconazol Accord was administered
• headache
• low potassium levels, detected in blood tests
• low magnesium levels, detected in blood tests
• high blood pressure

• loss of appetite, stomach pain or stomach discomfort, flatulence, dry mouth, changes in taste
• heartburn (a burning sensation in the chest that rises to the throat)
• low levels of "neutrophils", a type of white blood cell (neutropenia), which can make you more prone to infections and are detected in blood tests

• fever
• feeling of weakness, dizziness, fatigue, or drowsiness

• rash
• itching
• constipation
• rectal discomfort

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

• anemia, whose signs include headaches, feeling tired or dizzy, difficult breathing, or paleness and low hemoglobin levels detected in blood tests
• low platelet levels (thrombocytopenia), detected in blood tests. This can cause bleeding
• low levels of "leukocytes", a type of white blood cell (leukopenia), detected in blood tests. This can make you more susceptible to infections
• high levels of "eosinophils", a type of white blood cell (eosinophilia). This can appear if you have an inflammatory process
• inflammation of blood vessels
• heart rhythm problems
• seizures (convulsions)
• nerve damage (neuropathy)
• abnormal heart rhythm, detected in an electrocardiogram (ECG), palpitations, slow or fast heartbeat, high or low blood pressure
• low blood pressure
• inflammation of the pancreas (pancreatitis). This can cause severe stomach pain
• disruption of oxygen supply to the spleen (splenic infarction), which can cause severe stomach pain
• severe kidney problems, whose signs include increased or decreased urination with urine of a different color than usual
• high blood creatinine levels, detected in blood tests
• cough, hiccups
• nasal bleeding
• sharp and intense chest pain when breathing (pleuritic pain)
• inflammation of lymph nodes (lymphadenopathy)
• decreased sensitivity, especially in the skin
• tremors
• high or low blood sugar levels
• blurred vision, sensitivity to light
• hair loss (alopecia)
• mouth ulcers
• chills, feeling of discomfort
• pain, back or neck pain, pain in arms or legs
• fluid retention (edema)
• menstrual problems (abnormal vaginal bleeding)
• inability to sleep (insomnia)
• inability to speak totally or partially
• mouth swelling
• abnormal dreams or sleep problems
• coordination or balance problems
• mucosal inflammation
• nasal congestion
• breathing difficulties
• chest discomfort
• feeling bloated
• nausea, vomiting, cramps, and diarrhea from mild to severe, usually caused by a virus, stomach pain
• belching
• feeling of restlessness
• inflammation or pain at the injection site

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

• pneumonia, whose signs include shortness of breath and production of discolored mucus
• high blood pressure in the blood vessels of the lungs (pulmonary hypertension), which can cause serious damage to the lungs and heart
• blood problems such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including widespread skin rash with blisters and skin peeling
• mental problems, such as hearing voices or seeing things that are not there
• fainting
• problems thinking or speaking, sudden movements, especially in the hands, that cannot be controlled
• stroke, whose signs include pain, weakness, numbness, or tingling in the limbs
• presence of a blind spot or dark spot in the field of vision
• heart failure or heart attack, which can cause cardiac arrest and death, heart rhythm problems with sudden death
• blood clots in the legs (deep vein thrombosis), whose signs include intense pain or swelling of the legs
• blood clots in the lungs (pulmonary embolism), whose signs include shortness of breath or pain when breathing
• bleeding in the stomach or intestine, whose signs include vomiting blood or blood in the stool
• blockage of the intestine (intestinal obstruction), especially of the "ileum". This blockage prevents the contents of the intestine from passing through the colon and whose signs include feeling bloated, vomiting, severe constipation, loss of appetite, and cramps
• "hemolytic uremic syndrome" that occurs when there is destruction of red blood cells (hemolysis), which can occur with or without kidney failure
• "pancytopenia", low levels of all blood cells (red, white, and platelets), detected in blood tests
• large purple spots on the skin (thrombocytopenic purpura)
• inflammation of the face or tongue
• depression
• double vision
• breast pain
• inadequate functioning of the adrenal glands, which can cause weakness, fatigue, loss of appetite, skin discoloration
• inadequate functioning of the pituitary gland, which can cause low levels of certain hormones in the blood that affect the function of male or female sexual organs
• hearing problems
• pseudoaldosteronism, which causes high blood pressure with low potassium levels (appears in blood tests)

Unknown: the frequency cannot be estimated from the known data

• some patients have also reported feeling confused after using posaconazole.
• skin redness

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

Adverse Effect Reporting

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report it directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Posaconazol Accord

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date that appears on the label. The expiration date is the last day of the month indicated.
• Store in the refrigerator (between 2 °C - 8 °C).
• From a microbiological point of view, once mixed, the product must be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally will not exceed 24 hours at a temperature of 2 °C - 8 °C, unless the dilution has taken place in controlled and validated aseptic conditions.
• Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Posaconazol Accord

The active ingredient is posaconazole. Each vial contains 300 mg of posaconazole.

The other components are: sulfobutyl ether beta-cyclodextrin sodium, disodium edetate (see section 2), hydrochloric acid, sodium hydroxide, and water for injectable preparations.

Appearance of the Product and Package Contents

Posaconazol Accord concentrated solution for infusion is a clear, colorless to yellowish solution, free of visible particles. Color variations within this range do not affect the quality of the product.

This medicine is available in a single-use vial, 20 ml, closed with a rubber stopper and an aluminum seal, with a blue closure cap.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6a planta, Barcelona,

08039 Barcelona, Spain

Manufacturer

Pharmadox Healthcare Ltd,

KW20A Kordin Industrial Park,

Paola, PLA3000

Malta

This medicine is authorized in the Member States of the European Economic Area under the following names:

Netherlands Posaconazol AccordGermany Posaconazol Accord 300 mg Concentrate for Solution for InfusionSpain Posaconazol Accord 300 mg Concentrate for Solution for Infusion EFG

France Posaconazole Accord 300 mg, Solution to be Diluted for InfusionItaly Posaconazolo Vivanta

Date of the Last Revision of this Leaflet: July 2022

Other Sources of Information

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

Instructions for Administration of Posaconazol Accord 300 mg Concentrate for Solution for Infusion EFG

• Temper the refrigerated vial of Posaconazol Accord until it reaches room temperature.
• Transfer 16.7 ml of posaconazole aseptically to an intravenous infusion bag (or bottle) that contains a compatible mixing solvent (see below for the list of solvents) using a volume range of 150 ml to 283 ml depending on the final concentration to be obtained (not less than 1 mg/ml and not more than 2 mg/ml).
• Administer through a central venous line, including a central venous catheter or a peripherally inserted central catheter (PICC), by slow intravenous infusion over approximately 90 minutes.
• Posaconazol Accord concentrated solution for infusion should not be administered as a bolus.
• If a central venous catheter is not available, a single infusion can be administered through a peripheral venous catheter with the appropriate volume to obtain a dilution of approximately 2 mg/ml. In this case, the infusion should be administered over approximately 30 minutes.

Note: in clinical trials, multiple peripheral infusions performed through the same vein resulted in reactions at the infusion site (see section 4.8).

• Posaconazol Accord is for single use.

The following medicines can be infused at the same time as posaconazole concentrated solution for infusion and through the same intravenous line (or cannula):

Amikacin sulfate

Caspofungin

Ciprofloxacin

Daptomycin

Dobutamine hydrochloride

Famotidine

Filgrastim

Gentamicin sulfate

Hydromorphone hydrochloride

Levofloxacin

Lorazepam

Meropenem

Micafungin

Morphine sulfate

Norepinephrine bitartrate

Potassium chloride

Vancomycin hydrochloride

Do not administer any medicine with posaconazole through the same intravenous line (or cannula) that is not included in this table.

Before administration, the infusion solution should be visually inspected for the presence of particles. The Posaconazol Accord solution ranges from colorless to pale yellow. Color variations within this range do not affect the quality of the medicine.

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.

Posaconazol should not be diluted with:

Ringer's Lactate Solution

5% Glucose with Ringer's Lactate Solution

4.2% Sodium Bicarbonate

This medicine should not be mixed with others, except for those mentioned below:

5% Glucose in Water

0.9% Sodium Chloride

0.45% Sodium Chloride

5% Glucose and 0.45% Sodium Chloride

5% Glucose and 0.9% Sodium Chloride

5% Glucose and 20 mEq of KCl