Vfend 40 mg/ml powder for oral suspension

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

VFEND 40 mg/ml powder for oral suspension

voriconazole

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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 and you should not give it to other people, even if they have the same symptoms as you, since it could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What VFEND is and what it is used for

VFEND contains the active substance voriconazole. VFEND is an antifungal medicine. It works by killing or stopping the growth of fungi that cause infections.

It is used to treat patients (adults and children aged 2 years and older) with:

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

VFEND is used in patients with serious fungal infections that may be life-threatening.

Prevention of fungal infections in haematopoietic stem cell transplant recipients at high risk.

This medicine should only be used under medical supervision.

2. What you need to know before starting VFEND

Do not take VFEND:

if you are allergic to voriconazole or to any of the other components of this medicine (listed in section 6).

It is very important that you inform your doctor or pharmacist if you are currently using, have recently used, or might need to take any other medicines or herbal products.

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

• Terfenadine (used for allergies).
• Astemizole (used for allergies).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for cardiac arrhythmias).
• Ivabradine (used for symptoms of chronic heart failure).
• Rifampicin (used to treat tuberculosis).
• Efavirenz (used to treat HIV) at doses of 400 mg or higher 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 transplant patients).
• Ritonavir (used to treat HIV) at doses of 400 mg or higher twice daily.
• St. John’s wort (Hypericum perforatum, herbal remedy).
• Naloxegol (used to treat constipation specifically caused by painkillers called opioids [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat hyponatremia [low sodium levels in blood] or to slow down 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 leukemia [CLL]).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting VFEND if:

• you have had an allergic reaction to other azole antifungals.
• you currently have or have ever had liver disease. If you have liver disease, your doctor may prescribe a lower dose of VFEND. Your doctor should also monitor your liver function during treatment with VFEND by performing blood tests.
• you know you have cardiomyopathy, irregular heartbeat, slow heart rate, or an abnormality on the electrocardiogram (ECG) known as “prolonged QTc syndrome”.

You must avoid exposure to sunlight and UV light during treatment. It is important to cover exposed areas and use sunscreen with a high sun protection factor (SPF), as your skin may become more sensitive to UV radiation from sunlight. This sensitivity may be further increased by other medicines that make the skin sensitive to sunlight, such as methotrexate. These precautions also apply to children.

While you are being treated with VFEND:

• inform your doctor if you develop

• sunburn

• severe skin rash or blistering

• bone pain

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who may consider regular monitoring necessary. There is a small possibility of developing skin cancer with long-term use of VFEND.

If you develop signs of “adrenal insufficiency”, in which the adrenal glands do not produce sufficient amounts of certain steroid hormones such as cortisol, which may cause symptoms such as: prolonged or chronic 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 too much cortisol hormone, which may cause symptoms such as: weight gain, fatty hump between the shoulders, rounded face, darkening of the skin on the abdomen, thighs, breasts, and arms, thin skin, easy bruising, high blood sugar levels, excessive hair growth, or excessive sweating, inform your doctor.

Your doctor should monitor the function of your liver and kidneys through blood tests.

Children and adolescents

VFEND must not be given to children under 2 years of age.

Other medicines and VFEND

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicine.

Some medicines, when taken at the same time as VFEND, may affect the action of VFEND or VFEND may affect the action of other medicines.

Inform your doctor if you are taking the following medicines, as concomitant treatment with VFEND should be avoided if possible:

• Ritonavir (used to treat HIV) at a dose of 100 mg twice daily.
• Glasdegib (used to treat cancer); if you need to take both medicines, your doctor will frequently monitor your heart rhythm.

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

• Rifabutin (used to treat tuberculosis). If you are already being treated with rifabutin, your blood count and adverse effects of rifabutin will need to be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, the concentration of phenytoin in your blood will need to be monitored during treatment with VFEND, 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 ensure these medicines and/or VFEND remain effective:

• Warfarin and other anticoagulants (e.g.: phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Cyclosporine (used in transplant patients).
• Tacrolimus (used in transplant patients).
• Sulfonylureas (e.g.: tolbutamide, glipizide, glyburide) (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 to treat stomach ulcers).
• Oral contraceptives (if you take VFEND while using oral contraceptives, you may experience adverse effects such as nausea and menstrual disorders).
• Vinca alkaloids (e.g.: vincristine, 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).
• 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) (some doses of efavirenz cannot be taken with VFEND).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids such as sufentanil (analgesics used during surgery).
• Oxycodone and other long-acting opioids 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 renal cell carcinoma and in transplant patients).
• Letermovir (used to prevent cytomegalovirus (CMV) infection after bone marrow transplant).
• Ivacaftor: used to treat cystic fibrosis.
• Flucloxacillin (an antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding

Do not take VFEND during pregnancy unless specifically instructed by your doctor. Women of childbearing potential being treated with VFEND should use effective contraception. Contact your doctor immediately if you become pregnant while taking VFEND.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

VFEND may cause blurred vision or discomfort due to increased sensitivity to light. If this occurs, do not drive or operate tools or machinery, and inform your doctor.

VFEND contains sucrose

This medicine contains sucrose. If your doctor has told you that you have an intolerance to certain sugars, consult him or her before taking this medicine.

Patients with diabetes mellitus should be aware that this medicine contains 0.54 g of sucrose per ml of suspension.

It may cause dental caries.

VFEND contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 5 ml of suspension; hence, it is essentially “sodium-free”.

VFEND contains benzoic acid/sodium salt

This medicine contains 12 mg of benzoic acid sodium salt (E211) in each 5 ml dose.

3. How to take VFEND

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

Your doctor will determine the dose based on your body 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 7.5 ml (300 mg) twice a day.

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

Use in children and adolescents

The recommended dose in children and adolescents is as follows:

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

Take the suspension at least one hour before or two hours after a meal.

If you or your child are taking VFEND for prevention of fungal infections, your doctor may discontinue treatment with VFEND if you or your child experience adverse effects related to the treatment.

VFEND suspension must not be mixed with any other medicine. The suspension must not be further diluted with water or other liquids.

Instructions for preparing the suspension

It is recommended that your pharmacist prepare the VFEND suspension before giving it to you.

VFEND suspension is reconstituted when in liquid form. If it appears as dry powder, the oral suspension must be reconstituted following the instructions detailed below:

1. Tap the bottle gently to loosen the powder.

2. Remove the cap.

3. Add 2 dosing cups (the dosing cup is included in the package) of water (up to a total of 46 ml) to the bottle. Fill the dosing cup up to the top of the marked line, then add the measured water to the bottle. A total of 46 ml of water must always be added, regardless of the dose you are to take.

4. Replace the cap and shake the bottle vigorously for approximately 1 minute. After reconstitution, the total volume of the suspension should be 75 ml.

5. Remove the cap. Press the adapter firmly into the neck of the bottle (as shown in the following illustration). The adapter is provided to allow the oral syringe to be filled with the medicine from the bottle. Replace the cap on the bottle.

6. Record the expiration date of the reconstituted suspension on the label of the bottle (the reconstituted suspension is valid for 14 days). Any remaining suspension must be discarded after this date.

Instructions for use:

Your pharmacist should explain to you how to measure the medicine using the multi-dose oral syringe provided in the package. Please read the following instructions before using VFEND suspension.

1. Shake the closed bottle containing the reconstituted suspension for approximately 10 seconds before use. Remove the cap.
2. With the bottle upright and placed on a flat surface, insert the tip of the oral syringe into the adapter.
3. Keeping the syringe in place, turn the bottle upside down. Slowly pull the syringe plunger to the graduation mark corresponding to your dose.
4. If large air bubbles are visible, slowly press the syringe plunger. This will return the medicine back into the bottle. Repeat step 3 again.
5. Place the bottle upright with the syringe still in place. Remove the syringe from the bottle.
6. Place the tip of the syringe into the mouth. Direct the syringe toward the inside of the cheek. Press the syringe plunger SLOWLY. Do not expel the medicine rapidly. If administering the medicine to a child, ensure the child is sitting or held upright before giving the medicine.
7. Replace the cap on the bottle, leaving the adapter in place. Wash the syringe following the instructions below.

Cleaning and storage of the syringe:

1. The syringe must be washed after each use. Remove the plunger from the syringe and wash both parts with lukewarm soapy water. Then rinse with water.
2. Dry both parts. Replace the plunger into the syringe. Store in a clean and safe place together with the medicine.

If you take more VFEND than you should

If you take more suspension than prescribed (or if someone else takes your suspension), seek immediate medical help or go to the nearest hospital emergency department. Take your bottle of VFEND suspension with you. You may experience abnormal sensitivity to light as a result of taking more VFEND than you should.

If you forget to take VFEND

It is important to take VFEND suspension regularly at the same time each day. 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 VFEND

It has been shown that correctly following the prescribed dosing schedule, by taking each dose at the appropriate time, can significantly increase the effectiveness of this medicine. Therefore, unless your doctor tells you otherwise, it is important that you continue taking VFEND correctly as described above.

Continue taking VFEND until your doctor tells you otherwise. Do not stop treatment prematurely, as the infection may not be cured. Patients with compromised immune systems or with complicated infections may require longer treatment to prevent the infection from recurring.

When your doctor discontinues treatment with VFEND, you should not experience any effects due to stopping the treatment.

If you have any further questions about 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 everyone will experience them.

If any occur, they are most likely to be mild and transient. However, some may be serious and require immediate medical attention.

Serious adverse effects – Stop taking VFEND and contact your doctor immediately

• Skin rash.
• Jaundice, changes in blood tests assessing liver function.
• Pancreatitis.

Other adverse effects

Very common: may affect more than 1 in 10 people

• Visual disturbance (changes in vision, such as blurred vision, disturbances in color vision, abnormal intolerance to visual perception of light, color blindness, eye disorder, visual halo, night blindness, oscillating vision, perception of sparks, visual aura, decreased visual acuity, reduced visual clarity, partial loss of normal 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 blood counts, including severe cases, of certain types of red blood cells (sometimes immune-mediated) or white blood cells (sometimes accompanied by fever), low platelet count affecting blood clotting.
• Low blood sugar levels, low blood potassium levels, low blood sodium levels.
• Anxiety, depression, confusion, agitation, insomnia, hallucinations.
• Seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, drowsiness, dizziness.
• Eye hemorrhage.
• Heart rhythm problems, including very fast heartbeat, very slow heartbeat, fainting.
• Hypotension, inflammation of veins (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, lip swelling.
• Jaundice (yellowing of the skin), liver inflammation, and liver damage.
• Skin rashes, which may become severe, with blisters and peeling, characterized by flat, red areas covered with small merging bumps, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, presence of blood in urine, abnormalities in tests assessing kidney function.
• Sunburn or severe skin reaction after exposure to light or sunlight.
• 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 diarrhea, inflammation of lymphatic vessels.
• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs.
• Enlargement (sometimes painful) of lymph nodes, bone marrow failure, increased eosinophils.
• Reduced adrenal gland function, underactive thyroid gland.
• Abnormal brain function, symptoms resembling Parkinson's disease, nerve damage causing numbness, pain, tingling, or burning sensations in 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 causing vision disturbances, optic disc inflammation.
• Reduced sensitivity to touch.
• Disturbance of taste sensation.
• Hearing difficulty, ringing in the ears, vertigo.
• Inflammation of certain internal organs, pancreas and duodenum, swelling and inflammation of the tongue.
• Liver enlargement, liver failure, gallbladder disease, gallstones.
• Joint inflammation, inflammation of veins under the skin (which may be associated with blood clot formation).
• Kidney inflammation, protein in urine, kidney damage.
• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.
• Skin allergic reactions (sometimes severe), such as skin disease, potentially life-threatening causing blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness and irritation, reddish or purplish skin discoloration possibly caused by low platelet count, eczema.
• Reaction at the infusion site.
• Allergic reaction or exaggerated immune response.
• Inflammation of tissue surrounding the bone.

Rare: may affect 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 fibers, 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 or conduction problems (sometimes potentially fatal).
• Potentially life-threatening allergic reaction.
• Blood clotting disorders.
• Skin allergic reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, itchy and painful thickened red skin plaques with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin disease causing large sections of the epidermis, the skin's outermost layer, to detach from underlying skin layers.
• Small scaly, dry skin patches, sometimes thick with tips or "horns".

Adverse effects with unknown frequency:

• Freckles and pigmented spots.

Other important adverse effects with unknown frequency, but which must be reported to your doctor immediately:

• Scaly red patches or ring-shaped skin lesions, which may be a symptom of an autoimmune disease called cutaneous lupus erythematosus.

Since VFEND has been observed to affect the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. 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 VFEND for long periods.

The frequency of sunburns or severe skin reactions after exposure to light or sunlight was higher in children. If you or your child develop skin disorders, your doctor may refer you to a dermatologist who, after evaluation, may decide that regular follow-up is necessary. Elevated liver enzymes were also observed more frequently in children.

If any of these adverse effects persist or are bothersome, inform your doctor.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of VFEND

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

Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the month indicated.

Oral suspension powder: store between 2 °C and 8 °C (in the refrigerator) prior to reconstitution.

For the suspension, after reconstitution:

Do not store at temperatures above 30 °C.

Do not store in the refrigerator or freeze.

Keep in the original container.

Keep the container tightly closed.

Any unused portion of the suspension must be discarded 14 days after reconstitution.

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

6. Contents of the pack and other information

Composition of VFEND

• The active substance is voriconazole. Each vial contains 45 g of powder, which when reconstituted with water according to the instructions yields 70 ml of suspension. One ml of the reconstituted suspension contains 40 mg of voriconazole. (see section 3 'How to take VFEND')
• The other components are sucrose; colloidal silicon dioxide; titanium dioxide; xanthan gum; sodium citrate; sodium benzoate; citric acid; natural orange flavour (see section 2, VFEND 40 mg/ml powder for oral suspension contains sucrose, benzoic acid salt (sodium benzoate) and sodium).

Appearance of the product and contents of the pack

VFEND is presented as a white to off-white powder for oral suspension which, when reconstituted with water, forms a white to off-white suspension with an orange flavour.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:
Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

Manufacturer:
Fareva Amboise, Zone Industrielle, 29 route des Industries, 37530 Pocé-sur-Cisse, France.

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder.

Date of the most recent approval of this package leaflet: 04/2024.

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