Voriconazole Sandoz

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

Voriconazole Sandoz contains the active substance voriconazole. Voriconazole Sandoz is an antifungal medicine that kills fungi causing infections or stops 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 neutropenia (patients without an abnormally low number of white blood cells);
severe invasive fungal infections caused by fungi of the genus Candida, resistant to fluconazole (another antifungal medicine);
severe fungal infections caused by fungi of the genus Scedosporiumor Fusarium(two different types of fungi).
Voriconazole Sandoz is intended for patients with progressive, life-threatening fungal infections.
The medicine is intended to prevent fungal infections in high-risk patients after bone marrow transplantation.
This medicine should only be used under the supervision of a doctor.

2. Important information before taking Voriconazole Sandoz

When not to take Voriconazole Sandoz:

• if the patient is allergic to voriconazole or to betacyclodextrin sulfobutyl ether sodium (listed in section 6.1).

It is very important to inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as medicines the patient plans to take, even those that are available without a prescription or are herbal medicines.
The following medicines must not be taken during treatment with Voriconazole Sandoz:
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) in doses of 400 mg or higher, taken once a day;
carbamazepine (used to treat epilepsy);
phenobarbital (used to treat severe insomnia and epilepsy);
ergot alkaloids (e.g., ergotamine, dihydroergotamine, used to treat migraines);
sirolimus (used in patients after organ transplantation);
ritonavir (used to treat HIV infection) in doses of 400 mg or higher, taken twice a day;
St. John's Wort (herbal medicine);
naloxegol [used to treat constipation caused by painkillers from the opioid group (e.g., morphine, oxycodone, fentanyl, tramadol, codeine)];
tolvaptan [used to treat hyponatremia (a condition of low sodium levels in the blood) or to slow the deterioration of kidney function in patients with polycystic kidney disease];
luraxadone (used to treat depression);
venetoclax [used to treat patients with chronic lymphocytic leukemia (CLL, chronic lymphocytic leukemia)].

Warnings and precautions

Before taking Voriconazole Sandoz, the patient should discuss with their doctor, pharmacist, or nurse if:
they have had an allergic reaction to other azoles in the past;
they have or have had liver disease. The doctor may prescribe a lower dose of Voriconazole Sandoz and recommend blood tests to monitor liver function during treatment.
they have been diagnosed with cardiomyopathy, irregular heart rhythm, slow heart rate, or changes in the electrocardiogram (ECG) called "prolonged QT interval".
During treatment, the patient should avoid any exposure to sunlight. It is essential to wear protective clothing and use sunscreens with a high protection factor (SPF), as skin sensitivity to sunlight (UV) may occur. This may be exacerbated by other medicines that make the skin sensitive to sunlight, such as methotrexate. These precautions also apply to children.
During treatment with Voriconazole Sandoz:
the patient should immediately inform their doctor if they experience:
sunburn
severe rash or blisters on the skin
bone pain
The doctor may refer the patient to a dermatologist if they experience the above skin changes. Regular dermatological consultations may be necessary. Long-term use of Voriconazole Sandoz may be associated with a small risk of developing skin cancer.
The patient should tell their doctor if they experience symptoms of "adrenal insufficiency", a condition in which the adrenal glands do not produce enough steroid hormones, such as cortisol. These symptoms include: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain.
If the patient experiences 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 fatty hump between the shoulder blades, rounding of the face, darkening of the skin on the abdomen, thighs, chest, and arms, thinning of the skin, increased bruising, increased blood sugar levels, excessive hair growth, excessive sweating, they should inform their doctor.
The doctor will monitor the patient's liver and kidney function with blood tests.

Children and adolescents

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

Voriconazole Sandoz and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as medicines they plan to take, including those available without a prescription.
Some medicines taken at the same time as Voriconazole Sandoz may change its effect, and Voriconazole Sandoz may affect the action of other medicines.
If the patient is taking any of the following medicines, they should tell their doctor, as it may be necessary to avoid taking them at the same time as Voriconazole Sandoz or to modify the dose of voriconazole:
ritonavir (used to treat HIV infection) at a dose of 100 mg taken twice a day;
glasdegib (used to treat cancer) — if it is necessary to take both medicines, the doctor will order frequent heart rhythm monitoring.
If the patient is taking any of the following medicines, they should tell their doctor, as it may be necessary to avoid taking them at the same time as Voriconazole Sandoz or to modify the dose of voriconazole:
rifabutin (used to treat tuberculosis). If the patient is being treated with rifabutin, it will be necessary to monitor their blood count and watch for side effects of rifabutin.
phenytoin (used to treat epilepsy). If the patient is being treated with phenytoin, during treatment with Voriconazole Sandoz, it will be necessary to monitor its blood levels and the doctor may modify the dosing.
If the patient is taking any of the following medicines, they should tell their doctor, as it may be necessary to modify or monitor the dosing to ensure that the mentioned medicines and/or Voriconazole Sandoz still have the expected effect:
warfarin and other anticoagulant medicines (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 reduce cholesterol levels);
benzodiazepines, e.g., midazolam, triazolam (used to treat severe insomnia and stress);
omeprazole (used to treat stomach ulcers);
oral contraceptives (if Voriconazole Sandoz is taken 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),
HIV 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); certain doses of efavirenz should not be taken at the same time as Voriconazole Sandoz;
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 or severe pain);
non-steroidal anti-inflammatory medicines, 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,
flucloxacillin (an antibiotic used to treat bacterial infections)

Pregnancy and breastfeeding

Voriconazole Sandoz should not be taken during pregnancy, unless the doctor decides otherwise.
During treatment with Voriconazole Sandoz, women of childbearing age must use effective contraception. If the patient becomes pregnant while taking Voriconazole Sandoz, they should contact their doctor immediately.
If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.

Driving and using machines

Voriconazole Sandoz may cause vision disturbances and discomforting sensitivity to light. In this case, the patient should avoid driving and operating machines.
If such disturbances occur, the patient should contact their doctor.

Voriconazole Sandoz contains sodium and betacyclodextrin sulfobutyl ether sodium

This medicine contains up to 228.7 mg of sodium (the main component of common salt) per vial. This corresponds to 11.4% of the maximum recommended daily intake of sodium in the diet for adults.
This medicine contains 3.4 g of betacyclodextrin sulfobutyl ether sodium per vial. If the patient has kidney disease, they should consult their doctor before taking this medicine.

3. How to take Voriconazole Sandoz

This medicine should always be taken according to the doctor's instructions. In case of doubts, the patient should consult their doctor.
The doctor determines the dose of the medicine based on the patient's body weight and the type of infection. The doctor may also change the dose depending on the patient's health condition.
The recommended dosing for adults (including elderly patients) is as follows:

Intravenously

Dosing during the first 24 hours

(loading dose)
6 mg/kg body weight every 12 hours

Dosing after the first 24 hours

(maintenance dose)
4 mg/kg body weight twice a day
Depending on the patient's response to treatment, the doctor may reduce the dose to 3 mg/kg body weight twice a day.
If the patient has mild or moderate liver cirrhosis, the doctor may decide to reduce the dose of the medicine.

Use in children and adolescents

The recommended dosing for children and adolescents is as follows:

Intravenously

Children from 2 to <12 years and adolescents
Adolescents from 12 to 14 years with a body weight
of 12 to 14 years with a body weight of 50 kg or more and
adolescents over 14 years

Dosing during the first 24 hours

(loading dose)
less than 50 kg
9 mg/kg body weight every 12 hours
6 mg/kg body weight every 12 hours

Dosing after the first 24 hours

(maintenance dose)
8 mg/kg body weight twice a day
4 mg/kg body weight twice a day
Depending on the patient's response to treatment, the doctor may increase or decrease the daily dose.
Voriconazole Sandoz in the form of powder for solution for infusion will be dissolved and then diluted to the appropriate concentration by hospital staff (further information can be found at the end of this leaflet).
The medicine is administered over 1 to 3 hours in intravenous infusion at a maximum rate of 3 mg/kg body weight/hour.
If the patient receiving Voriconazole Sandoz for the prevention of fungal infections experiences treatment-related side effects, the treating doctor may discontinue the administration of Voriconazole Sandoz.

Missing a dose of Voriconazole Sandoz

The medicine is administered under close medical supervision, so missing a dose is unlikely. However, if the patient has doubts about whether they received the medicine, they should consult their doctor or pharmacist.

Discontinuing Voriconazole Sandoz

The duration of treatment is determined by the doctor, but Voriconazole Sandoz in the form of intravenous infusion should not be used for more than 6 months.
In patients with weakened immunity or severe infections, long-term treatment may be necessary to prevent the recurrence of the disease. After the patient's condition improves, the doctor may switch from intravenous to oral treatment (tablets).
If the doctor decides to discontinue Voriconazole Sandoz, the patient should not be concerned about the consequences of this discontinuation.
If the patient has any further doubts about the use of this medicine, they should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Voriconazole Sandoz can cause side effects, although not everybody gets them.
If a side effect occurs, it is usually mild and temporary. However, some of them can be serious and may require medical attention.
Severe side effects should be reported to the doctor immediately and the use of Voriconazole Sandoz should be discontinued:

Sandoz:

rash
jaundice; changes in blood test results evaluating liver function
pancreatitis

Other side effects

Very common(may occur in more than 1 in 10 people):
vision disturbances (changes in vision, including blurred vision, changes in color vision, abnormal light tolerance, lack of color vision, eye disorders, seeing flashes of light, night blindness, feeling of image vibration, seeing sparks, visual aura, decreased visual acuity, bright vision, loss of part of the usual field of vision, floaters in front of the eyes)
fever
rash
nausea, vomiting, diarrhea
headache
swelling of limbs
abdominal pain
breathing difficulties
increased liver enzyme activity
Common(may occur in less than 1 in 10 people):
sinusitis, gingivitis, chills, weakness
low (sometimes significantly low) number of certain types of red blood cells (sometimes associated with immunity) and/or white blood cells (sometimes with fever), low number of platelets, which help blood to clot
low blood sugar levels, low potassium levels, low sodium levels
anxiety, depression, feeling of confusion, agitation, insomnia, hallucinations
seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tension, drowsiness, dizziness
bleeding in the eye
heart rhythm disturbances, including very fast heart rate, very slow heart rate, fainting
low blood pressure, vein inflammation (which may be associated with the formation of blood clots)
breathing difficulties with a rapid onset, chest pain, swelling of the face (mouth, lips, and eyes), fluid accumulation in the lungs
constipation, indigestion, mouth inflammation
jaundice, liver inflammation, and liver damage
skin rash, which can progress to a severe form with blisters and peeling, characterized by a flat, red area on the skin covered with small, merging bumps, redness of the skin
itching
hair loss
back pain
kidney failure, presence of blood in the urine, changes in blood test results evaluating kidney function
sunburn or severe skin reaction after exposure to light or sun
skin cancer
Uncommon(may occur in less than 1 in 100 people):
flu-like symptoms, irritation, and inflammation of the mucous membrane of the digestive tract, antibiotic-associated diarrhea, inflammation of the lymphatic vessels
inflammation of the thin tissue lining the inner wall of the abdominal cavity and surrounding the abdominal organs
enlarged lymph nodes (sometimes painful), bone marrow failure, increased number of eosinophils
adrenal gland disorders, hypothyroidism
abnormal brain function, symptoms similar to Parkinson's disease, nerve damage causing numbness, pain, tingling, or burning sensations in the hands or feet, balance, or coordination disturbances
brain swelling
double vision, severe eye disorders, including pain and inflammation of the eyeballs and eyelids, abnormal eye movements, damage to the optic nerve resulting in vision disturbances, swelling of the optic disc
decreased sensitivity to touch
taste disturbances
hearing disturbances, ringing in the ears, dizziness
inflammation of certain internal organs — pancreas and duodenum, swelling, and inflammation of the tongue
enlarged liver, liver failure, gallbladder disease, gallstones
joint inflammation, vein inflammation (which may cause blood clots to form)
kidney inflammation, presence of protein in the urine, kidney damage
very fast heart rate or skipped heartbeats, sometimes with abnormal electrical impulses
abnormal electrocardiogram (ECG) reading
increased cholesterol levels, increased urea levels in the blood
severe skin allergic reactions (sometimes life-threatening), including a condition characterized by painful blisters and peeling of the skin, redness of the skin
reaction at the injection site
allergic reaction or excessive immune response
inflammation of the tissue surrounding the bone
Rare(may occur in less than 1 in 1000 people):
hyperthyroidism
severe brain function impairment, which is a serious complication of liver disease
loss of most of the nerve fibers in the optic nerve, cataract, involuntary eye movement
blistering rash due to sun sensitivity
disorders in which the immune system attacks part of the peripheral nervous system
heart rhythm disturbances or conduction disorders (sometimes life-threatening)
life-threatening allergic reaction
blood clotting disorders
severe skin allergic reactions (sometimes life-threatening), including a condition characterized by painful blisters and peeling of the skin, itching or painful patches of thickened, red skin with silver scales, irritation of the skin and mucous membranes, a life-threatening skin disease characterized by the separation of large flakes of the outer layer of the skin from the underlying layers
appearance of small, dry, flaky skin patches, sometimes thickened, with sharp protrusions or "horns"
Frequency not known(cannot be estimated from the available data)
pigmentation and skin spots
Other important side effects, the frequency of which is not known, but which should be reported to the doctor immediately:
red, flaky, or ring-shaped skin changes, which may be a sign of an autoimmune disease called cutaneous lupus erythematosus
Infusion-related reactions to Voriconazole Sandoz (flushes, fever, increased sweating, rapid heart rate, and shortness of breath) occur uncommonly. The doctor may then discontinue the administration of the medicine.
Due to the known effect of Voriconazole Sandoz on the liver and kidneys, the doctor will monitor the function of these organs by ordering blood tests. If the patient experiences abdominal pain or changes in stool consistency, they should consult their doctor.
There have been reports of skin cancer development in patients treated with voriconazole for a long time.
Sunburn or severe skin reactions after exposure to light or sun occurred more frequently in children. If the patient experiences skin disturbances, the doctor may refer them to a dermatologist, who may decide on the need for regular check-ups after consulting. Children also experienced more frequent increases in liver enzyme activity.
If any of these side effects persist or are troublesome, the patient should inform their doctor.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
phone: +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.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Voriconazole Sandoz

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after "EXP". The expiry date refers to the last day of the month.
Store at a temperature below 30°C.
Reconstituted solution
It has been demonstrated that the reconstituted solution retains its chemical and physical stability for 24 hours at a temperature between 2°C and 8°C.
Infusion solution after dilution
It has been demonstrated that the diluted solution retains its chemical and physical stability for 3 hours at a temperature between 20°C and 30°C.
For microbiological reasons, the prepared solution should be used immediately. Otherwise, the time and conditions of its storage before use are the responsibility of the user. The storage time should not exceed 24 hours at a temperature between 2°C and 8°C (refrigerator), unless the solution was prepared in controlled and validated aseptic conditions.
(Further information can be found at the end of this leaflet.)
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Voriconazole Sandoz contains

• The active substance is voriconazole. Each vial contains 200 mg of powder for solution for infusion, which corresponds to a concentration of 10 mg/ml after reconstitution according to the instructions by the hospital pharmacist or nurse (see information at the end of this leaflet).
• The other ingredient is betacyclodextrin sulfobutyl ether sodium.

What Voriconazole Sandoz looks like and contents of the pack

Single-dose, colorless vials with a capacity of 25 ml made of type I glass, closed with a rubber stopper and a flip-off cap with a plastic disc, and placed in a cardboard box.
Pack sizes: 1 or 10 vials of powder for solution for infusion.

Marketing authorization holder and manufacturer

Marketing authorization holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria
Manufacturer
Lek Pharmaceuticals d.d.
Verovškova 57
1526 Ljubljana, Slovenia
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany

To obtain more detailed information on the medicine and its names in other EU member states, please contact:

Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
phone: 22 209 70 00
Date of last revision of the leaflet:07/2024
Sandoz logo
Information intended for healthcare professionals only:

Reconstitution and dilution of the solution

 The powder for solution for infusion Voriconazole Sandoz should be dissolved in 19 ml of water for injection or 19 ml of 0.9% (9 mg/ml) sodium chloride solution for infusion to obtain 20 ml of a clear concentrate containing voriconazole at a concentration of 10 mg/ml.
 If the vacuum in the vial did not cause the diluent to be introduced into the vial, such a vial should be discarded.
 To measure the exact volume (19.0 ml) of water for injection or 0.9% sodium chloride solution for infusion, it is recommended to use a standard (non-automatic) 20 ml syringe.
 To obtain the final solution of Voriconazole Sandoz, containing voriconazole at a concentration of 0.5-5 mg/ml, the required volume of the concentrate should be added to one of the following recommended compatible infusion solutions.
 The medicinal product is intended for single use, and any unused solution should be discarded. Only clear solutions without solid particles should be used.
 The medicine is not intended for rapid injection (bolus).
 Information on storage, see section 5 "How to store Voriconazole Sandoz".
Required volumes of Voriconazole Sandoz concentrate 10 mg/ml

Body weight Dose (number of vials) dose:

3 mg/kg body weight (number of vials) dose:

4 mg/kg body weight (number of vials) dose:

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 Sandoz is a preservative-free, sterile lyophilisate, intended for single-dose administration. Therefore, for microbiological reasons, the prepared solution should be used immediately. Otherwise, the time and conditions of its storage before use are the responsibility of the user. The storage time should not exceed 24 hours at a temperature between 2°C and 8°C (refrigerator), unless the solution was prepared in controlled and validated aseptic conditions.
(Further information can be found at the end of this leaflet.)
Required volumes of Voriconazole Sandoz concentrate 10 mg/ml for:

6 mg/kg body weight (number of vials) dose:

8 mg/kg body weight (number of vials)

i potwierdzonych warunkach aseptycznych.

Compatible infusion solutions

The reconstituted solution can be diluted using:
9 mg/ml (0.9%) sodium chloride solution for infusion
lactated Ringer's solution for infusion
5% glucose solution and lactated Ringer's solution for infusion
5% glucose solution and 0.45% sodium chloride solution for infusion
5% glucose solution for infusion
5% glucose solution in 20 mEq potassium chloride solution for infusion
0.45% sodium chloride solution for infusion
5% glucose solution and 0.9% sodium chloride solution for infusion
The compatibility of voriconazole with diluents other than those listed above (or below in the "Incompatibilities" section) is not known.
Incompatibilities
The solution of Voriconazole Sandoz should not be administered together with other medicines in the same infusion line or intravenous access. This also applies to parenteral nutrition.
Blood products should not be administered simultaneously with Voriconazole Sandoz.
Parenteral nutrition can be administered simultaneously with Voriconazole Sandoz, but it should be administered through a separate intravenous access or line.