Voriconazole sandoz: detailed information

Package leaflet: Information for the patient

Voriconazole Sandoz, 200 mg, film-coated tablets
Voriconazolum
Please read all of this leaflet carefully before taking 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 only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

What Voriconazole Sandoz is and what it is used for
What you need to know before taking Voriconazole Sandoz
How to take Voriconazole Sandoz
Possible side effects
How to store Voriconazole Sandoz
Contents of the pack and other information

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

Voriconazole Sandoz contains the active substance voriconazole. Voriconazole Sandoz is an antifungal medicine that kills or inhibits the growth of fungi causing infections.
This medicine is used to treat patients (adults and children aged 2 years and older) with:
invasive aspergillosis (a type of fungal infection caused by fungi of the genus Aspergillus);
candidaemia (another type of fungal infection caused by fungi of the genus Candida) in patients without neutropenia (patients who do not have abnormally low levels of white blood cells);
serious invasive fungal infections caused by Candida species that are resistant to fluconazole (another antifungal medicine);
serious fungal infections caused by Scedosporium or Fusarium species (two different types of fungi).
Voriconazole Sandoz is intended for patients with progressive, potentially life-threatening fungal infections.
It is also used 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 Sandoz

When not to use Voriconazole Sandoz

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

The doctor or pharmacist should be informed about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to use, including those available without a prescription or herbal medicines.
Do not use the following medicines during treatment with Voriconazole Sandoz:
terfenadine (used to treat allergies);
astemizole (used to treat allergies);
cisapride (used for stomach disorders);
pimozide (used to treat psychiatric disorders);
quinidine (used for 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 taken once daily;
carbamazepine (used to treat epilepsy);
phenobarbital (used to treat severe insomnia and epilepsy);
ergot alkaloids (e.g. ergotamine, dihydroergotamine, used to treat migraine);
sirolimus (used in organ transplant patients);
ritonavir (used to treat HIV infection) at doses of 400 mg or higher taken twice daily;
St John’s wort (herbal medicine);
naloxegol [used to treat constipation caused by opioid pain medicines (e.g. morphine, oxycodone, fentanyl, tramadol, codeine)];
tolvaptan [used to treat hyponatremia (low sodium levels in blood) or to slow the decline in kidney function in patients with polycystic kidney disease];
lurasidone (used to treat depression);
finerenone (used to treat chronic kidney disease);
eplerenone (used to treat heart and/or blood vessel diseases);
voclosporin (used to treat immune disorders);
venetoclax [used to treat patients with chronic lymphocytic leukaemia (CLL)].

Warnings and precautions
Before using Voriconazole Sandoz, discuss this with the doctor, pharmacist, or nurse if:
 the patient has previously experienced an allergic reaction to other azoles;
 the patient has or has ever had liver disease; the doctor may prescribe a lower dose of Voriconazole Sandoz and recommend blood tests to monitor liver function during treatment;
 the patient has been diagnosed with cardiomyopathy, irregular heartbeat, slow heart rate, or changes in the electrocardiogram (ECG) known as “prolonged QTc interval”.

During treatment, avoid any exposure to sunlight. It is important to wear protective clothing and use high sun protection factor (SPF) sunscreen, as skin photosensitivity reactions (UV sensitivity) may occur. This may be further intensified by other medicines that increase skin sensitivity to sunlight, such as methotrexate. These precautions also apply to children.

During treatment with Voriconazole Sandoz, inform the doctor immediately if the patient develops:
sunburn;
severe rash or blisters;
bone pain.

If the patient develops the skin disorders described above, the doctor may refer the patient to a dermatologist, who may decide after consultation that regular follow-up visits are necessary. There is a small risk that long-term use of voriconazole may lead to skin cancer.

Inform the doctor if the patient develops symptoms of “adrenal insufficiency”, in which the adrenal glands do not produce sufficient amounts of certain steroid hormones such as cortisol. Symptoms include: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain.

If the patient develops symptoms of “Cushing’s syndrome”, in which the body produces too much of the hormone cortisol, leading to symptoms such as weight gain, development of a fatty hump between the shoulders, rounded face, darkening of the skin on the abdomen, thighs, chest and arms, thinning of the skin, increased tendency to bruising, elevated blood sugar levels, excessive hair growth, and excessive sweating, inform the doctor.

The doctor will monitor the patient’s liver and kidney function through blood tests.

Children and adolescents
Voriconazole Sandoz must not be used in children under 2 years of age.

Voriconazole Sandoz and other medicines
Inform the doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to use, including those available without a prescription.

Some medicines taken together with Voriconazole Sandoz may alter its effects, and Voriconazole Sandoz may also affect the action of other medicines.

If the patient is taking any of the following medicines, inform the doctor, as their concomitant use with Voriconazole Sandoz should be avoided if possible:
 ritonavir (used to treat HIV infection) at a dose of 100 mg taken twice daily;
 glasdegib (used to treat cancers) — if co-administration is necessary, the doctor will arrange frequent monitoring of heart rhythm.

If the patient is taking any of the following medicines, inform the doctor, as their concomitant use with Voriconazole Sandoz should be avoided if possible, or dose adjustment of voriconazole may be required:
Rifabutin (used to treat tuberculosis). If the patient is being treated with rifabutin, monitoring of blood counts and observation for adverse effects of rifabutin will be necessary.
Phenytoin (used to treat epilepsy). If the patient is being treated with phenytoin, monitoring of its blood levels will be necessary during Voriconazole Sandoz treatment, and the doctor may adjust the dose.

If the patient is taking any of the following medicines, inform the doctor, as dose adjustment or monitoring may be required to ensure that these medicines and/or Voriconazole Sandoz continue to have the expected effect:
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, glyburide (used to treat diabetes);
statins, e.g. atorvastatin, simvastatin (used to lower cholesterol levels);
benzodiazepines, e.g. midazolam, triazolam (used for severe insomnia and stress);
omeprazole (used to treat peptic ulcer disease);
oral contraceptives (if Voriconazole Sandoz is used together with oral contraceptives, adverse effects such as nausea and menstrual irregularities may occur);
vinca alkaloids, e.g. vincristine, vinblastine (used to treat cancers);
tyrosine kinase inhibitors, e.g. axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib (used to treat cancers);
tretinoin (used to treat leukaemia);
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 MUST NOT be used together with Voriconazole Sandoz;
methadone (used to treat heroin addiction);
alfentanil, fentanyl and other short-acting opioids such as sufentanil (analgesics used during surgical procedures);
oxycodone and other long-acting opioids such as hydrocodone (used to treat moderate or 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 organ transplant patients);
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
Do not use Voriconazole Sandoz during pregnancy unless the doctor decides otherwise. Women of childbearing potential must use effective contraception during treatment with Voriconazole Sandoz. If the patient becomes pregnant while taking Voriconazole Sandoz, she should contact her doctor immediately.

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.

Driving and using machines
Voriconazole Sandoz may cause visual disturbances and discomfort due to light sensitivity. In such cases, driving and operating machinery should be avoided.
If such disturbances occur, contact the doctor.

Voriconazole Sandoz contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, inform the doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. the medicine is considered “sodium-free”.

3. How to use Voriconazole Sandoz

This medicine should always be used exactly as directed by your doctor or pharmacist. If in doubt,
you should consult your doctor or pharmacist.
The dose is determined by the doctor based on the patient's body weight and type of infection.
Recommended dosing for adults (including elderly patients) is provided below.

	Tablets
	Patients with body weight 40 kg and above	Patients with body weight below 40 kg
Dose during the first 24 hours (loading dose)	400 mg every 12 hours (during the first 24 hours)	200 mg every 12 hours (during the first 24 hours)
Dose after the first 24 hours (maintenance dose)	200 mg twice daily	100 mg twice daily

Depending on the patient's response to treatment, the doctor may increase the daily dose to 300 mg twice daily.
If the patient has mild or moderate liver cirrhosis, the doctor may decide to reduce the dose of the medication.
Use in children and adolescents
The recommended dosing in children and adolescents is presented below.

	Tablets
	Children aged 2 to 12 years and adolescents aged 12 to 14 years with body weight below 50 kg	Adolescents aged 12 to 14 years with body weight of 50 kg or more and individuals over 14 years of age
Dose during the first 24 hours (loading dose)	Treatment is initiated with drug administered as an infusion	400 mg every 12 hours during the first 24 hours
Dose after the first 24 hours (maintenance dose)	9 mg/kg twice daily (maximum dose 350 mg twice daily)	200 mg twice daily

Depending on the patient's response to treatment, the doctor may increase or decrease the daily dose.
 Tablets may be given to a child only if the child is able to swallow them.
The tablets should be taken at least one hour before or one hour after a meal, swallowed whole and taken with water.
If a patient receiving Voriconazole Sandoz for prevention of fungal infections experiences treatment-related adverse reactions, the doctor may discontinue administration of this medicine.
Taking more Voriconazole Sandoz than prescribed
If a patient (or anyone else) takes more tablets than prescribed, seek medical help immediately or go to the nearest hospital. Bring the Voriconazole Sandoz packaging with you. Taking more Voriconazole Sandoz than prescribed may cause light sensitivity.
Missing a dose of Voriconazole Sandoz
It is important to take Voriconazole Sandoz tablets regularly, at the same time each day. If a patient forgets to take one dose, they should take the next dose at the usual time. Do not take a double dose to make up for a missed dose.
Stopping Voriconazole Sandoz
It has been shown that taking Voriconazole Sandoz regularly at a fixed time can significantly increase its effectiveness. Therefore, it is important to use the medicine correctly as described above, unless the doctor decides to discontinue treatment.
Voriconazole Sandoz should be taken until the doctor advises stopping treatment. Do not discontinue treatment earlier, as this may result in the infection not being cured.
In patients with weakened immunity or severe infections, prolonged treatment may be necessary to prevent recurrence of the disease.
If the doctor decides to discontinue treatment with Voriconazole Sandoz, there is no need to worry about the consequences of stopping.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If an adverse reaction occurs, it is most commonly mild and transient. However, some of them
may be serious and may require medical attention.
Serious adverse reactions − immediately discontinue Voriconazole Sandoz and contact your doctor:
rash
jaundice; changes in blood test results assessing liver function
pancreatitis

Other adverse reactions

Very common (may affect more than 1 in 10 people)
visual disturbances (including blurred vision, changes in colour vision, abnormal
tolerance to light, inability to see colours, eye disturbances, seeing halos, night
blindness, sensation of vibrating images, visual aura, decreased visual acuity, bright
vision, loss of part of the normal visual field, floaters in front of the eyes)
fever
rash
nausea, vomiting, diarrhoea
headache
swelling of limbs
abdominal pain
difficulty breathing
increased liver enzyme activity

Common (may affect less than 1 in 10 people)
sinusitis, gingivitis, chills, weakness
low number of red blood cells, sometimes severe (occasionally associated with immune
response) and (or) certain types of white blood cells (sometimes with fever), low number
of blood cells called platelets, which are involved in blood clotting
low blood sugar level, low blood potassium level, low blood sodium level
anxiety, depression, confusion, agitation, insomnia, hallucinations
seizures, tremor or uncontrolled muscle movements, tingling or unusual sensations on
the skin, increased muscle tone, drowsiness, dizziness
bleeding in the eye
heart rhythm disturbances, including very fast or very slow heartbeat, fainting
low blood pressure, inflammation of veins (which may be associated with blood clots
formation)
sudden breathing difficulties, chest pain, facial swelling (oral cavity, lips, eye area), fluid
accumulation in the lungs
constipation, indigestion, inflammation of the lips
jaundice, hepatitis and liver damage
skin rash, which may progress to severe blistering and skin peeling, characterised by flat,
red areas on the skin covered with small merging bumps, skin redness
itching
hair loss
back pain
kidney failure, presence of blood in urine, changes in test results assessing kidney
function
sunburn or severe skin reaction following exposure to light or sunlight
skin cancer

Uncommon (may affect less than 1 in 100 people)
influenza-like symptoms, irritation and inflammation of the mucous membrane of the
gastrointestinal tract, antibiotic-associated diarrhoea caused by inflammation of the
gastrointestinal mucosa, vasculitis
peritonitis (inflammation of the thin membrane lining the inner wall of the abdominal
cavity and covering abdominal organs)
enlargement of lymph nodes (sometimes painful), bone marrow failure, increased number
of eosinophils
adrenal gland dysfunction, hypothyroidism
impaired brain function, symptoms resembling Parkinson's disease, nerve damage
causing numbness, pain, tingling or burning sensation in hands or feet
balance or coordination disturbances
brain swelling
double vision, severe eye disturbances, including eye pain and inflammation of eyes
and eyelids, involuntary eye movements, abnormal eye movements, optic nerve damage
leading to visual disturbances, swelling of the optic disc
decreased sensitivity to touch
taste disturbances
hearing disturbances, tinnitus, vertigo of labyrinthine origin
inflammation of certain internal organs – pancreas and duodenum
swelling and inflammation of the tongue
liver enlargement, liver failure, gallbladder disorders, gallstones
arthritis, phlebitis of subcutaneous veins (which may lead to thrombus formation)
nephritis, presence of protein in urine, kidney damage
very rapid heart rate or skipped heartbeats, sometimes with abnormal electrical impulses
abnormal electrocardiogram (ECG) findings
increased blood cholesterol level, increased blood urea level
allergic reactions (sometimes severe), including life-threatening disorder causing painful
blisters with skin and mucous membrane pain, especially in the oral cavity, skin
inflammation, urticaria, redness and skin irritation, red or purple skin discolorations
which may be caused by low platelet count, rash
allergic reaction or exacerbation of immune response
inflammation of the tissue surrounding the bone

Rare (may affect less than 1 in 1000 people)
hyperthyroidism
worsening of brain function as a severe complication of liver disease
loss of most of the optic nerve fibres, corneal opacity, involuntary eye movements
blister formation due to photosensitivity
disorder 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
skin allergic reactions (sometimes severe), including sudden swelling of the skin,
subcutaneous tissue, mucous membranes and submucosal tissues, itchy or painful
plaques of thickened, red skin with silvery scales, skin and mucous membrane
irritations, life-threatening skin disease involving detachment of large sheets of the
epidermis (outer skin layer) from deeper skin layers
appearance of small, dry, scaling skin lesions, sometimes thickened, with sharp projections
or "horns"

Adverse reactions occurring with unknown frequency:
freckles and pigmented spots

Other important adverse reactions, the frequency of which is unknown, but which should be
reported immediately to a doctor:

red, peeling skin lesions or ring-shaped skin changes, which may be symptoms of an autoimmune disease called cutaneous lupus erythematosus

Due to the known effect of Voriconazole Sandoz on the liver and kidneys, your doctor will monitor
the function of these organs by ordering appropriate blood tests. If abdominal pain or changes in
stool consistency occur, consult your doctor.
Cases of skin cancer have been reported in patients receiving Voriconazole Sandoz for a long
period.
Sunburn or severe skin reactions following exposure to light or sunlight occurred more frequently
in children. If skin disorders occur, the doctor may refer the patient to a dermatologist, who after
consultation may decide on the need for regular follow-up visits. Increased liver enzyme activity
has also been observed more frequently in children.
If any of these adverse reactions persist or are troublesome for the patient, inform your doctor.

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

5. How to store Voriconazole Sandoz

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack, carton, and bottle
following “EXP”. The expiry date refers to the last day of the stated month.
No special storage conditions required.
Medicines should 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 pack and other information

What Voriconazole Sandoz contains

The active substance is voriconazole. Each film-coated tablet contains 200 mg of voriconazole.
The other ingredients are:
Tablet core: monohydrate lactose, maize starch gelatinised, sodium croscarmellose, povidone K-30, magnesium stearate
Tablet coating (Opadry II White 33K58715): hypromellose 6 cP, monohydrate lactose, titanium dioxide (E 171), triacetin

What Voriconazole Sandoz looks like and contents of the pack
White or almost white, biconvex film-coated tablets in capsule shape, with the number '200' embossed on one side and smooth on the other.
The tablets are packed in PVC/PVDC/Aluminium blisters and placed in a cardboard box.
Pack sizes:
20, 28, 30, 56, 60 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria

Manufacturer/Importer
Lek Pharmaceuticals d.d.
Verovškova 57
1526 Ljubljana, Slovenia
Lek S.A.
ul. Domaniewska 50 C
02-672 Warszawa, Poland
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany
S.C. Sandoz, S.R.L.
Str. Livezeni nr 7A
RO-540472 Targu-Mures, Romania
Lek Pharmaceuticals d.d.,
Trimlini 2d,
9220 Lendava, Slovenia

For further information about the medicinal product and its names in other European Economic Area member states, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa, Poland
tel. 22 209 70 00