Voriconazole Kern Pharma 200 mg powder for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Voriconazole Kern Pharma 200 mg powder for solution for infusion EFG

Read all of this leaflet carefully before you start using 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 or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It could harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Voriconazole Kern Pharma is and what it is used for
2. What you need to know before using Voriconazole Kern Pharma
3. How to use Voriconazole Kern Pharma
4. Possible side effects
5. How to store Voriconazole Kern Pharma
6. Contents of the pack and other information

1. What Voriconazol Kern Pharma is and what it is used for

Voriconazol Kern Pharma contains the active substance voriconazole. Voriconazole is an antifungal medicine. It works by killing or preventing 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 spp),
• candidaemia (another type of fungal infection caused by Candida spp) in non-neutropenic patients (patients who do not have an abnormally low white blood cell count),
• serious invasive infections caused by Candida spp, when the fungus is resistant to fluconazole (another antifungal medicine),
• serious fungal infections caused by Scedosporium spp or Fusarium spp (two different species of fungi).

Voriconazol Kern Pharma is used in patients with serious fungal infections that may be life-threatening.

Prevention of fungal infections in bone marrow transplant recipients at high risk.

This medicine should only be used under medical supervision.

2. What you need to know before starting to use Voriconazole Kern Pharma

Do not use Voriconazole Kern Pharma

• 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 obtained without a prescription, or herbal remedies.

During treatment with voriconazole, 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 heart arrhythmias).
• 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, herbal remedy).

Warnings and precautions

Talk to your doctor before starting voriconazole if:

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

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

While being treated with voriconazole, inform your doctor if you experience:

• sunburn,
• severe skin rash or blistering,
• bone pain.

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

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

Children and adolescents

This medicine should not be administered to children under 2 years of age.

Using Voriconazole Kern Pharma with other medicines

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

• Some medicines, when used at the same time as Voriconazole Kern Pharma, may affect the action of voriconazole, or voriconazole may affect the action of other medicines.

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

• Ritonavir (used to treat HIV) at a dose of 100 mg twice daily.

Inform your doctor if you are taking any of the following medicines, as concomitant treatment with voriconazole should be avoided if possible, and 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 should be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, the concentration of phenytoin in your blood should be monitored during treatment with voriconazole, and your dose may need to be adjusted.

Tell your doctor if you are taking any of the following medicines, as dose adjustment or monitoring may be needed to ensure these medicines and/or voriconazole 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 use voriconazole while taking oral contraceptives, you may experience adverse effects such as nausea and menstrual disorders).
• Vinca alkaloids (e.g.: vincristine, 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, nevirapine) (used to treat HIV infection) (some doses of efavirenz CANNOT be taken with voriconazole).
• 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).
• Flucloxacillin (an antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding

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

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

Driving and using machines

This medicine 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.

Voriconazole Kern Pharma contains sodium

Patients on low-sodium diets should be aware that this medicine contains 88.74 mg (3.86 mmol) of sodium per vial.

3. How to use Voriconazol Kern Pharma

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, consult your doctor or pharmacist again.

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

Your doctor may adjust the dose according to your condition.

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

Depending on your response to treatment, your doctor may reduce the dose to 3 mg/kg twice daily.

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.

Voriconazole powder for solution for infusion must be reconstituted and diluted to the correct concentration by hospital pharmacy or nursing staff (for more information, see the end of this leaflet).

It will be administered by intravenous infusion (into a vein) at a maximum rate of 3 mg/kg per hour for 1 to 3 hours.

If you or your child are taking voriconazole to prevent fungal infections, your doctor may discontinue voriconazole treatment if you or your child experience adverse effects related to the treatment.

If you forget to use Voriconazol Kern Pharma

Since you will be receiving this medicine under close medical supervision, it is unlikely that you will miss a dose. However, inform your doctor or pharmacist if you think a dose has been missed.

If you stop treatment with Voriconazol Kern Pharma

Voriconazole treatment should be maintained for as long as your doctor considers appropriate; however, the duration of treatment with voriconazole powder for solution for infusion should not exceed 6 months.

Patients with weakened immune systems or those with complicated infections may require longer treatment courses to prevent the infection from recurring. Once your condition improves, intravenous infusion may be switched to oral tablets.

When your doctor discontinues voriconazole treatment, 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 or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. If they occur, they are most likely to be mild and temporary. However, some may be serious and require immediate medical attention.

Serious adverse effects – Stop using this medicine and contact your doctor immediately

• Skin rash.
• Jaundice, changes in blood tests monitoring 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 halos, night blindness, oscillating vision, seeing sparks, visual aura, decreased visual acuity, reduced clarity of vision, partial loss of the usual visual field, spots in the visual field).
• Fever.
• Skin rash.
• Nausea, vomiting, and diarrhea.
• Headache.
• Swelling of the extremities.
• Stomach pain.
• Difficulty breathing.
• Elevated liver enzymes.

Common (may affect up to 1 in 10 people):

• Sinusitis, gum inflammation, chills, weakness.
• Low blood count, 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.
• Allergic reaction or exaggerated immune response.
• Low blood sugar, low blood potassium, low blood sodium.
• Anxiety, depression, confusion, agitation, insomnia, hallucinations.
• Seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, drowsiness, dizziness.
• Ocular 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 difficulty breathing, chest pain, facial swelling (mouth, lips, and around the eyes), fluid accumulation in the lungs.
• Constipation, indigestion, lip inflammation.
• 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 blood tests monitoring kidney function.

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 the lymphatic vessels.
• Inflammation of the thin tissue lining the abdominal wall and covering the abdominal organs (peritonitis).
• Enlargement (sometimes painful) of lymph nodes, bone marrow failure, increased eosinophils.
• Reduced adrenal gland function, underactive thyroid gland.
• Abnormal brain function, Parkinson-like symptoms, nerve damage causing numbness, pain, tingling, or burning sensations in hands or feet.
• Coordination problems.
• Brain swelling.
• Double vision, serious eye disorders 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 in taste sensation.
• Hearing difficulty, ringing in the ears, vertigo.
• Inflammation of certain internal organs, pancreas and duodenum, swelling and inflammation of the tongue.
• Enlarged liver, 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 potentially life-threatening skin disease causing blisters and painful sores 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 discoloration possibly caused by low platelet count, eczema.
• Reaction at the infusion site.

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, irritation of the skin and mucous membranes, potentially life-threatening skin disease causing large portions of the epidermis, the outermost skin 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:

• Skin cancer.
• Inflammation of the tissue surrounding the bone.
• Scaly red patches or ring-shaped skin lesions, which may be symptoms of an autoimmune disease called cutaneous lupus erythematosus.

During infusion, infrequently, reactions with voriconazole have occurred (including facial flushing, fever, sweating, increased heart rate, and difficulty breathing). Your doctor may stop the infusion if this happens.

Since voriconazole 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 have stomach pain or if your stools have an unusual consistency.

Cases of skin cancer have been reported in patients treated with voriconazole over long periods.

The frequency of sunburns or severe skin reactions following exposure to light or sun 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 monitoring 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 or pharmacist, even if it is an effect not listed in this leaflet. You can 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 Voriconazole Kern Pharma

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

Do not use this medicine after the expiry date stated on the container, following "EXP". The expiry date refers to the last day of the month indicated.

After reconstitution, this medicine must be used immediately; however, if necessary, it may be stored for up to 24 hours between 2°C and 8°C (in a refrigerator). Reconstituted Voriconazole Kern Pharma must first be diluted with a compatible perfusion diluent before being administered by infusion. (For further information, see the end of this leaflet.)

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

6. Package contents and other information

Composition of VoriconazolKern Pharma

• The active substance is voriconazol.
• The other components are hydroxypropyl-beta-cyclodextrin, sodium chloride, and hydrochloric acid.

Each vial contains 200 mg of voriconazol, equivalent to a 10 mg/ml concentrated solution once reconstituted according to the instructions provided by hospital pharmacy or nursing staff (see information at the end of this leaflet).

Appearance of the product and contents of the pack

Voriconazol Kern Pharma is presented as a powder for infusion solution in single-use 25 ml glass vials (type I), fitted with a rubber stopper and an aluminum seal with a plastic cap.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Manufacturer

Anfarm Hellas S.A.

Schimatari Viotias

320 09

Greece

or

Pharmathen S.A.

Dervenakion 6

15351 Pallini

Attikis - Greece

or

Pharmathen International S.A.

Sapes Industrial Park, Block 5

69300 Rodopi - Greece

Date of the most recent revision of this leaflet: June 2023.

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Reconstitution and dilution instructions

• Voriconazol Kern Pharma powder for infusion solution must be reconstituted with 19 ml of water for injections or 19 ml of sodium chloride 9 mg/ml (0.9%) for infusion to obtain a 20 ml extractable volume of clear concentrate containing 10 mg/ml of voriconazol.
• Discard the Voriconazol Kern Pharma vial if the vacuum does not allow the solvent to be introduced into the vial.
• A standard 20 ml syringe (non-automatic) is recommended to ensure the exact amount (19.0 ml) of water for injections or sodium chloride 9 mg/ml (0.9%) is dispensed.
• The required volume of reconstituted concentrate is then added to a compatible infusion solution listed below, to produce a final Voriconazol Kern Pharma solution containing 0.5 to 5 mg/ml of voriconazol.
• This medicinal product is for single use only, and any unused solution must be discarded. Only use clear solutions free from particles.
• Must not be administered as an intravenous bolus.
• For storage information, see section 5 “Storage of Voriconazol Kern Pharma”.

Required volumes of Voriconazol Kern Pharma concentrate 10 mg/ml

Voriconazole Kern Pharma is a sterile, single-dose lyophilisate without preservatives. Therefore, from a microbiological standpoint, the solution should be used immediately after reconstitution. If not used immediately, the time and conditions of storage prior to use are the responsibility of the user and must be maintained between 2 and 8°C (in the refrigerator) for a maximum of 24 hours, unless reconstitution has been carried out under controlled, validated aseptic conditions.

Compatible infusion solutions:

The reconstituted solution may be diluted with:

• Sodium chloride 9 mg/mL (0.9%) injection solution.
• Sodium lactate compound intravenous infusion.
• 5% glucose and Ringer's lactate solution for intravenous infusion.
• 5% glucose and 0.45% sodium chloride solution for intravenous infusion.
• 5% glucose solution for intravenous infusion.
• 5% glucose with 20 mEq potassium chloride solution for intravenous infusion.
• 0.45% sodium chloride solution for intravenous infusion.
• 5% glucose and 0.9% sodium chloride solution for intravenous infusion.

The compatibility of voriconazole with diluents other than those specifically listed above (or those mentioned below under "Incompatibilities") is unknown.

Incompatibilities:

Voriconazole Kern Pharma must not be infused simultaneously through the same line or cannula with other drug infusions, including parenteral nutrition (e.g., Aminofusin 10% Plus).

Concomitant infusions of blood products must not be administered during administration of Voriconazole Kern Pharma.

Total parenteral nutrition may be administered simultaneously with Voriconazole Kern Pharma, but not through the same line or cannula.

Voriconazole Kern Pharma must not be diluted with 4.2% sodium bicarbonate solution.