Prospect: information for the user

Posaconazol Accord 300 mg concentrate for solution for infusion EFG

posaconazol

Read this prospect carefully before starting tousethis medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.

• This medication has been prescribed to you alone, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they do not appear in this prospect. See section4.

1.What isPosaconazol Accordand for what it is used

2.What you need to know before starting to usePosaconazol Accord

3.How to usePosaconazol Accord

4.Possible adverse effects

5.Storage ofPosaconazol Accord

6. Contents of the package and additional information

Posaconazol Accordcontains a medicine called posaconazol, which belongs to a group of medicines called "antifungals”.Posaconazol Accordis used to prevent and treat many different types of fungal infections.

Posaconazolacts by killing or stopping the growth of some types of fungi that can cause infections.

Posaconazol can be used in adults to treat fungal infections caused by fungi of the familyAspergillus.

Posaconazolcan be used in adults and children aged 2 years or older to treat the following types of fungal infections:

• infections caused by fungi of the familyAspergillusthat have not improved during treatment with the antifungal medicines amphotericin B or itraconazole or when treatment with these medicines has had to be interrupted;
• infections caused by fungi of the familyFusariumthat have not improved during treatment with amphotericin B or when treatment with amphotericin B has had to be interrupted;
• infections caused by fungi that cause the diseases known as “chromoblastomycosis” and “mycetoma” that have not improved during treatment with itraconazole or when treatment with itraconazole has had to be interrupted;

• infections caused by a fungus calledCoccidioidesthat have not improved during treatment with one or more medicines, amphotericin B, itraconazole or fluconazole, or when treatment with these medicines has had to be interrupted.

Posaconazolcan also be used to prevent fungal infections in adults and children aged 2 years or older who are at high risk of contracting a fungal infection, such as:

• patients who have a weakened immune system as a result of having received chemotherapy for “acute myeloid leukemia” (AML) or “myelodysplastic syndromes” (MDS)

patients who are receiving “high doses of an immunosuppressive treatment” after a “hematopoietic stem cell transplant” (HSCT).

Do not usePosaconazol Accordif:

• You are allergic to posaconazol or any of the other components of this medication (listed in section6).

• You are taking: terfenadine, astemizol, cisaprida, pimozida, halofantrina, quinidina, any medication that contains "ergot alkaloids", such as ergotamine or dihydroergotamine, or a "statin", such as simvastatina, atorvastatina, or lovastatina.
• You have just started taking venetoclax or your dose of venetoclax is being gradually increased for the treatment of chronic lymphocytic leukemia (CLL).

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

See the section “Using Posaconazol Accord with other medications” later for information related to other medications that may interact with Posaconazol Accord.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to takePosaconazol Accordif:

• You have had an allergic reaction to another antifungal medication, such as ketoconazol, fluconazol, itraconazol, or voriconazol.
• You have or have had liver problems. You may need to have blood tests while takingPosaconazol Accord.
• You have a heart rhythm alteration (ECG) that shows a problem called prolongation of the QTc interval.
• You have heart muscle weakness or heart failure.
• You have a very slow heart rate.
• You have any heart rhythm alteration.

• You have any problem with the levels of potassium, magnesium, or calcium in your blood.
• You are taking vincristine, vinblastine, and other “vinca alkaloids” (medications used to treat cancer).
• You are taking venetoclax (a medication used to treat cancer).

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

You should avoid exposure to the sun while on treatment. It is essential to cover exposed skin areas with protective clothing and use high-factor sunscreen (SPF) as you may be more sensitive to UV rays from the sun.

Children

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

Using Posaconazol Accord with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Do not take Posaconazol Accord if you are taking any of the following medications:

• terfenadine (used to treat allergies)
• astemizol (used to treat allergies)
• cisaprida (used to treat stomach problems)
• pimozida (used to treat symptoms of Tourette's syndrome and mental disorders)
• halofantrina (used to treat malaria)
• quinidina (used to treat heart rhythm alterations).

Posaconazol Accordmay increase the amount of these medications in your blood, which could cause severe changes in your heart rhythm:

• any medication that contains "ergot alkaloids", such as ergotamine or dihydroergotamine used to treat migraines.Posaconazol Accordmay increase the amount of these medications in your blood, which could cause severe reduction of blood flow to your fingers or toes and damage them.

• a "statin", such as simvastatina, atorvastatina, or lovastatina used to treat high cholesterol levels.
• venetoclax when used at the start of treatment for a type of cancer, chronic lymphocytic leukemia (CLL).

Do not takePosaconazol Accordif you are in any of the above circumstances. If in doubt, consult your doctor or pharmacist before takingPosaconazol Accord.

Other medications

See the list provided earlier with the medications that you should not use while takingPosaconazol Accord. In addition to the medications mentioned earlier, there are other medications that present a risk of heart rhythm problems, which may be greater when taken with posaconazol. Ensure that you inform your doctor of all the medications you are taking (with or without a prescription).

Some medications may increase the risk of adverse effects ofPosaconazol Accordby increasing the amount ofPosaconazol Accordin your blood.

The following medications may reduce the effectiveness ofPosaconazol Accordby reducing its levels in your blood:

• rifabutina and rifampicina (used to treat certain infections). If you are already taking rifabutina, you will need to have blood tests, as well as be aware of some possible adverse effects of rifabutina.
• fenitoína, carbamazepina, fenobarbital, or primidona (used to treat or prevent seizures).
• efavirenz and fosamprenavir, used to treat HIV infection.
• flucloxacilina (antibiotic used to treat bacterial infections).

Posaconazol Accordmay possibly increase the risk of adverse effects of other medications by increasing the amount of these medications in your blood. These medications include:

• vincristine, vinblastine, and other “vinca alkaloids” (used to treat cancer)
• venetoclax (used to treat cancer)
• ciclosporina (used during or after transplants)
• tacrolimus and sirolimus (used during or after transplants)
• rifabutina (used to treat certain infections)
• medications 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, verapamilo, nifedipino, nisoldipino, or other "calcium channel blockers" (used to treat high blood pressure)
• digoxina (used to treat heart failure)
• glipizida or other "sulfonilureas" (used to treat high blood sugar levels)
• acid transretinoico (ATRA), also known as tretinoína (used to treat some blood cancers).

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

Pregnancy and breastfeeding

Inform your doctor if you are or think you may be pregnant before starting to takePosaconazol Accord.

Do not usePosaconazol Accordif you are pregnant, unless your doctor tells you to.

If you are a woman who may become pregnant, you should use effective contraceptive measures while usingPosaconazol Accord. If you become pregnant while usingPosaconazol Accord, contact your doctor immediately.

Do not breastfeed while usingPosaconazol Accord, as small amounts may pass into breast milk.

Driving and using machines

You may feel dizziness, drowsiness, or blurred vision while takingPosaconazol Accord, which may affect your ability to drive or use tools or machines. If this occurs, do not drive or use any tools or machines and contact your doctor.

Posaconazol Accord contains sodium

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

Consult your doctor or pharmacist if you need Posaconazol Accord 300mg concentrate for solution for infusion or more daily doses for a prolonged period, especially if you have been recommended a low-sodium diet.

Posaconazol Accordcontains cyclodextrins (sulfobutyl ether beta-cyclodextrin sodium)

This medication contains 6680 mg of cyclodextrin per vial.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose for adults is 300 mg twice a day on the first day and subsequently 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 subsequently 6 mg/kg up to a maximum of 300 mg once a day.

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

Always have a healthcare professional prepare and administer Posaconazol Accord concentrate for infusion solution.

You will be administered Posaconazol Accord:

• through a plastic tube placed in your vein (intravenous infusion)
• usually for 90 minutes

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

If you forgot a dose of Posaconazol Accord

Since this medication is administered under strict medical supervision, it is unlikely that a dose will be missed. However, if you think you may have forgotten to administer a dose, inform your doctor or pharmacist.

When your doctor stops treatment with Posaconazol Accord, you should not experience any effects.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

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

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

• signs of liver problems, which include yellowing of the skin or the white of the eyes, dark or unusual urine, pale stools, feeling sick without apparent reason, stomach problems, loss of appetite or unusual weakness or fatigue, an increase in liver enzymes detected in blood tests

• allergic reaction

Other side effects

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

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

• an abnormal change in blood sodium levels detected in blood tests, whose signs include confusion or weakness

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

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

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

• eruption
• itching
• constipation
• rectal discomfort

Uncommon: 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 levels of platelets (thrombocytopenia), detected in blood tests. This may cause bleeding
• low levels of "leukocytes", 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 appear if you have an inflammatory process
• inflammation of blood vessels
• problems with heart rhythm
• seizures (convulsions)
• neurological damage (neuropathy)
• abnormal heart rhythm, detected in an electrocardiogram (ECG), palpitations, slow or fast heart rate, high or low blood pressure
• low blood pressure
• inflammation of the pancreas (pancreatitis). This may cause severe stomach pain
• interruption of oxygen supply to the spleen (splenic infarction), which may cause severe stomach pain
• serious kidney problems, whose signs include increased or decreased urination with urine that is a different color from usual
• high levels of creatinine in the blood 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, light sensitivity
• hair loss (alopecia)
• mouth ulcers
• chills, feeling of habitual discomfort
• back or neck pain, arm or leg pain
• fluid retention (edema)
• menstrual problems (abnormal vaginal bleeding)
• insomnia (inability to sleep)
• total or partial inability to speak
• swelling of the mouth
• abnormal dreams or sleep problems
• coordination or balance problems
• inflammation of the mucosa
• nasal congestion
• difficulty breathing
• chest discomfort
• feeling bloated
• nausea, vomiting, cramps and diarrhea of mild to severe, usually caused by a virus, stomach pain
• belching
• sensation of anxiety
• inflammation or pain at the injection site

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

• pneumonia, whose signs include feeling short of breath and production of discolored mucus
• high blood pressure in the blood vessels of the lungs (pulmonary hypertension), which may cause severe damage to the lungs and heart
• blood clotting problems, such as unusual blood clotting or prolonged bleeding
• severe allergic reactions, including widespread skin rash with blisters and skin exfoliation
• mental problems, such as hearing voices or seeing things that are not there
• syncope (fainting)
• problems with thinking or speaking, sudden movements, especially in the hands, that you cannot control
• stroke, whose signs include pain, weakness, numbness or tingling in the extremities
• presence of a blind spot or dark spot in the field of vision
• heart failure or heart attack, which may cause cardiac arrest and death, problems with heart rhythm 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 feeling short of breath or chest pain
• bleeding in the stomach or intestines, whose signs include vomiting blood or blood in the stool
• 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 abdominal cramps
• "uricemic hemolytic syndrome" that appears when there is destruction of red blood cells (hemolysis), which may occur with or without kidney failure
• "pancytopenia", low levels of all blood cells (red, white and platelets), detected in blood tests
• purple and large spots on the skin (thrombotic thrombocytopenic purpura)
• inflammation of the face or tongue
• depression
• double vision
• breast pain
• inadequate functioning of the adrenal glands, which may cause weakness, fatigue, loss of appetite, skin discoloration
• inadequate functioning of the pituitary gland, which may cause low levels of certain hormones in the blood that affect the function of male or female sex 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 side effects described above.

Reporting side effects

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

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the label. The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2 °C – 8 °C).
• From a microbiological standpoint, once mixed, the product must be used immediately. If not used immediately, storage times and conditions before use are the responsibility of the user and will normally not last more than 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 disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Posaconazole Accord Composition

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

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

Appearance of the product and contents of the package

Posaconazole Accord concentrated solution for infusion is a transparent, colorless to yellow solution, free of visible particles. Variations in color 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 responsible manufacturer

Marketing authorization holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6th floor, Barcelona,

08039 Barcelona, Spain

Responsible manufacturer

Pharmadox Healthcare Ltd,

KW20A Kordin Industrial Park,

Paola, PLA3000

Malta

This medicine is authorized in the member states of the European Economic Area with the following names:

Netherlands Posaconazol Accord
Germany Posaconazol Accord 300 mg Concentrate for the preparation of an infusion solution
Spain Posaconazol Accord 300 mg concentrated solution for infusion EFG

France Posaconazole Accord 300 mg, solution to be diluted for infusion
Italy Posaconazolo Vivanta

Last review date of this leaflet: July 2022

Other sources of information

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Administration instructions for Posaconazole Accord 300 mg concentrated solution for infusion EFG

• Refrigerate the Posaconazole Accord vial until it reaches room temperature.
• Transfer 16.7 ml of posaconazole aseptically to an intravenous infusion bag (or flask) containing a compatible diluent (see below for the list of diluents) using a volume range of 150 ml to 283 ml depending on the desired final concentration (not less than 1 mg/ml and not more than 2 mg/ml).
• Administer through a central venous route, including a central venous catheter or a peripheral central catheter (PCC), via a slow intravenous infusion over approximately 90 minutes.
• Posaconazole 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 achieve 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 through the same vein resulted in the appearance of reactions at the infusion site (see section 4.8).

• Posaconazole Accord is for single use.

The following medications can be infused simultaneously with posaconazole concentrated solution for infusion and through the same intravenous route (or cannula):

No other medication should be administered simultaneously with posaconazole through the same intravenous route (or cannula).

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

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

Posaconazole should not be diluted with:

This medicine should not be mixed with other medications, except for the following: