Posaconazole accord

Package leaflet: Information for the user

Posaconazole Accord, 300 mg, concentrate for solution for infusion
Posaconazolum
Please read all of this leaflet carefully before this medicine is administered, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Posaconazole Accord is and what it is used for
2. Before you use Posaconazole Accord
3. How to use Posaconazole Accord
4. Possible side effects
5. How to store Posaconazole Accord
6. Contents of the pack and other information

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

Posaconazole Accord contains a substance called posaconazole, which belongs to a group of antifungal medicines. Posaconazole Accord is used to prevent and treat many types of fungal infections.
Posaconazole Accord works by killing or stopping the growth of fungi that can cause infections in humans.
Posaconazole Accord may be used in adults for the treatment of fungal infections caused by fungi of the genus Aspergillus.
Posaconazole Accord may be used in adults and children aged 2 years and older for the treatment of the following fungal infections:

• infections caused by species of the genus Aspergillus that do not respond to antifungal medicines, amphotericin B, or itraconazole, or when treatment with these medicines must be discontinued;
• infections caused by species of the genus Fusarium that do not respond to amphotericin B, or when treatment with amphotericin B must be discontinued;
• infections caused by fungi known as chromoblastomycosis and mycetoma that do not respond to itraconazole treatment, or when itraconazole treatment must be discontinued;
• infections caused by fungi known as Coccidioides that do not respond to one or more of the following medicines – amphotericin B, itraconazole, or fluconazole, or when treatment with these medicines must be discontinued.

Posaconazole Accord may also be used prophylactically to prevent fungal infections in adults and children aged 2 years and older who are at high risk of developing such infections, for example:

• in patients whose immune system is weakened due to chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome;
• in patients receiving high-dose immunosuppressive therapy after allogeneic haematopoietic stem cell transplantation.

2. Important information before using Posaconazole Accord

When not to use Posaconazole Accord:

• if the patient is allergic to posaconazole or any of the other ingredients of this medicine (listed in section 6);
• if the patient is taking terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, or any medicines containing ergot alkaloids such as ergotamine or dihydroergotamine, or statins such as simvastatin, atorvastatin or lovastatin;
• if the patient has started treatment with venetoclax or the dose of venetoclax is being gradually increased as part of therapy for chronic lymphocytic leukaemia (CLL).

Do not use Posaconazole Accord if any of the above situations apply to the patient. If in doubt, consult a doctor or pharmacist before using Posaconazole Accord.
More information on this, including information about other medicines that may interact with Posaconazole Accord, is provided below in the section “Posaconazole Accord and other medicines”.

Warnings and precautions

Before starting treatment with Posaconazole Accord, consult a doctor, pharmacist or nurse if:

• the patient has previously experienced an allergic reaction to another antifungal medicine such as ketoconazole, fluconazole, itraconazole or voriconazole;
• the patient currently has or has previously had liver problems. Blood tests may be required during treatment with Posaconazole Accord;
• the patient has QTc interval prolongation on ECG;
• the patient has been diagnosed with weakened heart muscle or heart failure;
• the patient has significant bradycardia (slow heart rate);
• the patient has cardiac arrhythmias;
• the patient has abnormal blood levels of potassium, magnesium or calcium;
• the patient is taking vincristine, vinblastine or other "vinca alkaloids" (medicines used in cancer treatment);
• the patient is taking venetoclax (a medicine used in the treatment of cancer).

During treatment, avoid exposure to sunlight. It is important to cover exposed skin areas with protective clothing and use a high sun protection factor (SPF) sunscreen, as increased sensitivity of the skin to ultraviolet (UV) radiation may occur.

If any of the above situations apply to the patient (or if in doubt), consult a doctor, pharmacist or nurse before using Posaconazole Accord.

Children

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

Posaconazole Accord and other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken or plans to take.

Do not use Posaconazole Accord if the patient is taking any of the following medicines:

• terfenadine (used to treat allergies),
• astemizole (used to treat allergies),
• cisapride (used to treat gastrointestinal discomfort),
• pimozide (used to treat symptoms of Tourette’s syndrome and psychiatric disorders),
• halofantrine (used to treat malaria),
• quinidine (used to treat heart rhythm disorders).

Posaconazole Accord may increase blood levels of the following medicines, leading to potentially serious heart rhythm disturbances:

• any medicines containing ergot alkaloids, such as ergotamine or dihydroergotamine, used to treat migraine headaches. Posaconazole Accord may increase blood levels of these medicines, which could lead to severely reduced blood flow to fingers or toes and subsequent tissue damage;
• statins such as simvastatin, atorvastatin or lovastatin, used to lower high cholesterol levels;
• venetoclax, used at the beginning of treatment for a type of cancer called chronic lymphocytic leukaemia (CLL).

Do not use Posaconazole Accord if any of the above situations apply to the patient. If in doubt, consult a doctor or pharmacist before taking Posaconazole Accord.

Other medicines

Review the above list of medicines that must not be used during treatment with Posaconazole Accord. In addition to the listed medicines, there are other medicines that may increase the risk of heart rhythm disturbances. This risk may be higher when these medicines are used together with Posaconazole Accord. Ensure that the treating doctor is informed about all medicines the patient is taking (both prescription and over-the-counter).

Some medicines may increase the risk of adverse effects of Posaconazole Accord by increasing its blood concentration.

The following medicines may reduce the blood concentration of Posaconazole Accord and thereby decrease its effectiveness:

• rifabutin and rifampicin (used to treat certain infections). Patients taking rifabutin should have blood tests 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 to prevent bacterial infections).

Posaconazole Accord may likely increase the risk of adverse effects of certain medicines by increasing their blood concentrations. These include:

• vincristine, vinblastine and other vinca alkaloids (used in cancer treatment);
• venetoclax (used in cancer treatment);
• cyclosporine (used during or after organ transplantation);
• tacrolimus and sirolimus (used during or after organ transplantation);
• rifabutin (used to treat certain infections);
• HIV protease inhibitors (including lopinavir and atazanavir taken 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 sulfonylurea derivatives (used to lower high blood sugar levels);
• all-trans retinoic acid (ATRA), also known as tretinoin (used to treat certain blood cancers).

If any of the above situations apply to the patient (or if in doubt), consult a doctor or pharmacist before taking Posaconazole Accord.

Pregnancy and breastfeeding

If the patient is pregnant or suspects she may be pregnant, she should inform her doctor before starting Posaconazole Accord.

Do not use Posaconazole Accord during pregnancy unless specifically advised by a doctor.

Women of childbearing potential should use effective contraception during treatment with Posaconazole Accord. If pregnancy occurs during treatment with Posaconazole Accord, inform the doctor immediately.

Do not breastfeed while taking Posaconazole Accord, as small amounts of the medicine may pass into breast milk.

Driving and operating machinery

While taking Posaconazole Accord, symptoms such as dizziness, drowsiness or blurred vision may occur, which could impair the ability to drive, use tools or operate machinery. In such cases, do not drive, use any tools or operate any machinery, and consult a doctor.

Posaconazole Accord contains sodium

The maximum recommended daily dose of this medicine contains 930 mg of sodium (from table salt). This corresponds to 47% of the maximum recommended daily dietary sodium intake for adults. Patients who take Posaconazole Accord more than once daily over a prolonged period, especially those on a low-salt (low-sodium) diet, should consult their doctor or pharmacist.

Posaconazole Accord contains cyclodextrin (sulfobutylether-beta-cyclodextrin sodium, SBECD)

This medicine contains 6680 mg of cyclodextrins per vial, equivalent to 95.43 mg/kg per day.

3. How to use Posaconazole Accord

This medicine should always be used exactly as your doctor or pharmacist has told you. If you are not sure,
ask your doctor or pharmacist.
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 aged 2 to below 18 years is 6 mg/kg body weight up to a maximum of 300 mg
twice daily on the first day, followed by 6 mg/kg body weight up to a maximum of 300 mg once daily.
Posaconazole Accord concentrate for solution for infusion will be diluted by a pharmacist or nurse to the appropriate concentration.
Posaconazole Accord concentrate for solution for infusion will always be prepared and administered to the patient by a healthcare professional.
The patient will receive Posaconazole Accord:

• through a plastic tube placed into the patient's vein (intravenous infusion),
• usually over approximately 90 minutes.

The duration of treatment may depend on the type of infection the patient has or how long the patient's immune system is not working properly, and may be adjusted by the doctor. The patient must not change the dose on their own or alter the treatment regimen without consulting their doctor.
Missed dose of Posaconazole Accord
Since this medicine will be administered under strict medical supervision, it is unlikely that a dose will be missed. However, if the patient thinks a dose may have been missed, they should inform their doctor or pharmacist.
When treatment with Posaconazole Accord is stopped by the doctor, the patient should not
experience any effects.
If you have any further questions about how to use this medicine, ask your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Serious adverse reactions
Immediately inform your doctor, pharmacist or nurse if any of the following serious adverse reactions occur,
as immediate medical attention may be required:

• nausea or vomiting, diarrhoea;
• symptoms of liver failure – these include yellowing of the skin or whites (sclera) of the eyes, abnormally dark urine or pale stools, unexplained nausea, stomach discomfort, loss of appetite, unusual tiredness or weakness, increased liver enzyme activity shown in blood tests;
• allergic reaction.

Other adverse reactions
If the patient experiences any of the adverse reactions listed below, inform the doctor,
pharmacist or nurse.
Common: may affect up to 1 in 10 people

• changes in blood electrolyte levels shown in blood tests – symptoms include
  confusion or weakness;
• abnormal skin sensation, including numbness, tingling, itching, goosebumps, pricking or burning sensations;
• swelling, redness and tenderness along the vein where the medicine was administered;
• headache;
• low potassium levels shown in blood tests;
• low magnesium levels shown in blood tests;
• high blood pressure;
• loss of appetite, stomach pain or upset stomach, gas, dry mouth, altered taste sensation;
• heartburn (a burning sensation in the chest up to the throat);
• decreased neutrophil count in blood tests – a type of white blood cell (neutropenia), which may increase susceptibility to infections;
• fever;
• feeling weak, dizziness, fatigue or drowsiness;
• rash;
• itching;
• constipation;
• discomfort in the rectum.

Uncommon: may affect up to 1 in 100 people

• anaemia – symptoms include headache, feeling tired or dizzy, shortness of breath or pale skin, and low haemoglobin levels shown in blood tests;
• decreased platelet count in blood tests (thrombocytopenia), which may lead to bleeding;
• decreased white blood cell count (leukopenia), which may increase susceptibility to infections;
• increased number of eosinophils – a type of white blood cell (eosinophilia), which may be associated with inflammatory conditions;
• inflammation of blood vessels;
• heart rhythm disorders;
• seizures;
• nerve damage (neuropathy);
• abnormal heart rhythm shown on ECG, palpitations, slow or rapid heartbeat, high or low blood pressure;
• low blood pressure;
• pancreatitis, which may cause severe abdominal pain;
• spleen infarction (splenic infarction) – this may cause severe abdominal pain;
• serious kidney function disorders – symptoms include reduced or increased urine output, or changes in urine colour;
• high creatinine levels in blood tests;
• cough, hiccups;
• nosebleeds;
• severe sharp chest pain occurring during breathing (pleuritic pain);
• swollen lymph nodes (lymphadenopathy);
• reduced sensation, especially of the skin;
• tremor;
• increased or decreased blood sugar levels;
• blurred vision, light sensitivity;
• hair loss (alopecia);
• mouth ulcers;
• chills, general malaise;
• pain, back or neck pain, arm or leg pain;
• fluid retention in the body (oedema);
• menstrual disorders (abnormal vaginal bleeding);
• difficulty falling asleep (insomnia);
• loss or disturbances of speech;
• swelling of the mouth;
• unusual dreams or sleep problems;
• coordination or balance disorders;
• mucosal inflammation;
• nasal congestion;
• breathing difficulties;
• chest discomfort;
• bloating;
• mild to severe nausea, vomiting, abdominal cramps and diarrhoea, usually caused by a virus, abdominal pain;
• belching;
• feeling of restlessness;
• inflammation or pain at the injection site.

Rare: may affect up to 1 in 1,000 people

• pneumonia – symptoms include shortness of breath and coughing up discoloured sputum;
• high blood pressure in the pulmonary blood vessels (pulmonary hypertension), which may lead to severe lung and heart damage;
• blood disorders, such as abnormal blood clotting or prolonged bleeding time;
• severe allergic reactions, including widespread blistering rash and skin peeling;
• psychiatric disorders, such as hearing voices and seeing things that are not there;
• fainting;
• problems with thinking or speaking, sudden uncontrolled limb movements, especially of the hands;
• stroke – symptoms include pain, weakness, numbness or tingling in limbs;
• appearance of a defect or dark spot (scotoma) in the visual field;
• heart failure or heart attack, which may lead to cardiac arrest and death, heart rhythm disorders causing sudden death;
• presence of blood clots in the blood vessels of the lower limbs (deep vein thrombosis) – symptoms include severe leg pain or swelling;
• presence of blood clots in the lung vessels (pulmonary embolism) – symptoms include shortness of breath or pain during breathing;
• bleeding from the stomach or intestines – symptoms include vomiting blood or blood in the stool;
• intestinal obstruction, especially of the small intestine. Obstruction prevents the movement of intestinal contents into the lower part of the digestive tract (large intestine). Symptoms include a feeling of bloating, vomiting, severe constipation, loss of appetite and intestinal cramps;
• haemolytic-uraemic syndrome, in which red blood cells break down (haemolysis). This may be accompanied by kidney failure;
• pancytopenia, i.e. decreased number of all blood cells (white and red blood cells and platelets) shown in blood tests;
• large purple bruises under the skin (thrombotic thrombocytopenic purpura);
• swelling of the face or tongue;
• depression;
• double vision;
• chest pain;
• adrenal gland dysfunction, which may cause weakness, fatigue, loss of appetite, skin pigmentation changes;
• pituitary gland dysfunction, which may cause decreased levels of certain hormones in the blood affecting the function of male or female reproductive organs;
• hearing problems;
• pseudoaldosteronism, resulting in high blood pressure with low potassium levels (visible in blood tests).

Frequency not known: frequency cannot be estimated from the available data

• some patients have also reported feeling disoriented after taking posaconazole;
• skin redness.

Contact your doctor, pharmacist or nurse if the patient experiences any of the
adverse reactions listed above.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Posaconazole Accord

• Keep the 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 specified month.
• Store in a refrigerator (2°C - 8°C).
• Chemical and physical stability has been demonstrated for 24 hours when stored at 2°C - 8°C.
• From a microbiological standpoint, the product should be used immediately after preparation. If the solution is not used immediately, it may be stored for up to 24 hours at a temperature of 2°C to 8°C, provided it was prepared under controlled and aseptic conditions.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the package and other information

What Posaconazole Accord contains
The active substance is posaconazole. One vial contains 300 mg of posaconazole.
Other components are: sulfobutylether beta-cyclodextrin sodium (see section 2), disodium edetate, hydrochloric acid and sodium hydroxide (for pH adjustment), water for injections.

What Posaconazole Accord looks like and contents of the pack
Posaconazole Accord is a concentrate for solution for infusion, which is a clear, colourless to yellow liquid, free from visible particles to the naked eye. Variation in the colour of the solution within this range does not affect the quality of the product.
Posaconazole Accord is available in a single-use 20 ml vial, closed with a rubber stopper and an aluminium cap with a blue flip-off seal.

Marketing Authorisation Holder and Importer
Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa 7 Street
02-677 Warsaw
Poland
Tel: +48 22 577 28 00

Importer
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Netherlands: Posaconazol Accordpharma
Czech Republic: Posaconazole Accord
Hungary: Posaconazol Accord
Poland: Posaconazole Accord
Romania: Posaconazol Accord Laboratories 300 mg concentrate pentru soluție perfuzabilă

The following information is intended solely for healthcare professionals:

Instructions for administration of Posaconazole Accord, 300 mg, concentrate for solution for infusion

• Remove the Posaconazole Accord vial from the refrigerator and allow it to reach room temperature.
• Depending on the final concentration to be achieved (not less than 1 mg/ml and not more than 2 mg/ml), under aseptic conditions, transfer 16.7 ml of posaconazole into an infusion bag (or infusion bottle) containing a compatible diluent (list of diluents is provided below) with a volume between 150 ml and 283 ml.
• Administer via central venous access through a central venous catheter or a peripherally inserted central catheter (PICC) as a slow intravenous infusion over approximately 90 minutes.
• Posaconazole Accord concentrate for solution for infusion must not be administered as a rapid intravenous injection.
• If a central venous catheter is not available, a single infusion with a volume allowing for a dilution of approximately 2 mg/ml may be administered via a peripheral intravenous catheter. When administered via a peripheral intravenous catheter, the infusion should last approximately 30 minutes.

Note: In clinical studies, repeated infusions administered peripherally through the same vein
led to infusion site reactions (see section 4.8).

• Posaconazole Accord is intended for single use only.

The following medicinal products may be co-administered via the same intravenous line (or lumen) simultaneously with Posaconazole Accord concentrate for solution for infusion:
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

Medicinal products not listed above must not be administered simultaneously with Posaconazole Accord through the same intravenous line (or lumen).
Posaconazole Accord concentrate for solution for infusion must be inspected visually for particulate matter prior to administration. The solution of Posaconazole Accord may be colorless or pale yellow. Variation in color within this range does not affect the quality of the product.
Any unused portions of the medicinal product or waste materials must be disposed of in accordance with local regulations.
Posaconazole Accord must not be diluted in:
Ringer's lactate solution
5% glucose solution with Ringer's lactate solution
4.2% sodium bicarbonate solution

This medicinal product must not be mixed with other medicinal products except those listed below:
5% glucose solution in water
0.9% sodium chloride solution
0.45% sodium chloride solution
5% glucose solution and 0.45% sodium chloride solution
5% glucose solution and 0.9% sodium chloride solution
5% glucose solution with 20 mEq KCl