Voriconazole Aurobindo: detailed information

Patient Information Leaflet

Voriconazole Aurobindo 50 mg film-coated tablets, 200 mg film-coated tablets

Generic medicine
Please read this leaflet carefully before taking this medicine, as 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Voriconazolo Aurobindo is and what it is used for

Voriconazolo Aurobindo contains the active substance voriconazole. Voriconazolo Aurobindo is an antifungal medicine. It works by stopping the growth of, or killing, the 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 and Fusarium (two different types of fungi).

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

2. What you should know before taking Voriconazole Aurobindo

Do not take Voriconazole Aurobindo:
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 medicines.
The medicines listed below must not be used during treatment with
Voriconazole Aurobindo:

Terfenadine (for allergies).
Astemizole (for allergies).
Cisapride (for stomach problems).
Pimozide (for the treatment of mental illnesses).
Quinidine (for irregular heartbeat).
Ivabradine (for symptoms of chronic heart failure).
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; for migraine).
Sirolimus (for transplant patients).
Ritonavir (for the treatment of AIDS) at doses of 400 mg or more, twice daily.
St. John’s Wort (Hypericum perforatum – a herbal supplement).
Naloxegol (for the treatment of constipation specifically caused by opioid pain medicines [e.g. morphine, oxycodone, fentanyl, tramadol, codeine]).
Tolvaptan (for the treatment of hyponatraemia, i.e. low sodium levels in the blood, or to slow the decline in kidney function in patients with polycystic kidney disease).
Lurasidone (for the treatment of depression).
Venetoclax (for the treatment of patients with chronic lymphocytic leukaemia - CLL).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Voriconazole Aurobindo if:

you have had an allergic reaction to other azole antifungals.
you have or have had liver disease. If you have liver problems, your doctor may prescribe a lower dose of Voriconazole Aurobindo. Your doctor will need to monitor your liver function during treatment with Voriconazole Aurobindo by performing blood tests.
you know you have heart disease, irregular heartbeat, slow heartbeat, or an abnormality on electrocardiogram (ECG) called “long QTc syndrome”.

You must avoid any exposure to sunlight and UV light during treatment. It is important to cover exposed skin areas and use sunscreens with high protection factor (SPF), as increased sensitivity of the skin to UV light may occur. 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 Aurobindo:

inform your doctor immediately if you develop sunburn; or severe skin reaction or blistering; or bone pain.

If you develop any of the skin conditions described above, your doctor may refer you to a dermatologist, who after evaluation may decide that regular follow-up visits are necessary. With long-term use of Voriconazole Aurobindo, there is a small risk of developing skin cancer.
If you develop signs of “adrenal insufficiency”, where the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol, which may cause symptoms such as chronic or persistent fatigue, muscle weakness, loss of appetite, weight loss, or abdominal pain, inform your doctor.
Inform your doctor if you develop signs of “Cushing’s syndrome”, where the body produces excessive amounts of the hormone cortisol, which may cause symptoms such as weight gain, fat accumulation between the shoulders, rounded face, darkening of the skin on the abdomen, thinning of legs, breasts, and arms, thinning of the skin, easy bruising, increased blood sugar levels, excessive body hair growth, and excessive sweating.
Your doctor will need to monitor your liver and kidney function through blood tests.

Children and adolescents
Voriconazole Aurobindo must not be given to children under 2 years of age.

Other medicines and Voriconazole Aurobindo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Some medicines, when taken together with Voriconazole Aurobindo, may alter the effect of Voriconazole Aurobindo, or Voriconazole Aurobindo may alter the effect of these medicines.
Inform your doctor if you are taking the following medicine, because concomitant treatment with Voriconazole Aurobindo should be avoided if possible:

Ritonavir (for the treatment of AIDS) at doses of 100 mg twice daily.
Glasdegib (for the treatment of cancer): if you need to use both medicines, your doctor will frequently monitor your heart rhythm. Inform your doctor if you are taking either of these two medicines because concomitant treatment with Voriconazole Aurobindo should be avoided if possible, and a dose adjustment of voriconazole may be necessary:
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 Aurobindo, and your dose may need to be adjusted.

Inform your doctor if you are taking any of the following medicines, as dose adjustments or monitoring may be necessary to ensure these medicines and/or Voriconazole Aurobindo continue to have the desired effect:

Warfarin and other anticoagulants (e.g. phenprocoumon, acenocoumarol; to slow down blood clotting).
Ciclosporin (for transplant patients).
Tacrolimus (for transplant patients).
Sulfonylureas (e.g. tolbutamide, glipizide, glibenclamide) (for diabetes).
Statins (e.g. atorvastatin, simvastatin) (to reduce cholesterol).
Benzodiazepines (e.g. midazolam, triazolam) (for severe insomnia and anxiety).
Omeprazole (for the treatment of ulcers).
Oral contraceptives (if you take Voriconazole Aurobindo while using oral contraceptives, side effects such as nausea and menstrual disturbances may occur).
Vinca alkaloids (e.g. vincristine, vinblastine) (for the treatment of cancer).
Tyrosine kinase inhibitors (e.g. axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (for the treatment of cancer).
Tretinoin (for the treatment of leukaemia).
Indinavir and other protease inhibitors for AIDS (for the treatment of AIDS).
Non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz, delavirdine, nevirapine) (for the treatment of AIDS) (some doses of efavirenz cannot be taken together with Voriconazole Aurobindo).
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 (NSAIDs) (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 renal cell carcinoma and in transplant patients).
Letermovir (used to prevent cytomegalovirus (CMV) disease following allogeneic haematopoietic stem cell transplantation).
Ivacaftor: used for the treatment of cystic fibrosis.
Flucloxacillin (an antibiotic indicated for bacterial infections).

Pregnancy and breastfeeding
Voriconazole Aurobindo must not be taken during pregnancy unless specifically decided by your doctor. Women of childbearing potential must use an adequate method of contraception. Contact your doctor immediately if you become pregnant during treatment with Voriconazole Aurobindo.
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
Voriconazole Aurobindo may cause blurred vision or increased sensitivity to light. In such cases, you should not drive and should not operate tools or machinery. In these cases, contact your doctor.

Voriconazole Aurobindo contains lactose
If your doctor has informed you that you have an intolerance to certain sugars, contact him/her before taking this medicine.

Voriconazole Aurobindo contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. essentially ‘sodium-free’.

3. How to take Voriconazole Aurobindo

Take this medicine exactly as directed by your doctor. 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:

	Tablets
	Patients weighing 40 kg or more	Patients weighing less than 40 kg
Dose for the first 24 hours (Loading dose)	400 mg every 12 hours for the first 24 hours	200 mg every 12 hours for the first 24 hours
Dose after the first 24 hours (Maintenance dose)	200 mg twice daily	100 mg twice daily

Based on the response to treatment, your doctor may increase the daily dose to 300 mg twice a day.
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:

	Tablets
	Children aged 2 to less than 12 years and adolescents aged 12 to 14 years with body weight below 50 kg	Adolescents aged 12 to 14 years with body weight equal to or greater than 50 kg; all adolescents older than 14 years
Dose for the first 24 hours (Loading dose)	Treatment will be initiated as an infusion	400 mg every 12 hours for the first 24 hours
Dose after the first 24 hours (Maintenance dose)	9 mg/kg twice daily (maximum dose is 350 mg twice daily)	200 mg twice daily

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 some water.
If you or your child is taking Voriconazole Aurobindo for the prevention of fungal infections, you may decide to discontinue the administration of Voriconazole Aurobindo if you or your child develops treatment-related adverse effects.

If you take more Voriconazole Aurobindo than you should
If you take more tablets than prescribed (or if someone else takes your tablets), contact your doctor or go immediately to the nearest emergency department. Take the pack of Voriconazole Aurobindo tablets with you. You may experience abnormal intolerance to light if you take more Voriconazole Aurobindo than you should.

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

If you stop taking Voriconazole Aurobindo
It has been shown that taking doses at the correct times can significantly increase the effectiveness of your medicine. Therefore, unless your doctor has told you to stop treatment, it is important to continue taking Voriconazole Aurobindo correctly as described above.
Continue taking Voriconazole Aurobindo until your doctor tells you to stop treatment. Do not stop treatment prematurely, 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 Aurobindo is stopped at the doctor's instruction, no withdrawal effects should occur.

If you have any doubts about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If side effects occur, most will probably be mild and temporary. However, some may be serious and require medical attention.
Serious side effects – Stop taking Voriconazole Aurobindo and consult a doctor immediately

Rash.
Jaundice, abnormal liver function tests.
Pancreatitis.

Other side effects
Very common: may occur in more than 1 in 10 people

Visual disturbances (vision disorders including blurred vision, altered colour vision, abnormal visual perception of light, colour blindness, eye disorders, seeing halos, night blindness, oscillating vision, seeing sparks, visual aura, reduced visual acuity, visual brightness, partial loss of visual field, spots in front of the eyes).
Fever.
Rash.
Nausea, vomiting, diarrhoea.
Headache.
Swelling of extremities.
Stomach pain.
Difficulty breathing.
Elevated liver enzymes.

Common: may occur in up to 1 in 10 people

Sinus inflammation, gum inflammation, chills, fatigue.
Reduction, sometimes severe, in the number of certain types of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes with fever), reduction in the number of blood cells called platelets that help blood clotting.
Low blood sugar levels, low blood potassium levels, low blood sodium levels.
Anxiety, depression, confusion, agitation, sleep disorders, hallucinations.
Seizures, tremor or uncontrolled muscle movements, tingling or abnormal skin sensations, increased muscle tone, drowsiness, dizziness.
Bleeding in the eye.
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 difficulty, chest pain, facial swelling (mouth, lips and around the eyes), fluid accumulation in the lungs.
Constipation, indigestion, inflammation of the lips.
Jaundice, liver inflammation and liver damage.
Rash which may lead to blistering and severe skin peeling, characterised by flat red areas of skin 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 reaction following exposure to light or sun.
Skin cancer.

Uncommon: may occur in up to 1 in 100 people

Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, inflammation of the gastrointestinal tract which may cause antibiotic-associated diarrhoea, inflammation of lymphatic vessels.
Inflammation of the thin membrane lining the abdominal wall and covering abdominal organs.
Enlarged lymph nodes (sometimes painful), bone marrow failure, increased eosinophils.
Reduced adrenal gland function, reduced thyroid gland activity.
Changes in brain function, Parkinson-like symptoms, nerve damage leading to numbness, pain, tingling or burning in hands or feet.
Balance and coordination problems.
Brain oedema.
Double vision, serious eye conditions including: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage with visual impairment, swelling of the optic disc.
Reduced sensitivity to touch.
Taste disturbances.
Hearing disorders, ringing in the ears, vertigo.
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 clots).
Kidney inflammation, presence of protein in urine, kidney damage.
Very rapid heartbeat or missed beats, sometimes with irregular electrical impulses.
Abnormal electrocardiogram (ECG).
Increased cholesterol, increased blood urea.
Allergic skin reactions (sometimes severe), including potentially life-threatening skin condition causing blisters and painful sores of the skin and mucous membranes, especially in the mouth, skin inflammation, urticaria, skin redness and irritation, red or purplish skin discolouration which may be caused by low platelet count, eczema.
Infusion site reaction.
Allergic reactions or exaggerated immune response.
Inflammation of tissues surrounding bones.

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

Overactive thyroid gland.
Deterioration of brain function as a serious complication of liver disease.
Loss of most of the optic nerve fibres, corneal opacity, involuntary eye movement.
Bullous photosensitivity.
Disorder in which the body's immune system attacks part of the peripheral nervous system.
Heart rhythm or conduction problems (sometimes fatal).
Potentially life-threatening allergic reaction.
Coagulation disorders.
Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues, itchy or painful patches of thickened, red skin with silvery scales, skin and mucous membrane irritation, a potentially life-threatening skin condition causing detachment of large areas of the epidermis, the outermost skin layer, from underlying skin layers.
Small patches of dry, scaly skin, sometimes thickened, with tips or “horns”.

Side effects whose frequency is not known

Freckles and pigmented spots.

Other significant side effects, whose frequency is not known but which must be reported to a doctor immediately, are:

Red, scaly patches or ring-shaped skin lesions which could be symptoms of an autoimmune disease called systemic lupus erythematosus. Since Voriconazole Aurobindo has been observed to affect the liver and kidneys, your doctor will need to monitor liver and kidney function through blood tests. Inform your doctor if you have stomach pain or if your stools have an unusual consistency.

Cases of skin carcinoma have been reported in patients treated with Voriconazole Aurobindo for prolonged periods.
Sunburn or a severe skin reaction following exposure to light or sun has been reported more frequently in children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist who may decide whether regular dermatological follow-up is 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 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 Aurobindo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of that month.
This medicine requires no 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 Aurobindo contains

The active substance is voriconazole. Each film-coated tablet contains 50 mg of voriconazole. Each film-coated tablet contains 200 mg of voriconazole.
The other components are: Tablet core: monohydrate lactose, pregelatinized corn starch (corn starch), corn starch, sodium croscarmellose, povidone (K-30), anhydrous colloidal silica, magnesium stearate. Tablet coating: hypromellose 2910, monohydrate lactose, titanium dioxide (E171), triacetin.

Description of the appearance of Voriconazolo Aurobindo and package contents
Film-coated tablets.
Voriconazolo Aurobindo 50 mg film-coated tablets
White, round, biconvex, film-coated tablet marked with “CC” on one side and “52” on the other side.
Voriconazolo Aurobindo 200 mg film-coated tablets
White, oval-shaped, biconvex, film-coated tablet marked with “CC” and “56” separated by a breakline on one side and smooth on the other side. The tablet can be divided into two equal doses.
Voriconazolo Aurobindo film-coated tablets are available in PVC blisters/aluminum foil packs containing 28 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Aurobindo Pharma (Italia) S.r.l., via San Giuseppe 102, 21047 Saronno (VA), Italy

Manufacturers
APL Swift Services (Malta) Limited HF26, Hal Far Industrial Estate, Hal Far, Birzebbugia, BBG 3000, Malta

This medicinal product is authorized in the European Economic Area countries under the following names:
Italy: Voriconazolo Aurobindo