Voriconazole Fresenius Kabi

Package Leaflet: Information for the User

Voriconazole Fresenius Kabi, 200 mg, Powder for Solution for Infusion

Voriconazole

Read All of This Leaflet Carefully Before You Start Using This Medicine.

• Keep This Leaflet. You May Need to Read It Again.
• If You Have Any Further Questions, Ask Your Doctor, Pharmacist, or Nurse.
• If You Get Any Side Effects, Talk to Your Doctor, Pharmacist, or Nurse. This Includes Any Possible Side Effects Not Listed in This Leaflet. See Section 4.

Contents of the Pack

• 1. What Voriconazole Fresenius Kabi Is and What It Is Used For
• 2. Before You Use Voriconazole Fresenius Kabi
• 3. How to Use Voriconazole Fresenius Kabi
• 4. Possible Side Effects
• 5. How to Store Voriconazole Fresenius Kabi
• 6. Contents of the Pack and Other Information

1. What Voriconazole Fresenius Kabi Is and What It Is Used For

Voriconazole Fresenius Kabi Contains the Active Substance Voriconazole. Voriconazole Fresenius Kabi Is an Antifungal Medicine. It Works by Killing Fungi That Cause Infections or Stopping Them from Growing.

This Medicine Is Used to Treat Patients (Adults and Children from 2 Years of Age) with:

• Invasive Aspergillosis (a Type of Fungal Infection Caused by Fungi of the Genus Aspergillus);
• Candidemia (Another Type of Fungal Infection Caused by Fungi of the Genus Candida) in Patients Without Neutropenia (Those Who Do Not Have a Decreased Number of White Blood Cells);
• Severe Invasive Candida Infections Resistant to Fluconazole (Another Antifungal Medicine);
• Severe Fungal Infections Caused by Fungi of the Genus Scedosporiumand Fusarium(Two Different Types of Fungi).

Voriconazole Fresenius Kabi Is Intended for Use in Patients with Progressive, Life-Threatening Fungal Infections.

This Medicine Is Used to Prevent Fungal Infections in Patients at High Risk After Bone Marrow Transplantation.

This Medicine Should Only Be Used Under the Supervision of a Doctor.

2. Before You Use Voriconazole Fresenius Kabi

Do Not Use Voriconazole Fresenius Kabi:

• If You Are Allergic to Voriconazole or Any of the Other Ingredients of This Medicine (Listed in Section 6). It Is Very Important to Inform Your Doctor or Pharmacist About All Medicines You Are Currently Taking or Have Recently Taken, Even Those That Are Available Without a Prescription or Herbal Medicines.

Do Not Use Voriconazole Fresenius Kabi at the Same Time as Any of the Following Medicines:

• Terfenadine (Used to Treat Allergies);
• Astemizole (Used to Treat Allergies);
• Cisapride (Used to Treat Stomach Disorders);
• Pimozide (Used to Treat Mental Illnesses);
• Quinidine (Used to Treat Heart Rhythm Disorders);
• Ivabradine (Used to Treat Symptoms of Chronic Heart Failure);
• Rifampicin (Used to Treat Tuberculosis);
• Efavirenz (Used to Treat HIV Infection) at Doses of 400 Mg and Higher, Taken Once a Day;
• Carbamazepine (Used to Treat Epilepsy);
• Phenobarbital (Used to Treat Severe Insomnia and Epilepsy);
• Ergot Alkaloids (e.g., Ergotamine, Dihydroergotamine, Used to Treat Migraines);
• Sirolimus (Used in Patients After Organ Transplantation);
• Ritonavir (Used to Treat HIV Infection) at Doses of 400 Mg and Higher, Taken Twice a Day;
• St. John's Wort (Hypericum Perforatum L.) (Herbal Medicine);
• Naloxegol [Used to Treat Constipation Caused by Opioid Painkillers (e.g., Morphine, Oxycodone, Fentanyl, Tramadol, Codeine)];
• Tolvaptan [Used to Treat Hyponatremia (a Condition of Low Sodium Levels in the Blood) or to Slow the Worsening of Kidney Function in Patients with Polycystic Kidney Disease];
• Luraxadone (Used to Treat Depression);
• Venetoclax [Used to Treat Patients with Chronic Lymphocytic Leukemia (CLL)].

Warnings and Precautions

Before You Start Using Voriconazole Fresenius Kabi, Discuss with Your Doctor, Pharmacist, or Nurse If:

• You Have Had an Allergic Reaction to Other Azoles in the Past;
• You Have or Have Had Liver Disease. Your Doctor May Prescribe a Lower Dose of Voriconazole Fresenius Kabi If You Have Liver Disease. Your Doctor Should Also Monitor Your Liver Function During Treatment with Voriconazole Fresenius Kabi;
• You Have Been Diagnosed with Cardiomyopathy, Heart Rhythm Disorders, Slow Heartbeat, or Changes in the Electrocardiogram (ECG) Called "Prolonged QTc Interval".

Avoid Any Exposure to Sunlight and Sun During Treatment.

It Is Important to Cover Areas of Skin Exposed to Sunlight and Use Sunscreens with a High Protection Factor (SPF) Because Photosensitivity Reactions (UV) May Occur. These Precautions Also Apply to Children.

Tell Your Doctor Immediately If You Experience:

• Sunburn;
• Severe Rash or Blisters on the Skin;
• Bone Pain.

If Skin Disorders Occur, Your Doctor May Refer You to a Dermatologist, Who May Decide on the Need for Regular Visits. There Is a Small Risk That Long-Term Use of Voriconazole Fresenius Kabi May Cause Skin Cancer.

Tell Your Doctor If You Experience Symptoms of "Adrenal Insufficiency", a Condition in Which the Adrenal Glands Do Not Produce Enough of Certain Steroid Hormones, Such as Cortisol. These Symptoms Include: Chronic or Long-Term Fatigue, Muscle Weakness, Loss of Appetite, Weight Loss, Abdominal Pain.

Tell Your Doctor If You Experience Symptoms of "Cushing's Syndrome", a Condition in Which the Body Produces Too Much of the Hormone Cortisol, Which Can Lead to Symptoms Such as Weight Gain, Appearance of a Hump of Fat Between the Shoulder Blades, Rounded Face, Darkening of the Skin on the Abdomen, Thighs, Chest, and Arms, Thinning of the Skin, Increased Bruising, High Blood Sugar, Excessive Hair Growth, Excessive Sweating.

Your Doctor Should Monitor Your Liver and Kidney Function with Appropriate Blood Tests.

Children and Adolescents

Voriconazole Fresenius Kabi Should Not Be Used in Children Under 2 Years of Age.

Voriconazole Fresenius Kabi and Other Medicines

Tell Your Doctor or Pharmacist About All Medicines You Are Currently Taking or Plan to Take, Including Those Available Without a Prescription.

Some Medicines Used at the Same Time as Voriconazole Fresenius Kabi May Change Its Effect, and Voriconazole Fresenius Kabi May Affect the Action of Other Medicines.

Tell Your Doctor About the Use of the Following Medicines, as Their Concurrent Use with Voriconazole Fresenius Kabi Should Be Avoided If Possible:

• Ritonavir (Used to Treat HIV Infection) at a Dose of 100 Mg, Taken Twice a Day.
• Glasdegib (Used to Treat Cancer) - If Both Medicines Need to Be Used, Your Doctor Will Order Frequent Monitoring of Heart Rhythm.

Tell Your Doctor About the Use of Any of the Following Medicines, as Their Concurrent Use with Voriconazole Fresenius Kabi Should Be Avoided If Possible, and If Not, the Dose of Voriconazole May Need to Be Adjusted:

• Rifabutin (Used to Treat Tuberculosis). If You Are Being Treated with Rifabutin, Your Doctor Will Monitor Your Blood Parameters and Rifabutin Side Effects.
• Phenytoin (Used to Treat Epilepsy). If You Are Being Treated with Phenytoin While Taking Voriconazole Fresenius Kabi, Your Doctor Will Monitor Its Blood Levels and May Need to Adjust the Dose.

If You Are Taking Any of the Following Medicines, Tell Your Doctor, as Their Dose May Need to Be Adjusted or Monitored to Ensure That These Medicines and Voriconazole Fresenius Kabi Continue to Work as Expected:

• Warfarin and Other Anticoagulants (e.g., Phenprocoumon, Acenocoumarol; Used to Reduce Blood Clotting);
• Cyclosporine (Used After Organ Transplantation);
• Tacrolimus (Used After Organ Transplantation);
• Sulfonylurea Derivatives (e.g., Tolbutamide, Glibenclamide; Used in Diabetes);
• Statins (e.g., Atorvastatin, Simvastatin; Used to Lower Cholesterol Levels);
• Benzodiazepines (e.g., Midazolam, Triazolam; Used in Severe Insomnia and Stress);
• Omeprazole (Used to Treat Stomach Ulcers);
• Oral Contraceptives (If Voriconazole Fresenius Kabi Is Used with Oral Contraceptives, Side Effects Such as Nausea, Menstrual Disorders May Occur);
• 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).
• HIV Protease Inhibitors (e.g., 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), (Certain Doses of Efavirenz Should Not Be Used with Voriconazole Fresenius Kabi).
• Methadone (Used to Treat Heroin Addiction).
• Alfentanil, Fentanyl, and Other Short-Acting Opioids, Such as Sufentanil (Pain Medicines Used During Surgical Procedures).
• Oxycodone and Other Long-Acting Opioids, Such as Hydrocodone (Used for Moderate to Severe Pain).
• Non-Steroidal Anti-Inflammatory Drugs (e.g., Ibuprofen, Diclofenac; Used to Treat Pain and Inflammatory Conditions).
• Fluconazole (Used to Treat Fungal Infections).
• Everolimus (Used to Treat Advanced Kidney Cancer and in Patients After Organ Transplantation).
• Letermovir (Used to Prevent Cytomegalovirus (CMV) Disease After Bone Marrow Transplantation).
• Ivacaftor (Used to Treat Cystic Fibrosis).
• Corticosteroids, Such as Prednisolone (Used to Treat Various Diseases Involving Inflammation of the Body), Inhaled Corticosteroids, Such as Budesonide (Used to Reduce and Prevent Inflammation and Swelling of the Lungs), and Nasal Corticosteroids (Used to Treat Allergies, Congestion, and Rhinitis).

Pregnancy and Breastfeeding

Do Not Use Voriconazole Fresenius Kabi During Pregnancy, Unless Your Doctor Decides Otherwise.

During Use of Voriconazole Fresenius Kabi in Women of Childbearing Age, Effective Contraception Is Necessary. If You Become Pregnant While Taking Voriconazole Fresenius Kabi, You Should Contact Your Doctor Immediately.

If You Are Pregnant or Breastfeeding, Think You May Be Pregnant, or Plan to Have a Child, Ask Your Doctor or Pharmacist for Advice Before Taking This Medicine.

Driving and Using Machines

Voriconazole Can Cause Vision Disturbances and Discomforting Photosensitivity. If These Disturbances Occur, You Should Avoid Driving and Operating Machines. Tell Your Doctor About Their Occurrence.

Voriconazole Fresenius Kabi Contains Sodium

This Medicine Contains Up to 69 Mg of Sodium (the Main Component of Common Salt) per Vial. This Is Equivalent to 3.45% of the Maximum Recommended Daily Intake of Sodium in the Diet for Adults.

Voriconazole Fresenius Kabi Contains Cyclodextrin

This Medicine Contains 2660 Mg of Cyclodextrin per Vial.

If You Have Kidney Disease, You Should Contact Your Doctor Before Using This Medicine.

3. How to Use Voriconazole Fresenius Kabi

This Medicine Should Always Be Used Exactly as Prescribed by Your Doctor. If You Are Not Sure, Ask Your Doctor.

Your Doctor Will Choose the Dose of Voriconazole Fresenius Kabi Based on Your Body Weight and the Type of Infection.

Your Doctor May Change the Dose Depending on Your Health Condition.

The Recommended Dosage for Adult Patients (Including Elderly Patients) Is Presented in the Following Table.

Depending on the Patient's Response to Treatment, Your Doctor May Reduce the Dose to 3 Mg/Kg Body Weight Twice a Day.

If the Patient Has Mild to Moderate Liver Cirrhosis, Your Doctor May Decide to Reduce the Dose of Voriconazole Fresenius Kabi.

Use in Children and Adolescents

The Recommended Dosage for Children and Adolescents Is Presented in the Following Table.

Depending on the Patient's Response to Treatment, Your Doctor May Increase or Decrease the Daily Dose.

Voriconazole Fresenius Kabi, in the Form of Powder for Solution for Infusion, Will Be Dissolved by Hospital Staff Before Administration, and the Resulting Solution Will Be Diluted to the Appropriate Concentration (See the End of This Leaflet).

The Medicine Is Administered by Intravenous Infusion (Into a Vein) at a Maximum Rate of 3 Mg/Kg Body Weight per Hour for 1 to 3 Hours.

If You Are Using Voriconazole Fresenius Kabi to Prevent Fungal Infections, Your Treating Doctor May Stop the Administration of This Medicine If Side Effects Related to Treatment Occur.

Missing a Dose of Voriconazole Fresenius Kabi

Since This Medicine Is Administered Under the Close Supervision of Medical Staff, Missing a Dose Is Unlikely. However, If a Dose Is Missed, You Should Always Inform Your Doctor, Pharmacist, or Nurse.

Stopping Use of Voriconazole Fresenius Kabi

The Decision on How Long to Administer Voriconazole Fresenius Kabi Is Made by Your Doctor; However, Treatment with Voriconazole Fresenius Kabi Should Not Last Longer Than 6 Months.

In Patients with Impaired Immunity or Severe Infections, Long-Term Treatment May Be Necessary to Prevent Relapse of the Disease.

If There Is an Improvement in the Patient's Condition, the Route of Administration of Voriconazole Fresenius Kabi May Be Changed from Intravenous to Oral.

If Your Doctor Decides to Stop the Use of Voriconazole Fresenius Kabi, You Should Not Be Concerned About the Consequences of Stopping.

If You Have Any Further Questions About the Use of This Medicine, Ask Your Doctor, Pharmacist, or Nurse.

4. Possible Side Effects

Like All Medicines, This Medicine Can Cause Side Effects, Although Not Everybody Gets Them.

If Side Effects Occur, They Are Usually Mild and Temporary. However, Some of Them Can Be Severe and May Require Medical Attention.

Severe Side Effects – Stop Using Voriconazole Fresenius Kabi and Contact Your Doctor Immediately:

• Rash;
• Jaundice, Changes in Liver Blood Test Results;
• Pancreatitis (Which May Be Characterized by Abdominal Pain, Nausea, Vomiting).

Other Side Effects

Very Common: May Affect More Than 1 in 10 People:

• Visual Disturbances (Changes in Vision, Including Blurred Vision, Color Vision Disturbances, Photophobia, Loss of Color Vision, Eye Disorders, Glowing Vision, Night Blindness, Feeling of Shimmering, Seeing Sparks, Visual Aura, Decreased Visual Acuity, Bright Vision);
• Fever;
• Rash;
• Nausea, Vomiting, Diarrhea;
• Headache;
• Swelling of the Extremities;
• Abdominal Pain;
• Breathing Difficulties;
• Increased Liver Enzyme Activity.

Common: May Affect Up to 1 in 10 People:

• Sinusitis, Gingivitis, Chills, Weakness;
• Low Number of Certain Types of Red Blood Cells (Sometimes Associated with Immunity, May Lead to Serious Consequences) and/or White Blood Cells (Sometimes Accompanied by Fever), Low Number of Platelets, Which Help Blood to Clot;
• Low Blood Sugar, Low Potassium, Low Sodium;
• Anxiety, Depression, Confusion, Agitation, Insomnia, Hallucinations;
• Seizures, Tremors or Uncontrolled Muscle Movements, Tingling or Abnormal Sensations of the Skin, Increased Muscle Tone, Drowsiness, Dizziness;
• Bleeding in the Eye;
• Heart Rhythm Disorders, Including Very Fast or Very Slow Heartbeat, Fainting;
• Low Blood Pressure, Inflammation of the Veins (Which May Be Associated with the Formation of Blood Clots);
• Acute Breathing Difficulties, Chest Pain, Swelling of the Face (Oral Cavity, Lips, and Eyes), Fluid Retention in the Lungs;
• Constipation, Indigestion, Inflammation of the Lips;
• Jaundice, Liver Inflammation, and Liver Damage;
• Skin Rashes That Can Lead to Severe Blistering and Peeling of the Skin, Characterized by a Flat, Red Area of the Skin Covered with Small, Merging Bumps, Reddening of the Skin;
• Itching;
• Hair Loss;
• Back Pain;
• Kidney Failure, Blood in Urine, Changes in Kidney Function Tests.

Uncommon: May Affect Up to 1 in 100 People:

• Flu-Like Symptoms, Irritation and Inflammation of the Gastrointestinal Tract, Antibiotic-Associated Diarrhea, Inflammation of the Lymphatic Vessels;
• Inflammation of the Peritoneum (a Thin Tissue Lining the Inner Wall of the Abdomen and Covering the Abdominal Organs);
• Enlarged Lymph Nodes (Sometimes Painful), Bone Marrow Failure, Increased Number of Eosinophils;
• Adrenal Insufficiency, Hypothyroidism;
• Brain Disorders, Parkinson's Disease-Like Symptoms, Nerve Damage Causing Numbness, Pain, Tingling, or Burning Sensations in the Hands or Feet;
• Balance or Coordination Disorders;
• Brain Swelling;
• Double Vision, Severe Eye Diseases, Including: Eye and Eyelid Pain and Inflammation, Abnormal Eye Movements, Damage to the Optic Nerve Leading to Vision Disturbances, Swelling of the Optic Disc;
• Decreased Sensitivity to Touch;
• Taste Disorders;
• Hearing Impairment, Ringing in the Ears, Dizziness of Inner Ear Origin;
• Inflammation of Certain Internal Organs - Pancreas and Duodenum, Swelling and Inflammation of the Tongue;
• Enlargement of the Liver, Liver Failure, Gallbladder Diseases, Gallstones;
• Arthritis, Inflammation of the Veins Under the Skin (Which May Be Associated with the Formation of Blood Clots);
• Kidney Inflammation, Protein in Urine, Kidney Damage;
• Very Fast or Skipping Heartbeats, Sometimes with Irregular Electrical Impulses;
• Abnormal Electrocardiogram (ECG) Readings;
• Increased Cholesterol, Increased Urea in the Blood;
• Skin Allergic Reactions (Sometimes Severe), Including a Life-Threatening Skin Disease Characterized by Painful Blistering and Peeling of the Skin, Skin Inflammation, Hives, Sunburn or Severe Skin Reaction to Sunlight, Reddening and Irritation of the Skin, Purple or Red Skin Discoloration, Which May Be Due to a Low Number of Platelets;
• Infusion Site Reaction;
• Allergic Reaction or Excessive Immune Response.

Rare: May Affect Up to 1 in 1,000 People:

• Hyperthyroidism;
• Worsening of Brain Function, a Severe Complication of Liver Disease;
• Loss of Most of the Nerve Fibers of the Optic Nerve, Corneal Opacity, Involuntary Eye Movement;
• Bullous Rash Due to Photosensitivity;
• Disorders in Which the Immune System Attacks Part of the Peripheral Nervous System;
• Heart Rhythm Disorders or Conduction Disorders (Sometimes Life-Threatening);
• Life-Threatening Allergic Reaction;
• Blood Coagulation Disorders;
• Skin Allergic Reactions (Sometimes Severe), Including a Life-Threatening Skin Disease Characterized by Peeling of Large Areas of the Skin, Severe Skin Disease Characterized by Detachment of the Top Layer of the Skin from the Underlying Layers;
• Small, Dry, Flaking Skin Spots, Sometimes Thickened with Sharp Protrusions or "Horns".

Frequency Not Known: Cannot Be Estimated from the Available Data:

• Pigmentation and Skin Spots.

Other Important Side Effects, the Frequency of Which Is Not Known, But Which Should Be Reported to Your Doctor Immediately:

• Skin Cancer;
• Inflammation of the Tissue Surrounding the Bone;
• Red, Flaking, or Ring-Shaped Skin Changes, Which May Be a Sign of an Autoimmune Disease Called Cutaneous Lupus Erythematosus.

If You Experience Any Side Effects, Talk to Your Doctor, Pharmacist, or Nurse. Side Effects Can Also Be Reported to the Department of Drug Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products.

5. How to Store Voriconazole Fresenius Kabi

Keep This Medicine Out of the Sight and Reach of Children.

Do Not Use This Medicine After the Expiration Date Stated on the Label. The Expiration Date Refers to the Last Day of the Month.

Unopened Vial

No Special Storage Precautions Are Required.

The Solution Obtained After Dissolving Voriconazole Fresenius Kabi Should Be Used Immediately, but If Necessary, It Can Be Stored for No Longer Than 24 Hours at a Temperature of 2°C-8°C (in a Refrigerator). The Prepared Concentrate Should Be Diluted with a Compatible Infusion Solution Before Administration (See the End of This Leaflet).

Medicines Should Not Be Disposed of via Wastewater or Household Waste. Ask Your Pharmacist How to Dispose of Medicines No Longer Required. This Will Help Protect the Environment.

6. Contents of the Pack and Other Information

What Voriconazole Fresenius Kabi Contains

• The Active Substance Is Voriconazole.
• The Other Ingredients Are: Hydroxypropylbetadex (Substitution Degree: 0.58-0.68), L-Arginine, Hydrochloric Acid 6 N (to Adjust pH), Sodium Hydroxide 1 N (to Adjust pH).

Each Vial Contains 200 Mg of Voriconazole. After Dissolution According to the Recommendations by a Hospital Pharmacist or Nurse, the Concentration of Voriconazole Is 10 Mg/Ml (See the End of This Leaflet).

What Voriconazole Fresenius Kabi Looks Like and Contents of the Pack

Voriconazole Fresenius Kabi Is Available in 25 Ml Glass Vials for Single Use, in the Form of a White or Almost White, Freeze-Dried Powder for Solution for Infusion.

Package Sizes: 1 Vial or 20 Vials in a Carton.

Not All Package Sizes May Be Marketed.

Marketing Authorization Holder

Fresenius Kabi Polska Sp. z o.o.

Manufacturer

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany