Voriconazole Genoptim

Leaflet accompanying the packaging: patient information

Voriconazole Genoptim, 200 mg, powder for solution for infusion

Voriconazole

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• 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 only. 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 leaflet, please tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Voriconazole Genoptim and what is it used for
• 2. Important information before using Voriconazole Genoptim
• 3. How to use Voriconazole Genoptim
• 4. Possible side effects
• 5. How to store Voriconazole Genoptim
• 6. Contents of the packaging and other information

1. What is Voriconazole Genoptim and what is it used for

Voriconazole Genoptim contains the active substance voriconazole. Voriconazole Genoptim is an antifungal medicine. It works by killing fungi that cause infections or by stopping them from growing.

The medicine 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 who do not have a decreased number of white blood cells),
• severe, invasive fungal infections caused by fungi of the genus Candida that are resistant to fluconazole (another antifungal medicine),
• severe fungal infections caused by fungi of the genus Scedosporium and Fusarium (two different types of fungi).

Voriconazole Genoptim is intended for patients with progressive, life-threatening fungal infections.

The medicine is also intended to prevent fungal infections in patients at high risk after bone marrow transplantation.

This medicine should only be used under the supervision of a doctor.

2. Important information before using Voriconazole Genoptim

When not to use Voriconazole Genoptim:

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

Do not take Voriconazole Genoptim at the same time as:

• terfenadine (used to treat allergies),
• astemizole (used to treat allergies),
• cisapride (used to treat stomach disorders),
• pimozide (used in psychiatry),
• 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 and 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 in transplantation),
• ritonavir (used to treat HIV infection) at doses of 400 mg and higher twice a day,
• St. John's wort (herbal preparation),
• naloxegol (used to treat constipation caused by opioid painkillers),
• tolvaptan (used to treat hyponatremia 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 to take Voriconazole Genoptim, discuss with your doctor or nurse if:

• you have been diagnosed with hypersensitivity to other azoles.
• you have liver disease, including if it has occurred in the past. If you have liver disease, your doctor may prescribe a lower dose of Voriconazole Genoptim. Your doctor should also monitor your liver function during treatment with Voriconazole Genoptim by ordering blood tests.
• you have been diagnosed with cardiomyopathy, heart rhythm disorders, slow heart rate, or changes in the electrocardiogram (ECG) called QTc interval prolongation.

Avoid any exposure to sunlight during treatment. It is important to wear protective clothing and use sunscreens with a high sun protection factor (SPF) as sunburn may occur. This may be increased by other medicines that make the skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.

During treatment with Voriconazole Genoptim:

• Tell your doctor immediately if you experience
• sunburn
• severe skin rash or blisters
• bone pain

If the above skin disorders occur, your doctor may refer you to a dermatologist who, after consultation, may decide that regular check-ups are necessary.

There is a small risk that long-term use of Voriconazole Genoptim 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); symptoms include: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain), tell your doctor.

If you experience symptoms of Cushing's syndrome, a condition in which the body produces too much cortisol, which can lead to symptoms such as: weight gain, fatty hump between the shoulders, rounded face, darkening of the skin on the abdomen, thighs, breasts, and arms, thinning of the skin, easy bruising, high blood sugar, excessive hair growth, excessive sweating, tell your doctor.

Your doctor should regularly check your liver and kidney function with blood tests.

Children and adolescents

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

Voriconazole Genoptim and other medicines

Tell your doctor or pharmacist about all medicines you are taking now or have taken recently, as well as any medicines you plan to take, including those available without a prescription.

Some medicines taken at the same time as Voriconazole Genoptim may change its effect, as well as Voriconazole Genoptim may affect the effect of other medicines.

Tell your doctor if you are taking any of the following medicines, as it is recommended to avoid taking them at the same time as Voriconazole Genoptim:

• 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 medicines, your doctor will closely monitor your heart rhythm.

Tell your doctor if you are taking any of the following medicines, as it is recommended to avoid taking them at the same time as Voriconazole Genoptim (if it is necessary to use them, your doctor may adjust the dose of voriconazole):

• Rifabutin (used to treat tuberculosis). If you are being treated with rifabutin, your doctor should monitor your blood parameters and rifabutin side effects.
• Phenytoin (used to treat epilepsy). If you are being treated with phenytoin while taking Voriconazole Genoptim, your doctor should monitor its blood levels and consider adjusting the dosage.

Tell your doctor if you are taking any of the following medicines, as it may be necessary to adjust or monitor the dosage of these medicines and/or Voriconazole Genoptim to ensure they are still effective:

• warfarin and other anticoagulants (e.g. phenprocoumon, acenocoumarol) (used to reduce blood clotting),
• cyclosporine (used after organ transplantation),
• tacrolimus (used after organ transplantation),
• sulfonylureas (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 ulcers),
• oral contraceptives (if Voriconazole Genoptim is used at the same time as oral contraceptives, side effects such as nausea, menstrual disorders may occur),
• vinca alkaloids (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)
• protease inhibitors (e.g. indinavir and other 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 at the same time as Voriconazole Genoptim),
• methadone (used to treat heroin addiction),
• alfentanil, fentanyl, and other short-acting opioids, such as sufentanil (painkillers used during surgical procedures),
• oxycodone and other long-acting opioids, such as hydrocodone (used to treat moderate to severe pain),
• non-steroidal anti-inflammatory drugs (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 transplants),
• letermovir (used to prevent cytomegalovirus (CMV) disease after bone marrow transplantation),
• ivacaftor: used to treat cystic fibrosis,
• flucloxacillin (an antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Do not use Voriconazole Genoptim during pregnancy unless your doctor decides otherwise. During treatment with Voriconazole Genoptim, women of childbearing age must use effective contraception. If you become pregnant during treatment with Voriconazole Genoptim, contact your doctor immediately.

Driving and using machines

Voriconazole Genoptim may cause vision disturbances and abnormal reactions to light. In such cases, avoid driving and operating machinery.

Contact your doctor if you experience such disturbances.

Voriconazole Genoptim contains sodium

The medicine contains 88.74 mg of sodium (the main component of common salt) per vial.

This corresponds to 4.44% of the maximum recommended daily intake of sodium in the diet for adults.

Talk to your doctor or pharmacist if you need to take 5 or more vials per day for a long time, especially if you have been advised to follow a low-sodium diet.

Voriconazole Genoptim contains hydroxypropylbetadex

If you have kidney disease, talk to your doctor before taking the medicine.

3. How to use Voriconazole Genoptim

Always use this medicine exactly as your doctor has told you.

If you are not sure, ask your doctor.

Your doctor will decide on the dose of the medicine 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 dose in adults (including elderly patients) is presented in the table below:

Intravenous

Loading dose

(first 24 hours)

6 mg/kg body weight every 12 hours during the first 24 hours

Maintenance dose

(after the first 24 hours)

4 mg/kg body weight twice a day

Depending on the response to treatment, your doctor may reduce the dose to 3 mg/kg body weight twice a day.

In case of mild or moderate liver cirrhosis, your doctor may decide to reduce the dose of the medicine.

Use in children and adolescents

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

Intravenous

Adolescents aged 12 to 14 years with a body weight over 50 kg and adolescents over 14 years

Loading dose

(first 24 hours)

Children aged 2 to 12 years and adolescents aged 12 to 14 years with a body weight below 50 kg

6 mg/kg body weight every 12 hours during the first 24 hours

Maintenance dose

(after the first 24 hours)

9 mg/kg body weight every 12 hours during the first 24 hours

4 mg/kg body weight twice a day

Depending on the response to treatment, your doctor may increase or decrease the daily dose.

Voriconazole Genoptim, powder for solution for infusion, will be prepared by a nurse or pharmacist (see information at the end of the leaflet).

The medicine 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 Genoptim to prevent fungal infections, your doctor may stop the administration of Voriconazole Genoptim if side effects related to treatment occur.

Missed dose of Voriconazole Genoptim

Since the medicine will be administered under close medical supervision, missing a dose seems unlikely. However, if a dose is missed, always inform your doctor or nurse.

Stopping treatment with Voriconazole Genoptim

Your doctor will decide how long you will be given Voriconazole Genoptim; however, treatment with Voriconazole Genoptim, powder for solution for infusion, should not last longer than 6 months.

Patients with impaired immune systems or severe infections may require long-term treatment to prevent relapse of the disease.

If your doctor decides to stop therapy, do not worry about the consequences of stopping it.

If you have any further questions about using this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If side effects occur, they are usually mild and temporary.

However, some of them can be serious and may require medical attention.

Severe side effects

Stop using Voriconazole Genoptim immediately and contact your doctor if you experience:

Other side effects

Very common: may affect more than 1 in 10 people:

• Vision disturbances (changes in vision, including blurred vision, changes in color vision, abnormal light tolerance, loss of color vision, eye disorders, glare, night blindness, sensation of flickering image, seeing sparks, visual aura, decreased visual acuity, bright vision, loss of part of the normal field of vision, floaters)
• Fever
• Rash
• Nausea, vomiting, diarrhea
• Headache

• Peripheral edema
• Abdominal pain
• Breathing difficulties
• Increased liver enzyme activity

Common: may affect up to 1 in 10 people:

• Sinusitis, gingivitis, chills, weakness
• Low number of certain types of blood cells, including severe red blood cell (sometimes associated with immunity) and/or white blood cell (sometimes associated with fever) and/or platelet count
• Low blood sugar, low potassium, low sodium
• Anxiety, depression, confusion, agitation, insomnia, hallucinations
• Seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations, increased muscle tone, drowsiness, dizziness
• Retinal hemorrhage
• Heart rhythm disorders, including very rapid heart rate, very slow heart rate, fainting
• Low blood pressure, vein inflammation (which may be associated with blood clot formation)
• Breathing difficulties with rapid onset, chest pain, facial swelling (of the mouth, lips, and around the eyes), fluid accumulation in the lungs
• Constipation, indigestion, mouth inflammation
• Jaundice, liver inflammation, and liver damage
• Rashes that can lead to severe blistering and peeling of the skin, characterized by a flat, red area of skin covered with small merging bumps, redness of the skin
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in urine, 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
• Inflammation of the thin tissue lining the abdominal cavity and covering the abdominal organs
• Lymph node enlargement (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
• Balance or coordination disorders
• Brain swelling
• Double vision, severe eye disorders, including: eye pain and inflammation, abnormal eye movements, optic nerve damage causing 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 inflammation and swelling
• Liver enlargement, liver failure, gallbladder disease, gallstones

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

• Hyperthyroidism
• Worsening of brain function, which is a severe complication of liver disease
• Loss of most of the nerve fibers of the optic nerve, cataract, involuntary eye movement
• Blisters due to sun 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
• Skin allergic 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 silver scales, skin and mucous membrane irritation, life-threatening skin disease characterized by peeling off large patches of the outer layer of skin (epidermis) from the underlying layers of skin.

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

• Pigmentation and skin discoloration

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, peeling patches or ring-shaped skin lesions, which may be a sign of an autoimmune disease called discoid lupus erythematosus.

During infusion of Voriconazole Genoptim, infrequent side effects such as flushing, fever, sweating, rapid heart rate, and shortness of breath may occur. If these symptoms occur, your doctor may decide to stop the infusion.

Due to the known effect of Voriconazole Genoptim on the liver and kidneys, the function of these organs should be monitored with blood tests.

You should also inform your doctor if you experience abdominal pain or changes in stool consistency.

Cases of skin cancer have been reported in patients treated with Voriconazole Genoptim for a long time.

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, after consultation, may decide that regular check-ups are necessary. Increased liver enzyme activity was also observed more frequently in children.

If any of these side effects persist or bother you, tell your doctor.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides of the Office for Registration of Medicinal Products:

Jerozolimskie Avenue 181C

02-222 Warsaw

tel.: +48 22 49 21 301

fax: +48 22 49 21 309

website: https://smz.ezdrowie.gov.pl.

Side effects can also be reported to the marketing authorization holder.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Voriconazole Genoptim

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial after EXP.

The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Chemical and physical stability has been demonstrated during use for 72 hours at 25°C and at 2°C-8°C.

From a microbiological point of view, Voriconazole Genoptim once reconstituted should be used immediately.

If not used immediately, the storage time of the concentrate should not exceed 24 hours at 2°C-8°C, provided that the reconstitution was performed under controlled and validated aseptic conditions.

Reconstituted Voriconazole Genoptim should be diluted in a compatible infusion solution immediately before infusion.

Medicines should not be disposed of via wastewater 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 Voriconazole Genoptim contains

• The active substance of the medicine is voriconazole. Each vial contains 200 mg of voriconazole. After reconstitution, each ml of solution contains 10 mg of voriconazole.
• The other ingredients of the medicine are hydroxypropylbetadex, sodium chloride, concentrated hydrochloric acid (for pH adjustment).

What Voriconazole Genoptim looks like and contents of the pack

Each pack contains one vial. Voriconazole Genoptim is a white or off-white lyophilized powder for solution for infusion in a 25 ml vial of colorless glass type I with a gray rubber stopper and an aluminum seal with a plastic, red flip-off cap (flip-off closure) in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder

Synoptis Pharma Sp. z o.o.

Krakowiaków 65

02-255 Warsaw

Manufacturer

Pharmathen S.A.

6, Dervenakion str.

153 51, Pallini, Attiki

Greece

Anfarm Hellas S.A.

320 09, Schimatari Viotias

Greece

Pharmathen International S.A.

Sapes Industrial Park Block 5

69300 Rodopi

Greece

This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Netherlands

Voriconazole Pharmathen 200mg powder for solution for infusion

Spain

Voriconazol Aurovitas Spain 200 mg powder for solution for perfusion

France

VORICONAZOLE STRAGEN 200 mg powder for solution for perfusion

United Kingdom (Northern Ireland)

Voriconazole 200 mg powder for solution for infusion PL 35533/0036

Germany

Voriconazol PUREN 200 mg powder for solution for infusion ENR 2191998

Date of last revision of the leaflet:July 2024

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Information intended for healthcare professionals only:

Information on reconstitution (preparation of concentrate) and dilution:

• Voriconazole Genoptim, powder for solution for infusion, should be reconstituted in 19 ml of water for injection or 19 ml of 9 mg/ml (0.9%) sodium chloride injection to obtain 20 ml of a clear concentrate containing 10 mg/ml of voriconazole.
• The vial of Voriconazole Genoptim should be discarded if, during the introduction of the solvent, it is not drawn into the vial by the existing vacuum.
• To ensure accurate measurement of the volume (19 ml) of water for injection or 9 mg/ml (0.9%) sodium chloride injection, it is recommended to use standard 20 ml (non-automated) syringes.
• In order to obtain a solution for infusion containing 0.5 mg/ml to 5 mg/ml of voriconazole, the required volume of the prepared concentrate should be added to the recommended compatible infusion solution (see below).
• This solution is for single use only. Unused solution should be discarded. Do not use cloudy solutions or solutions containing particles.
• The solution is not intended for rapid intravenous injection (bolus).
• Information on storage is included in section 5 "How to store Voriconazole Genoptim".

Required volumes of Voriconazole Genoptim concentrate 10 mg/ml

Body weight (kg)

Volume of Voriconazole Genoptim concentrate (10 mg/ml) required for a dose of 3 mg/kg 4 mg/kg 6 mg/kg 8 mg/kg 9 mg/kg body weight (number of vials)

body weight (number of vials)

body weight (number of vials)

body weight (number of vials)

body weight (number of vials)

10

• 4.0 ml (1)
• 8.0 ml (1) 9.0 ml (1) 15
• 6.0 ml (1)
• 12.0 ml (1) 13.5 ml (1) 20
• 8.0 ml (1)
• 16.0 ml (1) 18.0 ml (1) 25
• 10.0 ml (1)
• 20.0 ml (1) 22.5 ml (2) 30 9.0 ml (1) 12.0 ml (1) 18.0 ml (1) 24.0 ml (2) 27.0 ml (2) 35 10.5 ml (1) 14.0 ml (1) 21.0 ml (2) 28.0 ml (2) 31.5 ml (2) 40 12.0 ml (1) 16.0 ml (1) 24.0 ml (2) 32.0 ml (2) 36.0 ml (2) 45 13.5 ml (1) 18.0 ml (1) 27.0 ml (2) 36.0 ml (2) 40.5 ml (3) 50 15.0 ml (1) 20.0 ml (1) 30.0 ml (2) 40.0 ml (2) 45.0 ml (3) 55 16.5 ml (1) 22.0 ml (2) 33.0 ml (2) 44.0 ml (3) 49.5 ml (3) 60 18.0 ml (1) 24.0 ml (2) 36.0 ml (2) 48.0 ml (3) 54.0 ml (3) 65 19.5 ml (1) 26.0 ml (2) 39.0 ml (2) 52.0 ml (3) 58.5 ml (3) 70 21.0 ml (2) 28.0 ml (2) 42.0 ml (3)
• 75 22.5 ml (2) 30.0 ml (2) 45.0 ml (3)
• 80 24.0 ml (2) 32.0 ml (2) 48.0 ml (3)
• 85 25.5 ml (2) 34.0 ml (2) 51.0 ml (3)
• 90 27.0 ml (2) 36.0 ml (2) 54.0 ml (3)
• 95 28.5 ml (2) 38.0 ml (2) 57.0 ml (3)
• 100 30.0 ml (2) 40.0 ml (2) 60.0 ml (3)

Voriconazole Genoptim is a non-sterile, sterile lyophilisate intended for single use.

Therefore, from a microbiological point of view, the prepared concentrate should be used immediately.

If the concentrate is not used immediately, the user is responsible for the storage time and conditions before use.

The storage time of the concentrate should not exceed 24 hours at 2°C-8°C, provided that the reconstitution was performed under controlled and validated aseptic conditions.

number of vials)

number of vials)

number of vials)

number of vials)

Compatible infusion solutions:

The concentrate can be diluted in:

9 mg/ml (0.9%) sodium chloride injection

sodium lactate injection

5% glucose and 5% glucose with 0.45% sodium chloride injection

5% glucose with 0.45% sodium chloride injection

5% glucose injection

5% glucose in 20 mEq potassium chloride injection

0.45% sodium chloride injection

5% glucose and 9 mg/ml (0.9%) sodium chloride injection

Compatibility of Voriconazole Genoptim with other solutions than those listed above (or listed in the "Incompatibilities" section below) has not been established.

Incompatibilities:

Voriconazole Genoptim should not be infused at the same time as other medicines through the same cannula or intravenous access, including parenteral nutrition (e.g. Aminofusin 10% Plus).

Intravenous infusions for parenteral nutrition can be administered at the same time as voriconazole, but not through the same intravenous access or cannula.

4.2% sodium bicarbonate injection should not be used to dilute Voriconazole Genoptim.