Voriconazole Accord 50mg film-coated tablets

2. What you need to know before you take Voriconazol Accord

Do not take Voriconazol Accord

• if you are allergic to voriconazole or 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 using or have recently used other medicines, including those obtained without a prescription, or herbal remedies.

During treatment with Voriconazol Accord, you must not take the following medicines:

• Terfenadine (used for allergy).
• Astemizole (used for allergy).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for cardiac arrhythmias).
• Rifampicin (used for the treatment of tuberculosis).
• Efavirenz (used for the treatment of HIV) at doses of 400 mg and above once daily.
• Carbamazepine (used to treat seizures).
• Phenobarbital (used for severe insomnia and seizures).
• Ergot alkaloids (e.g. ergotamine, dihydroergotamine; used for migraine).
• Sirolimus (used in patients who have received a transplant).
• Ritonavir (used for the treatment of HIV) at doses of 400 mg and above twice daily.
• St. John's Wort (hypericum, herbal remedy).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting Voriconazol Accord 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 Voriconazol Accord. Your doctor should also monitor your liver function while you are being treated with Voriconazol Accord with blood tests.
• you know that you have cardiomyopathy, irregular heartbeats, slow heartbeat, or an abnormality in the electrocardiogram (ECG) called "QTc prolonged syndrome".

You should avoid any exposure to the sun and sunlight during treatment. It is important that you cover exposed areas and use a sunscreen with a high sun protection factor (SPF), as you may experience increased sensitivity of the skin to the sun's UV rays. These precautions also apply to children.

While you are being treated with Voriconazol Accord:

• tell your doctor if you experience

• sunburn
• severe skin rash or blisters
• bone pain

If you develop skin disorders such as those described above, your doctor may refer you to a dermatologist, who after consultation may consider it important that you are examined regularly. There is a small probability that you may develop skin cancer with long-term use of Voriconazol Accord.

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

Children and adolescents

Voriconazol Accord should not be given to children under 2 years of age.

Taking Voriconazol Accord with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take other medicines, including those obtained without a prescription.

Some medicines, when used at the same time as Voriconazol Accord, can affect the action of Voriconazol Accord or Voriconazol Accord may affect the action of other medicines.

Tell your doctor if you are using the following medicines, as concurrent treatment with Voriconazol Accord should be avoided if possible:

• Ritonavir (used for the treatment of HIV) at doses of 100 mg twice daily.

Tell your doctor if you are using any of the following medicines, as it is recommended to avoid concurrent treatment with Voriconazol Accord whenever possible, and a dose adjustment of voriconazole may be necessary:

• Rifabutin (used for the treatment of tuberculosis). If you are already being treated with rifabutin, your blood count and rifabutin side effects should be monitored. Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, your phenytoin blood levels should be monitored during treatment with Voriconazol Accord and your dose may need to be adjusted.

Tell your doctor if you are taking any of the following medicines, as you may need a dose adjustment or monitoring to check that these medicines and/or Voriconazol Accord are still working:

• Warfarin and other anticoagulants (e.g. phenprocoumon, acenocoumarol; used to decrease blood clotting).
• Cyclosporine (used in patients who have received a transplant).
• Tacrolimus (used in patients who have received a transplant).
• Sulfonylureas (e.g. tolbutamide, glipizide, and gliburide) (used for diabetes).
• Statins (e.g. atorvastatin, simvastatin) (used to lower cholesterol levels).
• Benzodiazepines (e.g. midazolam, triazolam) (used for severe insomnia and stress).
• Omeprazole (used for the treatment of stomach ulcers).
• Oral contraceptives (if you take Voriconazol Accord while using oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vinca alkaloids (e.g. vincristine and vinblastine) (used to treat cancer).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• Non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz, delavirdine, and nevirapine) (used to treat HIV infection) (some doses of efavirenz should NOT be taken at the same time as Voriconazol Accord).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opiates such as sufentanil (painkillers used for operations).
• Oxycodone and other long-acting opiates such as hydrocodone (used to treat moderate to severe pain).
• Non-steroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac) (used to treat pain and inflammation).
• Fluconazole (used to treat fungal infections).
• Everolimus (used to treat advanced kidney cancer and in patients who have received a transplant).

Pregnancy and breastfeeding

Do not take Voriconazol Accord during pregnancy unless your doctor has told you to. Women of childbearing age taking Voriconazol Accord should use effective contraception.

Contact your doctor immediately if you become pregnant during treatment with Voriconazol Accord.

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

Driving and using machines

Voriconazol Accord may cause blurred vision or sensitivity to light. If this happens, do not drive or use tools or machines and tell your doctor.

Voriconazol Accord contains lactose

If your doctor has told you that you have an intolerance to some sugars, talk to your doctor before taking Voriconazol Accord.

3. How to take Voriconazol Accord

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

Your doctor will determine the dose depending on your weight and the type of infection you have.

The recommended dose in adults (including elderly patients) is as follows:

Depending on your response to treatment, your doctor may increase the daily dose to 300 mg twice daily.

Your doctor may decide to reduce the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

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

• Tablets should only be given if the child is able to swallow whole tablets.

Take the tablets at least one hour before or one hour after a meal. Swallow the tablet whole with a little water.

If you or your child are taking Voriconazol Accord to prevent fungal infections, your doctor may stop the administration of Voriconazol Accord if you or your child experience treatment-related side effects.

If you take more Voriconazol Accord than you should

If you take more tablets than you have been told to (or if someone else takes your tablets), immediately contact a doctor or go to the nearest hospital casualty department. Take the pack of Voriconazol Accord tablets with you. You may notice abnormal sensitivity to light as a result of taking more Voriconazol Accord than you should.

If you forget to take Voriconazol Accord

It is important to take the tablets of Voriconazol Accord regularly at the same time each day. If you forget to take a dose, take the next dose when it is due. Do not take a double dose to make up for a forgotten dose.

If you stop taking Voriconazol Accord

It has been shown that strictly following the prescribed dosage, taking each dose at the right time, can significantly increase the effectiveness of this medicine. Therefore, unless your doctor tells you to stop treatment, it is important that you continue taking Voriconazol Accord correctly, as previously indicated.

Continue taking Voriconazol Accord until your doctor tells you to stop. Do not stop treatment early, as the infection may not be fully treated. Patients with compromised immune systems or complicated infections may require longer treatment to prevent the infection from coming back.

When your doctor stops treatment with Voriconazol Accord, you should not experience any effects from stopping treatment.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

If any appear, it is most likely to be mild and transient. However, some may be serious and require medical attention.

Severe Adverse Effects - Stop taking Voriconazol Accord and see a doctor immediately

immediately

• Skin rash.
• Jaundice; changes in liver function detected in blood tests.
• Pancreatitis.

Other Adverse Effects

Very common: may affect more than 1 in 10 people

Visual disturbance (change in vision, such as blurred vision, visual disturbances of colors, abnormal intolerance to visual perception of light, color blindness, eye disorder, visual alopecia, night blindness, oscillating vision, spark vision, visual aura, decreased visual acuity, visual clarity, partial loss of usual visual field, spots in the visual field).

• Fever.
• Skin rash.
• Nausea, vomiting, and diarrhea.
• Headache.
• Swelling of the limbs.
• Stomach pain.
• Difficulty breathing.
• Elevated liver enzymes.

Common: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low count, including severe, of some types of red blood cells (sometimes of an immune nature) and/or white blood cells (sometimes accompanied by fever) in the blood, low platelet count that helps blood clot.
• Low blood sugar levels, low potassium levels in the blood, low sodium levels in the blood.
• Anxiety, depression, confusion, agitation, insomnia, hallucinations.
• Seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, somnolence, dizziness.
• Ocular hemorrhage.
• Heart rhythm problems, including very fast heartbeat, very slow heartbeat, fainting, hypotension, vein inflammation (which may be associated with blood clot formation).
• Acute difficulty breathing, chest pain, swelling of the face (mouth, lips, and around the eyes), fluid retention in the lungs.
• Constipation, indigestion, lip inflammation.
• Jaundice (yellowish skin color), liver inflammation, and liver damage.
• Skin eruptions, which can be severe, with blisters and peeling, characterized by a flat and reddened area, covered with small bumps that converge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, blood in urine, alterations in blood tests to control kidney function.

Uncommon: may affect up to 1 in 100 people

• Flu-like symptoms, irritation, and inflammation of the gastrointestinal tract, inflammation of the gastrointestinal tract that causes antibiotic-associated diarrhea, inflammation of the lymphatic vessels.
• Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal organs.
• Enlargement (sometimes painful) of the lymph nodes, bone marrow failure, increased eosinophils.

• Decreased adrenal gland function, underactive thyroid gland.
• Abnormal brain function, symptoms similar to Parkinson's disease, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Problems with balance or coordination.
• Brain swelling.
• Double vision, serious eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage that causes vision changes, inflammation of the optic papilla.

• Decreased sensitivity to touch.
• Alteration of the sense of taste.
• Difficulty hearing, ringing in the ears, vertigo.
• Inflammation of certain internal organs, pancreas, and duodenum, swelling, and inflammation of the tongue.
• Enlargement of the liver, hepatitis, liver failure, gallbladder disease, gallstones.
• Joint inflammation, vein inflammation under the skin (which may be associated with blood clot formation).
• Kidney inflammation, protein in the urine, kidney damage.
• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• High cholesterol in the blood, high urea in the blood.

Allergic skin reactions (sometimes severe), such as a potentially life-threatening skin disease that causes painful blisters and ulcers on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, sunburn, or severe skin reaction after exposure to light or sun, skin redness and irritation, reddish or purplish skin color that may be caused by low platelet count, eczema.

• Infusion site reaction.
• Allergic reaction or exaggerated immune response.

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

• Overactive thyroid gland.
• Worsening of brain activity as a serious complication of liver disease.

• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movement.
• Blisters due to photosensitivity.
• Disorder in which the immune system attacks part of the peripheral nervous system.
• Heart rhythm or conduction problems (sometimes potentially life-threatening).
• Potentially life-threatening allergic reaction.
• Alterations in blood coagulation.
• Allergic skin reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with silvery scales, skin irritation, and mucous membrane irritation, potentially life-threatening skin disease that causes large portions of the epidermis, the outermost layer of skin, to peel off from the underlying skin layers.
• Small, scaly, and dry skin patches, sometimes thick and with tips or "horns".

Adverse effects with unknown frequency:

• Pigmented spots and patches.

Other important adverse effects whose frequency is not known, but which should be reported to the doctor immediately:

• Skin cancer.
• Inflammation of the tissue surrounding the bone.
• Red, scaly skin patches or ring-shaped lesions that may be a symptom of an autoimmune disease called cutaneous lupus erythematosus.

Since Voriconazol Accord has been observed to affect the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. Warn your doctor if you have stomach pain or if your stools have a different consistency.

Cases of skin cancer have been reported in patients treated with Voriconazol Accord for long periods.

The frequency of sunburn or severe skin reactions after exposure to light or sun was higher in children. If you or your child have skin disorders, your doctor may refer you to a dermatologist who, after consultation, may decide that it is important for you or your child to undergo regular follow-up. Elevated liver enzymes were also observed more frequently in children.

If any of these adverse effects persist or are bothersome, report them to your doctor.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Voriconazol Accord

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

Do not use this medicine after the expiration date that appears on the label. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Voriconazol Accord Composition

• The active ingredient is voriconazole. Each tablet contains 50 mg of voriconazole (for Voriconazol Accord 50 mg film-coated tablets) or 200 mg of voriconazole (for Voriconazol Accord 200 mg film-coated tablets).
• The other ingredients are lactose monohydrate, pregelatinized starch, sodium croscarmellose, povidone, and magnesium stearate, which make up the tablet core, and hypromellose, titanium dioxide (E171), lactose monohydrate, and triacetin, which make up the film coating.

Product Appearance and Package Contents

Voriconazol Accord 50 mg tablets are presented as film-coated tablets, white to off-white in color, and round in shape, approximately 7.0 mm in diameter, with "V50" engraved on one side and smooth on the other.

Voriconazol Accord 200 mg tablets are presented as film-coated tablets, white to off-white in color, and oval in shape, approximately 15.6 mm long and 7.8 mm wide, with "V200" engraved on one side and smooth on the other.

Voriconazol Accord 50 mg film-coated tablets and Voriconazol Accord 200 mg film-coated tablets are available in packs of 2, 10, 14, 20, 28, 30, 50, 56, and 100 or monodose blister packs (PVC/aluminum) containing 10x1, 14x1, 28x1, 30x1, 56x1, or 100x1 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona,

Spain

Manufacturer

Accord Healthcare Limited,

Sage House, 319 Pinner Road,

North Harrow,

Middlesex, HA1 4HF,

United Kingdom

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park,

Paola, PLA 3000

Malta

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

This prospectus was approved on {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency website http://www.ema.europa.eu.