Posaconazole Accord 300 mg concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Posaconazol Accord 300 mg concentrate for solution for infusion EFG

posaconazole

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Posaconazol Accord is and what it is used for
2. What you need to know before using Posaconazol Accord
3. How to use Posaconazol Accord
4. Possible adverse effects
5. How to store Posaconazol Accord
6. Contents of the pack and other information

1. What Posaconazol Accord is and what it is used for

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

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

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

Posaconazole may be used in adults and children aged 2 years and older 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 leading to the 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.

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

• patients with a weakened immune system due to receiving chemotherapy for "acute myelogenous leukemia" (AML) or "myelodysplastic syndromes" (MDS);
• patients receiving "high-dose immunosuppressive therapy" following "hematopoietic stem cell transplantation" (HSCT).

2. What you need to know before using Posaconazol Accord

Do not use Posaconazol Accord if:

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

• you are taking: terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, any medicine containing "ergot alkaloids", such as ergotamine or dihydroergotamine, or a "statin", such as simvastatin, atorvastatin or lovastatin.

• you have just started taking venetoclax or your venetoclax dose is being gradually increased for the treatment of chronic lymphocytic leukemia (CLL).

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

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

Warnings and precautions

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

• you have 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 Posaconazol Accord.

• 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 problem with potassium, magnesium, or calcium levels in your blood.

• you are taking vincristine, vinblastine, or other "vinca alkaloids" (medicines used to treat cancer).

• you are taking venetoclax (a medicine used to treat cancer).

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before using Posaconazol Accord.

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

Children

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

Use of Posaconazol Accord 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 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 syndrome and mental illnesses)
• halofantrine (used to treat malaria)
• quinidine (used to treat heart rhythm disorders)

Posaconazol Accord 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. Posaconazol Accord can increase the levels of these medicines in the blood, which could cause 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 Posaconazol Accord if any of the above apply to you. If in doubt, consult your doctor or pharmacist before taking Posaconazol Accord.

Other medicines

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

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

The following medicines may reduce the effectiveness of Posaconazol Accord by decreasing 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 against bacterial infections).

Posaconazol Accord may possibly increase the risk of adverse effects of 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 called tretinoin (used to treat certain blood cancers).

If any of the above apply to you (or if you are unsure), consult your doctor or pharmacist before taking Posaconazol Accord.

Pregnancy and breastfeeding

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

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

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

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

Driving and using machines

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

Posaconazol Accord contains sodium

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

Consult your doctor or pharmacist if you require Posaconazol Accord 300 mg concentrate for solution for infusion or higher daily doses for a prolonged period, especially if you have been advised to follow a low-salt (sodium) diet.

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

This medicine contains 6680 mg of cyclodextrin per vial.

3. How to use Posaconazol Accord

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

The recommended dose for adults is 300 mg twice daily on the first day, followed by 300 mg once daily.

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

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 administered by a healthcare professional.

You will be given Posaconazol Accord:

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

The duration of treatment may depend on the type of infection you have or the period during which your immune system is not functioning properly, and may be individually adjusted for you by your doctor. Do not adjust your dose yourself before consulting your doctor, nor change your treatment regimen.

If you miss a dose of Posaconazol Accord

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

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

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 will experience them.

Serious adverse effects

Tell your doctor, pharmacist, or nurse immediately if you notice any of the following serious adverse effects; you may require 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 unwell without apparent reason, stomach problems, loss of appetite, or unusual tiredness or weakness, or increased 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, including symptoms such as confusion or weakness

• abnormal skin sensations such as numbness, tingling, itching, crawling sensations, prickling, 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 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, symptoms of which include headaches, feeling tired or dizzy, shortness of breath, paleness, and low haemoglobin levels detected in blood tests

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

• low levels of "leukocytes", a type of white blood cell (leukopenia), 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)

• neurological 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 oxygen supply to the spleen (splenic infarction), which may cause severe stomach pain

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

• high blood levels of creatinine, detected in blood tests

• cough, hiccups

• nosebleeds

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

• swelling of 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 difficulty 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 ache

• belching

• feeling restless

• swelling or pain at the injection site

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

• pneumonia, symptoms of which include shortness of breath and production of discoloured sputum

• high blood pressure in the blood vessels of the lungs (pulmonary hypertension), which may cause serious damage to the lungs and heart

• blood disorders such as unusual blood clotting or prolonged bleeding

• severe allergic reactions, including widespread rash with blisters and skin peeling

• mental problems, such as hearing voices or seeing things that are not there

• fainting

• problems with thinking or speaking, sudden uncontrolled movements, especially in the hands

• stroke, symptoms 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), symptoms of which include severe pain or swelling in the legs

• blood clots in the lungs (pulmonary embolism), symptoms of which include shortness of breath or pain when breathing

• bleeding in the stomach or intestines, symptoms of which include vomiting blood or blood in the stools

• intestinal blockage (intestinal obstruction), especially of the "ileum". This blockage prevents intestinal contents from passing through the colon, symptoms of which include bloating, vomiting, severe constipation, loss of appetite, and cramps

• "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 blood cells, white blood 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 sexual organ function

• hearing problems

• pseudoaldosteronism, which causes high blood pressure with low potassium levels (detected in blood tests)

Not known: frequency cannot be estimated from available data

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

• 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 or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Posaconazole Accord

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2 °C – 8 °C).
• From a microbiological standpoint, once reconstituted, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and will normally not exceed 24 hours at a temperature of 2 °C – 8 °C, unless reconstitution has taken place under controlled and validated aseptic conditions.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unused medicines and their containers. This will help protect the environment.

6. Contents of the container and other information

Composition of Posaconazol Accord

The active substance 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 injections.

Appearance of the product and contents of the container

Posaconazol Accord concentrate for infusion solution is a clear, colourless to yellow solution, free from visible particles. Colour variations within this range do not affect the quality of the product.

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

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6th floor, Barcelona,

08039 Barcelona, Spain

Manufacturer

Pharmadox Healthcare Ltd,

KW20A Kordin Industrial Park,

Paola, PLA3000

Malta

This medicine is authorised in the European Economic Area member states under the following names:

Netherlands: Posaconazol Accord
Germany: Posaconazol Accord 300 mg Konzentrat zur Herstellung einer Infusionslösung
Spain: Posaconazol Accord 300 mg concentrate for infusion solution EFG
France: Posaconazole Accord 300 mg, solution à diluer pour perfusion
Italy: Posaconazolo Vivanta

Date of latest revision of this leaflet: July 2022

Other sources of information

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

This information is intended for healthcare professionals only:

Instructions for administration of Posaconazol Accord 300 mg concentrate for infusion solution EFG

• Allow the refrigerated vial of Posaconazol Accord to reach room temperature.
• Aseptically transfer 16.7 ml of posaconazole to an intravenous infusion bag (or bottle) containing a compatible diluent (see list of diluents below), 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 via 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 concentrate for infusion solution must not be administered as an intravenous bolus.
• If a central venous catheter is not available, a single infusion may be administered via a peripheral venous catheter using an 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 administered through the same vein resulted in infusion site reactions (see section 4.8).

• Posaconazol Accord is for single use only.

The following medicines may be co-infused with posaconazole concentrate for infusion solution 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

Medicines not listed in this table must not be administered concomitantly with posaconazole through the same intravenous line (or cannula).

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

Any unused medicine and materials that have come into contact with it must be disposed of in accordance with local regulations.

Posaconazole must not be diluted with:

Ringer's lactate solution
5% glucose with Ringer's lactate solution
Sodium bicarbonate 4.2%

This medicine must not be mixed with any other medicinal products except those listed 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 KCl