VORICONAZOLE MYLAN

Patient Information Leaflet

Voriconazolo Mylan 50 mg film-coated tablets, 200 mg film-coated tablets

Voriconazole
Generic medicine
Please read 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Voriconazolo Mylan is and what it is used for
2. What you need to know before taking Voriconazolo Mylan
3. How to take Voriconazolo Mylan
4. Possible side effects
5. How to store Voriconazolo Mylan
6. Contents of the pack and other information

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

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

• Invasive aspergillosis (a type of fungal infection caused by species of Aspergillus)
• Candidaemia (another type of fungal infection caused by species of Candida) in non-neutropenic patients (patients who do not have an unusually low white blood cell count)
• Serious and invasive infections caused by species of Candida when the fungus is resistant to fluconazole (another antifungal medicine)
• Serious fungal infections caused by species of Scedosporium or Fusarium (two different species of fungi).

Voriconazole Mylan is indicated for patients with worsening fungal infections that are potentially life-threatening.
Prevention of fungal infections in patients undergoing bone marrow transplantation who are at high risk.
This medicine should only be used under medical supervision.

2. What you need to know before taking Voriconazole Mylan

Do not take Voriconazole Mylan

• If you are allergic to voriconazole or to any of the other ingredients of this medicine (listed in section 6).

It is very important that you inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those without a prescription, or herbal remedies.
The following medicines must not be used during treatment with Voriconazole Mylan:

• Terfenadine (for allergies)
• Astemizole (for allergies)
• Cisapride (for stomach problems)
• Pimozide (for the treatment of mental illnesses)
• Ivabradine (used for symptoms of chronic heart failure)
• Quinidine (for irregular heartbeat)
• Rifampicin (for the treatment of tuberculosis)
• Efavirenz (for the treatment of AIDS) at doses equal to or greater than 400 mg once daily
• Carbamazepine (for the treatment of seizures)
• Phenobarbital (for severe insomnia and seizures)
• Ergot alkaloids (e.g. ergotamine, dihydroergotamine; used for migraine)
• Sirolimus (in organ transplant patients)
• Ritonavir (for the treatment of AIDS) at doses of 400 mg or more, twice daily
• St. John’s Wort (herbal supplement)
• Naloxegol (used to treat constipation specifically caused by painkillers called opioids, e.g. morphine, oxycodone, fentanyl, tramadol, codeine)
• Tolvaptan (used to treat hyponatraemia (low sodium levels in the blood) or to slow the decline in kidney function in patients with polycystic kidney disease)
• Lurasidone (used to treat depression)
• Venetoclax (used for the treatment of patients with chronic lymphocytic leukaemia - CLL)
• Warnings and precautions Talk to your doctor, pharmacist or nurse before taking Voriconazole Mylan if:
  • you have had an allergic reaction to other azoles
  • you have or have had liver disease. If you have liver disease, your doctor may prescribe a lower dose of Voriconazole Mylan. Your doctor should monitor liver function during treatment with Voriconazole Mylan by performing blood tests.
  • you know you have cardiomyopathy, irregular heartbeat, slow heart rate, or an abnormality on electrocardiogram (ECG) called “prolonged QTc syndrome”.

You must avoid any exposure to sunlight and UV light during treatment. It is important to cover exposed skin areas and use high-protection sunscreens (SPF), as skin sensitivity to UV rays may increase. This risk may be further 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 Mylan:
inform your doctor immediately if you develop:

• Sunburn
• Severe skin reaction or blistering
• Bone pain

If you develop any of the skin conditions described above, your doctor may refer you to a dermatologist, who after consultation may decide that regular check-ups are necessary. With long-term use of Voriconazole Mylan, there is a small risk of developing skin carcinoma.
If you develop signs of "adrenal insufficiency", in which the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol, which may lead to symptoms such as: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.
If you develop signs of "Cushing's syndrome", in which the body produces excessive amounts of the hormone cortisol, which may lead to symptoms such as: weight gain, fatty hump between the shoulders, rounded face, darkening of the skin on the stomach, thighs, breasts and arms, thin skin, easy bruising, high blood sugar, excessive hair growth, excessive sweating, inform your doctor.
Your doctor should monitor liver and kidney function by performing blood tests.
Children and adolescents
Voriconazole Mylan must not be given to children under 2 years of age.
Other medicines and Voriconazole Mylan
Please inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription.
Some medicines, when taken together with Voriconazole Mylan, may alter the effect of Voriconazole Mylan or Voriconazole Mylan may alter the effect of these medicines.
Inform your doctor if you are taking the following medicine because concomitant treatment with Voriconazole Mylan should be avoided, if possible:

• Ritonavir (for the treatment of AIDS) at doses of 100 mg twice daily
• Glasdegib (used for the treatment of cancer): if both medicines must be used, your doctor will frequently monitor your heart rate.

Inform your doctor if you are taking any of the following medicines because concomitant treatment with Voriconazole Mylan should be avoided, if possible, and a dose adjustment of voriconazole may be required:

• Rifabutin (for the treatment of tuberculosis). If you are already being treated with rifabutin, blood cell counts and rifabutin-related side effects should be closely monitored.
• Phenytoin (for the treatment of epilepsy). If you are already being treated with phenytoin, blood levels of phenytoin should be monitored during treatment with Voriconazole Mylan and your dose may need to be adjusted.

Inform your doctor if you are taking any of the following medicines because a dose adjustment or monitoring may be needed to ensure these medicines and/or Voriconazole Mylan remain effective:

• Warfarin and other anticoagulants (e.g. phenprocoumon, acenocoumarol; to slow down blood clotting)
• Cyclosporine (in organ transplant patients)
• Tacrolimus (in organ transplant patients)
• Sulfonylureas (e.g. tolbutamide, glipizide, glimepiride) (for diabetes)
• Statins (e.g. atorvastatin, simvastatin) (to reduce cholesterol)
• Benzodiazepines (e.g. midazolam, triazolam, alprazolam) (for severe insomnia and stress)
• Omeprazole (for the treatment of ulcers)
• Oral contraceptives (if you take Voriconazole Mylan while using oral contraceptives, side effects such as nausea and menstrual disorders may occur)
• Vinca alkaloids (e.g. vincristine, vinblastine) (for cancer treatment)
• Tyrosine kinase inhibitors (e.g. axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used for cancer treatment)
• Tretinoin (used to treat leukaemia)
• Indinavir and other HIV protease inhibitors (for the treatment of AIDS)
• Non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz, delavirdine, nevirapine) (for the treatment of AIDS) (some doses of efavirenz must NOT be taken together with Voriconazole Mylan)
• Methadone (for the treatment of heroin addiction)
• Alfentanil and fentanyl and other short-acting opioids such as sufentanil (analgesics used in surgical procedures)
• Oxycodone and other long-acting opioids such as hydrocodone (used for the treatment of moderate to severe pain)
• Non-Steroidal Anti-Inflammatory Drugs (e.g. ibuprofen, diclofenac) (used for the treatment of pain and inflammation)
• Fluconazole (used to treat fungal infections)
• Everolimus (used for the treatment of advanced kidney cancer and in transplant patients)
• Letermovir (used to prevent cytomegalovirus (CMV) disease after bone marrow transplant)
• Ivacaftor: used for the treatment of cystic fibrosis
• • Flucloxacillin (an antibiotic used against bacterial infections) Pregnancy and breastfeeding Voriconazole Mylan must not be taken during pregnancy unless specifically decided by your doctor. Women of childbearing age must use an adequate contraceptive method. Contact your doctor immediately if you become pregnant while being treated with Voriconazole Mylan. If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking any medicine.

Driving and using machines
Voriconazole Mylan may cause blurred vision, altered visual perception or increased sensitivity to light. In such cases, you must not drive or operate tools or machinery. In these cases, contact your doctor.
Voriconazole Mylan contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per 50 mg tablet, i.e. it is essentially “sodium-free”.
This medicine contains less than 1 mmol of sodium (23 mg) per 200 mg tablet, i.e. it is essentially “sodium-free”.

3. How to take Voriconazole Mylan

Take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the appropriate dose for you based on your body weight and the type of infection diagnosed.
The recommended dose for adults (including elderly patients) is as follows:

Depending on the response to treatment, your doctor may increase the daily dose to 300 mg twice daily.
If you have mild to moderate cirrhosis, your doctor may decide to reduce the dose.
Use in children and adolescents
The recommended dose in children and adolescents is as follows:

Depending on the response to treatment, your doctor may increase or decrease the daily dose.
The tablets should only be administered if the child is able to swallow tablets.
Take the tablets at least one hour before or one hour after meals. Swallow the tablet whole with a little water.
If you or your child is taking Voriconazole Mylan for prevention of fungal infections, your doctor may decide to discontinue the administration of Voriconazole Mylan if you or your child develops treatment-related adverse effects.

If you take more Voriconazole Mylan than you should
If you take more tablets than prescribed (or if someone else takes your tablets), contact your doctor immediately or go to the nearest emergency department. Take the Voriconazole Mylan tablet pack with you. Abnormal light sensitivity may occur if you take more Voriconazole Mylan than you should.

If you forget to take Voriconazole Mylan
It is important to take Voriconazole Mylan tablets regularly every day at the same time. If you forget to take a dose, take the next dose at the scheduled time. Do not take a double dose to make up for the missed dose.

If you stop taking Voriconazole Mylan
It has been shown that taking doses at the correct time can significantly increase the effectiveness of the medicine. Therefore, unless your doctor has instructed you to stop treatment, it is important to continue taking Voriconazole Mylan correctly as described above.
Continue taking Voriconazole Mylan until your doctor tells you to stop. Do not stop treatment earlier than advised, as the infection may not be cured. Patients with a weakened immune system or those with difficult-to-treat infections may require long-term treatment to prevent the infection from returning.
When treatment with Voriconazole Mylan is discontinued as directed by your doctor, no adverse effects should occur.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

If side effects occur, most are likely to be minor and temporary.
However, some may be serious and require medical attention.
Serious side effects – Stop taking Voriconazole Mylan and consult a doctor immediately

• Rash
• Jaundice; Changes in blood tests for liver function
• Pancreatitis

Other side effects
Very common (may affect more than 1 in 10 people)

• Visual disturbance (vision changes including blurred vision, color vision abnormalities, abnormal sensitivity to light, color blindness, eye disorders, seeing halos, night blindness, fluctuating vision, seeing sparks, visual aura, reduced visual acuity, visual brightness, loss of part of the normal visual field, spots in front of the eyes)
• Fever
• Rash
• Nausea, vomiting, diarrhoea
• Headache
• Swelling of extremities
• Stomach pain
• Breathing difficulties
• Elevated liver enzymes

Common (may affect up to 1 in 10 people)

• Sinus inflammation, gum inflammation, chills, weakness
• Low levels of certain types, sometimes severe, of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes with fever), low levels of platelets (blood cells that help blood to clot)
• Low blood sugar, low blood potassium, low blood sodium
• Anxiety, depression, confusion, agitation, insomnia, hallucinations
• Seizures, tremors or uncontrolled muscle movements, tingling or abnormal skin sensations, increased muscle tone, drowsiness, dizziness
• Bleeding in the eyes
• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting
• Low blood pressure, inflammation of a vein (which may be associated with blood clot formation)
• Acute breathing difficulties, chest pain, facial swelling (mouth, lips and around eyes), fluid accumulation in the lungs
• Constipation, indigestion, inflammation of the lips
• Jaundice, liver inflammation and liver damage
• Skin rashes that may lead to severe blistering and peeling of the skin, characterized by flat red areas on the skin, skin covered with small merging bumps, skin redness
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in urine, changes in kidney function tests
• Sunburn or severe skin reactions after exposure to light or sun, skin cancer

Uncommon (may affect up to 1 in 100 people)

• Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, gastrointestinal inflammation causing antibiotic-associated diarrhoea, inflammation of lymphatic vessels
• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs
• Enlarged lymph nodes (sometimes painful), bone marrow failure, increased eosinophils
• Impaired adrenal gland function, underactive thyroid
• Abnormal brain function, Parkinson-like symptoms, nerve damage leading to numbness, pain, tingling or burning in hands or feet
• Problems with balance or coordination
• Brain swelling
• Double vision, serious eye conditions including: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage leading to vision impairment, swelling of the optic disc
• Decreased sensitivity to touch
• Abnormal sense of taste
• Hearing difficulties, ringing in the ears, dizziness
• Inflammation of certain internal organs: pancreas and duodenum, swelling and inflammation of the tongue
• Enlarged liver, liver failure, gallbladder diseases, gallstones
• Joint inflammation, inflammation of subcutaneous veins (which may be associated with blood clot formation)
• Kidney inflammation, protein in urine, kidney damage
• Very rapid heartbeat or skipped heartbeats, sometimes with irregular electrical impulses
• Abnormal electrocardiogram (ECG)
• Increased blood cholesterol, increased blood urea
• Allergic skin reactions (sometimes severe), including life-threatening skin conditions causing
• blisters and painful sores of the skin and mucous membranes, especially in the mouth, skin inflammation, hives, redness and irritation of the skin, red or purple skin discoloration that may be caused by low platelet count, eczema
• Reaction at the infusion site
• Allergic reaction or exaggerated immune response
• Inflammation of the tissue surrounding the bone

Rare (may affect up to 1 in 1,000 people)

• Overactive thyroid gland
• Deterioration of brain function, a serious complication of liver disease
• Loss of most of the optic nerve fibres, corneal opacity, involuntary eye movement
• Bullous photosensitivity
• A disorder in which the body's immune system attacks part of the peripheral nervous system
• Heart rhythm or conduction problems (sometimes life-threatening)
• Life-threatening allergic reaction
• Blood clotting disorder
• Skin allergic reactions (sometimes severe), including rapid swelling (edema) of the dermis, subcutaneous tissue, mucous membranes and submucosal tissues, itchy or painful thickened red skin patches with silvery scales, skin and mucous membrane irritation, life-threatening skin condition causing detachment of large portions of the epidermis, the outermost skin layer, from underlying skin layers
• Small dry scaly skin patches, sometimes thickened, with tips or "horns"

Adverse events with unknown frequency:

• Freckles and pigmented spots

Other significant adverse effects with unknown frequency, but which must be reported immediately to a doctor:
Red, scaly patches or ring-shaped skin lesions which may be a symptom of an autoimmune disease called cutaneous lupus erythematosus.

Since voriconazole is known to affect the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. Please inform your doctor if you experience stomach pain or if your stools have an unusual consistency.
Cases of skin cancer have been reported in patients treated with voriconazole over a long period.
Sunburn or severe skin reactions following exposure to light or sun have been observed more frequently in children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist, who after consultation may decide whether regular follow-up visits are necessary for you or your child.
Elevated liver enzymes have also been observed more frequently in children.
If any of these side effects persist or are bothersome, inform your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Voriconazole Mylan

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 blister after
EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Voriconazolo Mylan contains

• The active substance is voriconazole. Each tablet contains 50 mg or 200 mg of voriconazole.
• The other components are: Tablet core: Lactose (see section 2 “Voriconazolo Mylan contains monohydrate lactose and sodium”), sodium croscarmellose, pregelatinized corn starch, povidone, and magnesium stearate. Coating: Monohydrate lactose, hypromellose, titanium dioxide (E171), and triacetin.

Description of the appearance of Voriconazolo Mylan and contents of the pack
Voriconazolo Mylan 50 mg film-coated tablets: Film-coated tablets, white to off-white, oval, biconvex, with "V26" engraved on one side of the tablet and smooth on the other side.
Voriconazolo Mylan 200 mg film-coated tablets: Film-coated tablets, white to off-white, capsule-shaped, biconvex, with "M164" engraved on one side of the tablet and smooth on the other side.
Voriconazolo Mylan is available in blister packs containing:
20, 28, 30, 90, 100, 28 x 1, 30 x 1, 50 x 1, 56 x 1, 60 x 1, 100 x 1 film-coated tablets
for Voriconazolo Mylan 50 mg film-coated tablets.
14, 20, 28, 30, 90, 100, 14 x 1, 28 x 1, 30 x 1, 50 x 1, 56 x 1, 60 x 1, 100 x 1
for Voriconazolo Mylan 200 mg film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milano, Italy

Manufacturers
GE Pharmaceuticals Ltd., Industrial Zone, Chekanitza-South area, 2140 Botevgrad, Bulgaria
Mylan Hungary Kft., H-2900 Komárom, Mylan utca 1, Hungary

This medicinal product is authorized in the European Economic Area countries under the following names:
France: Voriconazole Viatris 50 mg and 200 mg, comprimé pelliculé
Italy: Voriconazolo Mylan
Netherlands: Voriconazol Viatris 50 mg and 200 mg, filmomhulde tabletten
Portugal: Voriconazol Mylan
Czech Republic: Vorikonazol Viatris 200 mg, potahované tablety