Voriconazol Adamed

Package Leaflet: Information for the User

Voriconazole Adamed, 200 mg, Powder for Solution for Infusion

Voriconazolum

Read the Package Leaflet Carefully Before Using the Medication, as it Contains Important Information for the Patient.

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

Table of Contents of the Package Leaflet:

What is Voriconazole Adamed and what is it used for
Important information before using Voriconazole Adamed
How to use Voriconazole Adamed
Possible side effects
How to store Voriconazole Adamed
Contents of the pack and other information

What is Voriconazole Adamed and what is it used for

Voriconazole Adamed contains the active substance voriconazole. Voriconazole Adamed is an antifungal medication. It works by killing fungi that cause infections or by stopping their growth.
The medication is used to treat patients (adults and children over 2 years of age) with:

• invasive aspergillosis (a type of fungal infection caused by fungi of the genus Aspergillus),
• candidemia (another type of fungal infection caused by fungi of the genus Candida) in patients without accompanying neutropenia (patients without abnormally decreased white blood cell count),
• severe, invasive fungal infections caused by fungi of the genus Candida that are resistant to fluconazole (another antifungal medication),
• severe fungal infections caused by fungi of the genus Scedosporium and Fusarium (two different types of fungi).

Voriconazole Adamed is intended for patients with progressive, life-threatening fungal infections.
The medication is intended to prevent fungal infections in patients at high risk after bone marrow transplantation.
This medication should only be used under the supervision of a doctor.

Important Information Before Using Voriconazole Adamed

When Not to Use Voriconazole Adamed

• if the patient is allergic to the active substance voriconazole or any of the other ingredients of this medication (listed in section 6).

It is very important to inform your doctor or pharmacist about all medications you are currently taking or have recently taken, including those that are available without a prescription or herbal remedies.
Do not take Voriconazole Adamed at the same time as:

• Terfenadine (used to treat allergies),
• Astemizole (used to treat allergies),
• Cisapride (used to treat stomach disorders),
• Pimozide (used to treat mental illnesses),
• Quinidine (used to treat heart rhythm disorders),
• Ivabradine (used to treat symptoms of chronic heart failure),
• Rifampicin (used to treat tuberculosis),
• Efavirenz (used to treat HIV infection) at doses of 400 mg or higher once a day,
• Carbamazepine (used to treat epilepsy),
• Phenobarbital (used to treat insomnia and epilepsy),
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine used to treat migraines),
• Sirolimus (used after organ transplantation),
• Ritonavir (used to treat HIV infection) at doses of 400 mg or higher twice a day,
• St. John's Wort (herbal preparation),
• Naloxegol [used to treat constipation caused by opioid painkillers (e.g., morphine, oxycodone, fentanyl, tramadol, codeine)],
• Tolvaptan [used to treat hyponatremia (low sodium levels in the blood) or to slow the worsening of kidney function in patients with polycystic kidney disease],
• Luraxadone (used to treat depression),
• Venetoclax (used to treat patients with chronic lymphocytic leukemia (CLL)).

Warnings and Precautions

Before starting treatment with Voriconazole Adamed, discuss with your doctor, pharmacist, or nurse if:

Avoid exposure to sunlight during treatment. It is essential to wear protective clothing and use sunscreens with a high sun protection factor (SPF), as skin sensitivity to sunlight (UV) may occur. These precautions also apply to children.
During treatment with Voriconazole Adamed:
inform your doctor immediately if you experience:
sunburn
severe skin rash or blisters
bone pain.
If skin disorders occur, your doctor may refer you to a dermatologist, who may decide on the need for regular follow-up visits after consultation. There is a small risk that long-term use of Voriconazole Adamed may cause skin cancer.
If you experience symptoms of "adrenal insufficiency"; a condition in which the adrenal glands do not produce enough of certain steroid hormones, such as cortisol; which can lead to symptoms such as: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain), inform your doctor.
If you experience symptoms of "Cushing's syndrome", a condition in which the body produces too much of the hormone cortisol, which can lead to symptoms such as: weight gain, appearance of a hump of fat between the shoulder blades, rounding of the face, darkening of the skin on the abdomen, thighs, chest, and arms, thinning of the skin, increased tendency to bruise, increased blood sugar levels, excessive hair growth, excessive sweating, inform your doctor.
Your doctor should regularly monitor your liver and kidney function with blood tests.

Children and Adolescents

Voriconazole Adamed should not be used in children under 2 years of age.

Voriconazole Adamed and Other Medications

Tell your doctor or pharmacist about all medications you are currently taking or plan to take, including those available without a prescription.
Some medications taken at the same time as Voriconazole Adamed may change its effect, and Voriconazole Adamed may affect the action of other medications.
Inform your doctor about taking the following medication, as it is recommended to avoid its concurrent use with Voriconazole Adamed:

• Ritonavir(used to treat HIV infection) at a dose of 100 mg twice a day.
• Glasdegib(used to treat cancer) - if it is necessary to use both medications, your doctor will order frequent monitoring of heart rhythm.

Inform your doctor about taking any of the following medications, as it is recommended to avoid their concurrent use with Voriconazole Adamed (if necessary, the dose of voriconazole may need to be changed):

• Rifabutin(used to treat tuberculosis). If you are being treated with rifabutin, you should have your blood count monitored and watch for signs of rifabutin side effects.
• Phenytoin(used to treat epilepsy). If you are being treated with phenytoin while taking Voriconazole Adamed, your doctor should monitor its blood levels and consider changing the dosage.

Inform your doctor about taking any of the following medications, as it may be necessary to change or monitor the dosage of these medications and/or Voriconazole Adamed to ensure they continue to work:

• Warfarin and other anticoagulant medications(e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting),
• Cyclosporine(used after organ transplantation),
• Tacrolimus(used after organ transplantation),
• Sulfonylurea derivatives(e.g., tolbutamide, glipizide, and gliburide) (used to treat diabetes),
• Statins(e.g., atorvastatin, simvastatin) (used to lower cholesterol levels),
• Benzodiazepines(e.g., midazolam, triazolam) (used to treat severe insomnia and stress),
• Omeprazole(used to treat stomach ulcers),
• Oral contraceptives(if Voriconazole Adamed is used concurrently with oral contraceptives, side effects such as nausea, menstrual disorders may occur),
• Vinca alkaloids(Vinca),e.g., vincristine and vinblastine (used to treat cancer),
• Tyrosine kinase inhibitors(e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used to treat cancer),
• Tretinoin(used to treat leukemia),
• HIV protease inhibitors(used to treat HIV infection),
• Non-nucleoside reverse transcriptase inhibitors(e.g., efavirenz, delavirdine, nevirapine) (used to treat HIV infection), (some doses of efavirenz should NOT be used concurrently with Voriconazole Adamed),
• Methadone(used to treat heroin addiction),
• Alfentanil, fentanyl, and other short-acting opioid painkillers,such as sufentanil (used during surgical procedures),
• Oxycodone and other long-acting opioid painkillers,such as hydrocodone (used to treat moderate to severe pain),
• Non-steroidal anti-inflammatory medications,e.g., ibuprofen, diclofenac (used to treat pain and inflammation),
• Fluconazole(used to treat fungal infections),
• Everolimus(used to treat advanced kidney cancer and in patients after organ transplantation),
• Letermovir(used to prevent cytomegalovirus (CMV) disease after bone marrow transplantation),
• Ivacaftor: used to treat cystic fibrosis.

Pregnancy and Breastfeeding

Do not use Voriconazole Adamed during pregnancyunless your doctor decides otherwise.
During treatment with Voriconazole Adamed, women of childbearing age must use effective contraception. If you become pregnant while taking Voriconazole Adamed, contact your doctor immediately.
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before using this medication.

Driving and Operating Machines

Voriconazole Adamed may cause vision disturbances and abnormal reactions to light.
In such cases, avoid driving vehicles and operating machines. Contact your doctor if you experience these disturbances.

Voriconazole Adamed Contains Hydroxypropylbetadex

The medication contains 2600 mg of hydroxypropylbetadex per 200 mg of voriconazole.
Do not use in children under 2 years of age without medical advice.
If you have kidney disease, consult your doctor before using this medication.

3. How to Use Voriconazole Adamed

Always use this medication exactly as your doctor has told you. If you are not sure, ask your doctor.
Your doctor will decide on the dose of the medication based on your body weight and the type of infection.
Your doctor may change the recommended dose depending on your clinical condition.
The usual recommended dosing in adults (including elderly patients) is presented in the table below:

Depending on the response to treatment, your doctor may increase the daily dose to 3 mg/kg body weight twice a day.
In cases of mild or moderate liver cirrhosis, your doctor may decide to reduce the dose of the medication.

Use in Children and Adolescents

The usual recommended dosing in children and adolescents is presented in the table below:

Intravenous

Children aged 2 to 12 years and adolescents aged 12 to 14 years with a body weight below 50 kg
Adolescents aged 12 to 14 years with a body weight above 50 kg or older and adolescents over 14 years of age
Dosing during the first 24 hours (loading dose)
9 mg/kg body weight every 12 hours during the first 24 hours
6 mg/kg body weight every 12 hours during the first 24 hours

Maintenance Dose After the First 24 Hours

8 mg/kg twice a day
4 mg/kg twice a day
Depending on the response to treatment, your doctor may increase or decrease the daily dose.
Voriconazole Adamed, powder for solution for infusion, will be dissolved and the resulting solution diluted to the appropriate concentration by a nurse or pharmacist (see information at the end of the package leaflet).
The medication will be administered by intravenous infusion at a maximum rate of 3 mg/kg body weight per hour over 1 to 3 hours.
If you are taking Voriconazole Adamed to prevent fungal infections and experience side effects related to treatment, your doctor may discontinue the administration of Voriconazole Adamed.

Missing a Dose of Voriconazole Adamed

Since the medication will be administered under close medical supervision, missing a dose is unlikely. However, if a dose is missed, inform your doctor or pharmacist.

Stopping Treatment with Voriconazole Adamed

Your doctor will decide how long you will be treated with Voriconazole Adamed; however, treatment with Voriconazole Adamed powder for solution for infusion should not exceed 6 months.
Patients with weakened immunity or severe infections may require long-term treatment to prevent disease recurrence. If clinical improvement occurs, the route of administration of Voriconazole Adamed may be changed from intravenous to oral.
If your doctor decides to stop the treatment, do not worry about the consequences of stopping it.
If you have any further questions about using this medication, ask your doctor, pharmacist, or nurse.

4. Possible Side Effects

Severe skin rash
Jaundice; changes in blood test results for liver function
Pancreatitis

Other Side Effects

Very common:may affect more than 1 in 10 people
Visual disturbances (changes in vision, including blurred vision, changes in color vision, abnormal light tolerance, loss of color vision, eye disorders, seeing flashes of light, night blindness, sensation of flickering, aura, decreased sharpness of vision, bright vision, loss of part of the usual field of vision, floaters) •
fever •rash •nausea, vomiting, diarrhea •headache •limb pain •abdominal pain •breathing difficulties •increased liver enzyme activity
Common:may affect up to 1 in 10 people
Sinusitis, gingivitis, chills, weakness •low count of certain types of blood cells, including severe cases, red and (or) white blood cells (sometimes associated with immunity) and (or) platelets, which help blood clot •low blood sugar, low potassium levels in the blood ,low sodium levels in the blood • anxiety, depression, confusion, agitation, insomnia, hallucinations • seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, drowsiness, dizziness • eye bleeding • heart rhythm disorders, including very fast or very slow heart rate, fainting • low blood pressure, vein inflammation (which may be associated with blood clot formation) • respiratory difficulties, chest pain, facial swelling (of the mouth, lips, and around the eyes), fluid retention in the lungs • constipation, indigestion, mouth inflammation • jaundice, liver inflammation and liver damage • skin rash that may lead to severe blistering and peeling •itching •hair loss •back pain •kidney failure, proteinuria, changes in kidney function tests
Uncommon:may affect up to 1 in 100 people
Flu-like symptoms, gastrointestinal irritation and inflammation, antibiotic-associated diarrhea, lymph node inflammation (sometimes painful), bone marrow failure, increased eosinophil count • adrenal gland disorders, hypothyroidism • brain disorders, Parkinson's disease-like symptoms, nerve damage causing numbness, pain, tingling, or burning sensations in the hands or feet, increased muscle tone, drowsiness, dizziness • balance or coordination disorders • brain swelling • double vision, severe eye disorders, including: eye pain and inflammation, abnormal eye movements, optic nerve damage leading to vision disturbances, swelling of the optic disc • decreased sensitivity to touch • taste disorders • hearing loss, ringing in the ears, dizziness • inflammation of certain internal organs - pancreas and duodenum, tongue swelling and inflammation • liver enlargement, liver failure, gallbladder disease, gallstones • joint inflammation, vein inflammation under the skin (which may be associated with blood clot formation) • kidney inflammation, proteinuria, kidney damage • very fast or very slow heart rate or skipped heartbeats, sometimes with abnormal electrical impulses • abnormal electrocardiogram (ECG) • increased cholesterol levels in the blood, increased urea levels in the blood • allergic skin reactions (sometimes severe), including a life-threatening skin condition characterized by painful blisters with skin and mucous membrane involvement, skin inflammation, hives, sunburn or severe skin reaction to light or sun exposure, skin redness and irritation, red or purple skin discoloration, which may be caused by a low platelet count, rash • infusion site reaction • allergic reaction or excessive immune response.
Rare:may affect up to 1 in 1000 people
Hyperthyroidism • worsening of brain function, which is a severe complication of liver disease

• loss of most of the optic nerve fibers, corneal clouding, involuntary eye movements • blistering rash due to sunlight sensitivity • disorders in which the immune system attacks part of the peripheral nervous system • heart rhythm disorders or conduction disorders (sometimes life-threatening) • life-threatening allergic reaction • blood clotting disorders • allergic skin reactions (sometimes severe), including sudden swelling (sudden swelling) of the skin, subcutaneous tissue, mucous membranes, and submucosal tissues, itching or painful patches of thickened, red skin with silvery scales, skin and mucous membrane irritation, life-threatening skin condition characterized by peeling of large areas of the outer layer of the skin from the underlying layers, small, dry, flaking skin patches, sometimes thickened with sharp protrusions or "horns"

Frequency not known(cannot be estimated from the available data)

• skin pigmentation and spots

Other important side effects, the frequency of which is not known, but which should be reported to your doctor immediately:

• -Skin cancer
• -Inflammation of the tissue surrounding the bone
• -Red, flaking patches or ring-shaped skin lesions, which may be a sign of an autoimmune disease called discoid lupus erythematosus

During infusion of Voriconazole Adamed, the following side effects have occurred uncommonly: flushing, fever, sweating, rapid heart rate, and shortness of breath. If these symptoms occur, your doctor may decide to discontinue the infusion.
Given the known effect of Voriconazole Adamed on the liver and kidneys, the function of these organs should be monitored with blood tests. You should also inform your doctor about abdominal pain or changes in stool consistency.
Sunburn or severe skin reactions to light or sun exposure occurred more frequently in children. If skin disorders occur, your doctor may refer you to a dermatologist, who may decide on the need for regular follow-up visits after consultation. Increased liver enzyme activity was also observed more frequently in children.

Reporting Side Effects

If you experience any side effects, including those not listed in this package leaflet, inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department for Monitoring of Adverse Reactions to Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, PL-02-222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl

5. How to Store Voriconazole Adamed

Keep this medication out of the sight and reach of children.
The reconstituted Voriconazole Adamed should be used immediately, but if necessary, it can be stored for up to 24 hours at a temperature of 2°C - 8°C (refrigerator).
The prepared solution should be diluted with a compatible infusion solution, always immediately before infusion (see information at the end of the package leaflet).
Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Contents of the Pack and Other Information

What Voriconazole Adamed Contains

• The active substance of the medication is voriconazole. Each vial contains 200 mg of voriconazole, which, after reconstitution according to the instructions by a hospital pharmacist or nurse (see information at the end of the package leaflet), yields 20 ml of a clear solution containing 10 mg/ml of voriconazole.
• The other ingredients are hydroxypropylbetadex and lactose monohydrate.

What Voriconazole Adamed Looks Like and Contents of the Pack

Voriconazole Adamed is available in single-dose glass vials, in the form of a powder for solution for infusion.

Marketing Authorization Holder

Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów

Manufacturer

Synthon BV
Microweg 22
6545 CM, Nijmegen
Netherlands
Synthon Hispania S.L.
C/Castelló 1
Polígono Las Salinas
08830 Sant Boi de Llobregat, Barcelona
Spain
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Date of last revision of the package leaflet:07.2022