Posaconazole altan

Patient Information Leaflet

Pozakonazol Altan, 300 mg, concentrate for solution for infusion
Posaconazolum
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not share it with others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Pozakonazol Altan is and what it is used for

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

• infections caused by species of the genus Aspergillus that do not respond to antifungal treatments, 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 treatment, or when amphotericin B treatment must be discontinued;
• infections caused by fungi known as "chromoblastomycosis" and "phaeohyphomycosis" 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.

Pozakonazol Altan 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 with weakened immune systems due to chemotherapy for "acute myeloid leukemia" (AML) or "myelodysplastic syndrome" (MDS);
• in patients receiving high-dose immunosuppressive therapy after hematopoietic stem cell transplantation (HSCT).

2. Important information before using Pozakonazol Altan

When not to use Pozakonazol Altan:

• 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 just 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 Pozakonazol Altan if any of the above situations apply to the patient.
If in doubt, consult a doctor or pharmacist before using Pozakonazol Altan.
More information on this, including details about other medicines that may interact with Pozakonazol Altan, is provided below in the section "Pozakonazol Altan and other medicines".

Warnings and precautions

Before starting treatment with Pozakonazol Altan, consult your 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 disease. Blood tests may be necessary during treatment with Pozakonazol Altan;
• the patient has ECG abnormalities indicating QTc interval prolongation;
• the patient has been diagnosed with weakened heart muscle or heart failure;
• the patient has significant slowing of heart rate;
• the patient has heart rhythm disorders;
• 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 Pozakonazol Altan.

Children

Pozakonazol Altan must not be given to children under 2 years of age.

Pozakonazol Altan 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 Pozakonazol Altan 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 problems),
• pimozide (used to treat symptoms of Tourette’s syndrome and psychiatric disorders),
• halofantrine (used to treat malaria),
• quinidine (used to treat heart rhythm disorders).

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

• any medicines containing "ergot alkaloids" such as ergotamine or dihydroergotamine, used to treat migraine headaches. Pozakonazol Altan 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 Pozakonazol Altan if any of the above situations apply to the patient.
If in doubt, consult a doctor or pharmacist before taking Pozakonazol Altan.

Other medicines

Please review the list above of medicines that must not be used during treatment with Pozakonazol Altan. In addition to the medicines listed above, there are other medicines associated with a risk of heart rhythm disturbances, and this risk may be increased when used together with Pozakonazol Altan. 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 Pozakonazol Altan by increasing its blood concentration.

The following medicines may reduce the blood concentration of Pozakonazol Altan and thus decrease its effectiveness:

• rifabutin and rifampicin (used to treat certain infections). Patients taking rifabutin should undergo blood tests and monitor for possible adverse effects of rifabutin;
• certain antiepileptic medicines, including phenytoin, carbamazepine, phenobarbital, or primidone;
• efavirenz and fosamprenavir (used to treat HIV infection);
• flucloxacillin (an antibiotic used to prevent bacterial infections).

Pozakonazol Altan may likely increase the risk of adverse effects of certain medicines by increasing their blood concentration. 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 together 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 Pozakonazol Altan.

Pregnancy and breastfeeding

If the patient is pregnant or suspects she may be pregnant, she should inform her doctor before starting treatment with Pozakonazol Altan.
Do not use Pozakonazol Altan during pregnancy unless specifically advised by a doctor.
Women of childbearing potential should use an effective method of contraception during treatment with Pozakonazol Altan. If pregnancy occurs during treatment with Pozakonazol Altan, the patient should inform her doctor immediately.

Do not breastfeed during treatment with Pozakonazol Altan, as small amounts of the medicine may pass into human milk.

Driving and operating machinery

While taking Pozakonazol Altan, 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 tools, or operate machinery, and consult a doctor.

Pozakonazol Altan contains sodium

This medicine contains 477 mg of sodium (the main component of table salt) in one dose.
This corresponds to 23.8% of the maximum recommended daily dietary sodium intake for adults.
If long-term daily use of Pozakonazol Altan 300 mg concentrate for solution for infusion is required, consult a pharmacist or doctor, especially if the patient has been advised to follow a low-salt (low-sodium) diet.

Pozakonazol Altan contains cyclodextrin

This medicine contains 6680 mg of cyclodextrin in each vial, equivalent to 6680 mg/16.7 mL.

3. How to use Pozakonazol Altan

This medicine should always be used as directed by a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.

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

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 on the first day, followed by 6 mg/kg body weight up to a maximum of 300 mg once daily thereafter.

Pozakonazol Altan in the form of concentrate for solution for infusion will be diluted by a pharmacist or nurse to the appropriate concentration.

Pozakonazol Altan in the form of concentrate for solution for infusion will always be prepared and administered to the patient by a qualified healthcare professional.

The patient will receive Pozakonazol Altan:

• 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 present or how long the patient's immune system remains impaired, and may be individually adjusted by the doctor.

The patient should not change the dose or alter the treatment regimen without consulting a doctor.

Missed dose of Pozakonazol Altan
Since this medicine will be administered under strict medical supervision, it is unlikely that a dose will be missed. However, if the patient suspects that a dose has been missed, they should inform the doctor or pharmacist.

When treatment with Pozakonazol Altan is discontinued by the doctor, the patient should not experience any effects.

If there are any further doubts regarding the use of this medicine, consult a 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 a doctor, pharmacist, or nurse if any of the following serious adverse reactions occur,
as immediate medical assistance may be required:

• nausea or vomiting, diarrhoea;
• signs of liver failure such as yellowing of the skin or whites of the eyes (jaundice), abnormally dark-coloured 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 occur in up to 1 in 10 people

• changes in blood electrolyte levels detected in blood tests, including confusion or weakness;
• abnormal skin sensations, including numbness, tingling, itching, goosebumps, pricking or burning;
• swelling, redness, and tenderness along the vein where Pozakonazol Altan 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 indigestion, gas, dry mouth, taste disturbances;
• heartburn (a burning sensation in the chest up to the throat);
• decreased number of neutrophils (a type of white blood cell) detected in blood tests (neutropenia), which may increase susceptibility to infections;
• fever;
• feeling of weakness, dizziness, fatigue, or drowsiness;
• rash;
• itching;
• constipation;
• discomfort in the rectum.

Uncommon: may occur in up to 1 in 100 people

• anaemia – symptoms include headache, feeling tired or dizzy, shortness of breath, or pale skin, and low haemoglobin levels detected in blood tests;
• decreased number of platelets detected in blood tests (thrombocytopenia), which may lead to bleeding;
• decreased number of leukocytes (a type of white blood cell) detected in blood tests (leukopenia), which may increase susceptibility to infections;
• increased number of eosinophils (a type of white blood cell) detected in blood tests (eosinophilia), which may be associated with inflammatory conditions;
• inflammation of blood vessels;
• heart rhythm disorders;
• seizures;
• nerve damage (neuropathy);
• abnormal heart rhythm detected on ECG, palpitations, slow or rapid heartbeat, high or low blood pressure;
• low blood pressure;
• pancreatitis, which may cause severe abdominal pain;
• splenic infarction (spleen tissue death due to lack of oxygen) – 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 urine detected in blood tests;
• cough, hiccups;
• nosebleeds;
• severe, sharp chest pain occurring during breathing (pleuritic pain);
• enlarged lymph nodes (lymphadenopathy);
• reduced sensation, especially of the skin;
• tremor;
• increased or decreased blood sugar levels;
• blurred vision, light sensitivity;
• hair loss (alopecia);
• mouth ulceration;
• chills, general malaise;
• pain, back or neck pain, arm or leg pain;
• fluid retention (oedema);
• menstrual disorders (abnormal vaginal bleeding);
• difficulty falling asleep (insomnia);
• loss or disturbances of speech;
• swelling of the mouth;
• strange 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 shaky;
• inflammation or pain at the injection site.

Rare: may occur in up to 1 in 1000 people

• pneumonia – symptoms may 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 real;
• fainting;
• problems with thinking or speaking, sudden uncontrolled movements of limbs, especially hands;
• stroke – symptoms may include pain, weakness, numbness or tingling in limbs;
• appearance of a blind spot 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 may include severe leg pain or swelling;
• presence of blood clots in the blood vessels of the lungs (pulmonary embolism) – symptoms may include shortness of breath or pain during breathing;
• bleeding from the stomach or intestines – symptoms may include vomiting blood or presence of blood in stool;
• intestinal obstruction, particularly of the "twisted intestine" (volvulus). Obstruction prevents the movement of intestinal contents into the lower part of the digestive tract (large intestine). Symptoms may include bloating, vomiting, severe constipation, loss of appetite, and intestinal cramps;
• "haemolytic-uraemic syndrome", involving destruction of red blood cells (haemolysis), which may be accompanied by kidney failure;
• "pancytopenia", i.e. decreased number of all blood cells (white blood cells, red blood cells, and platelets) detected 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, changes in skin pigmentation;
• pituitary gland dysfunction, which may cause reduced levels of certain hormones in the blood affecting male or female reproductive organs;
• hearing problems;
• pseudoaldosteronism, causing high blood pressure with low potassium levels (detected in blood tests).

Frequency not known: frequency cannot be estimated from available data

• some patients have reported feeling disoriented after taking Pozakonazol Altan;
• skin redness.

Inform a 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 reactions not listed in
this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C
02-222 Warsaw
Phone: +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 authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Pozakonazol Altan

Keep this medicine out of 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.
There are no special storage requirements for this medicine.
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, unless the solution has been prepared under controlled and validated aseptic conditions.
This medicinal product is for single use only, and any unused solution should be discarded.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Pozakonazol Altan contains
The active substance is posaconazole. One vial contains 300 mg of posaconazole.
The other ingredients are: sulfobutylether beta-cyclodextrin sodium, disodium edetate, hydrochloric acid (1 mol/L), sodium hydroxide, water for injections.

What Pozakonazol Altan looks like and contents of the pack
Pozakonazol Altan is a concentrate for solution for infusion, which is a transparent liquid, colourless to pale yellow.
Colour variations within this range do not affect the quality of the product.
Pozakonazol Altan is available in a 20 mL type I amber glass vial with a bromobutyl rubber stopper and aluminium seal, containing 16.7 mL of solution.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Altan Pharmaceuticals, S.A.
C/ Cólquide Nº 6, Portal 2, 1ª Planta, Oficina F. Edificio Prisma
Las Rozas, 28230 Madrid
Spain

Manufacturer:
Altan Pharmaceuticals S.A.
Polígono Industrial de Bernedo, s/n
01118 Bernedo, Álava
Spain

This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria: Posaconazol Altan 300 mg Konzentrat zur Herstellung einer Infusionslösung
Spain: Posaconazol Altan 300 mg concentrado para solución para perfusión EFG
France: Posaconazole Altan 300 mg solution à diluer pour perfusion
Italy: Posaconazolo Altan
Germany: Posaconazol Altan 300 mg Konzentrat zur Herstellung einer Infusionslösung
Poland: Pozakonazol Altan
United Kingdom (Northern Ireland): Posaconazole 300 mg concentrate for solution for infusion

Information intended exclusively for healthcare professionals

Instructions for administration of Pozakonazol Altan 300 mg concentrate for solution for infusion

• 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 to 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. Pozakonazol Altan concentrate for solution for infusion must not be administered as a rapid intravenous bolus injection.
• If a central venous catheter is unavailable, a single infusion with a volume allowing for a dilution of approximately 2 mg/mL may be administered via a peripheral venous catheter. When administering via a peripheral venous catheter, the infusion should last approximately 30 minutes. Note: In clinical trials, repeated peripheral infusions administered through the same vein led to infusion site reactions (see section 4.8).
• Pozakonazol Altan is intended for single use only.

The following medicinal products may be co-administered via the same intravenous line (or cannula) simultaneously with Pozakonazol Altan concentrate for solution for infusion:
Ciprofloxacin
Daptomycin
Gentamicin sulfate
Levofloxacin
Morphine sulfate
Norepinephrine bitartrate
Potassium chloride

All medicinal products not listed in the table above must not be administered simultaneously with Pozakonazol Altan through the same intravenous line (or cannula).
Pozakonazol Altan concentrate for solution for infusion should be visually inspected for particulate matter prior to administration. The solution of Pozakonazol Altan may be colorless or pale yellow. Variations in color within this range do not affect the quality of the product.
Any unused portions or waste material of the medicinal product should be disposed of in accordance with local regulations.

Pozakonazol Altan 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 and 0.45% sodium chloride solution
5% glucose and 0.9% sodium chloride solution
5% glucose and 20 mEq KCl