Fungizone

Package Leaflet: Information for the Patient

Fungizone, 50 mg, Powder for Solution for Infusion

Amphotericin B

Read the Package Leaflet Carefully Before Using the Medication, as it Contains Important Information for the Patient.

• Keep this Package Leaflet, as You May Need to Read it Again.
• In Case of Any Doubts, Consult a Doctor, Pharmacist, or Nurse.
• This Medication has been Prescribed to a Specific Person. Do Not Pass it on to Others. The Medication may Harm Another Person, even if their Symptoms are the Same.
• If the Patient Experiences any Undesirable Effects, Including any Undesirable Effects not Listed in this Package Leaflet, Inform a Doctor, Pharmacist, or Nurse. See Section 4.

Package Leaflet Contents

• 1. What is Fungizone and What is it Used for
• 2. Important Information Before Using Fungizone
• 3. How to Use Fungizone
• 4. Possible Undesirable Effects
• 5. How to Store Fungizone
• 6. Package Contents and Other Information

1. What is Fungizone and What is it Used for

Fungizone is a Powder for Solution for Infusion. The Active Substance is Amphotericin B, an Antifungal Antibiotic Used to Treat Fungal Infections. Fungizone is Used to Treat Patients with Severe, Life-Threatening Fungal Infections.

2. Important Information Before Using Fungizone

When Not to Use Fungizone:

• If the Patient is Allergic to Amphotericin B or any of the Other Ingredients of this Medication (Listed in Section 6), Except in Cases where the Doctor has Determined that the Patient's Life is at Risk and Amphotericin B is the Only Possible Treatment.

Warnings and Precautions

In Life-Threatening Fungal Infections, the Only Effective Treatment may be the Administration of Amphotericin B. The Doctor must Weigh the Benefits of Saving a Life Against the Risks of Unexpected and Dangerous Undesirable Effects. Amphotericin B should be Administered by Trained Medical Personnel, Only Intravenously, and Only to Patients Under Close Clinical Supervision. During Intravenous Administration of Amphotericin B, Acute Reactions such as Chills, Fever, Loss of Appetite, Nausea, Vomiting, Headache, Muscle Pain, Joint Pain, and Low Blood Pressure Often Occur. Rapid Intravenous Infusion, Administered in Less than 1 Hour, should be Avoided, as it may Cause High Potassium Levels in the Blood and Cardiac Arrhythmias, Especially in Patients with Renal Failure. After Treatment with Amphotericin B, Damage to the White Matter of the Brain (Leukoencephalopathy) has been Observed in Patients Undergoing Whole-Body Irradiation. During Treatment, the Doctor may Order Laboratory Tests and Modify the Treatment Based on the Results. Cases of Neurological Symptoms (Meningitis, Spinal Cord Damage, Paresis, Paralysis) have been Reported After Administration of the Medication into the Space Surrounding the Spinal Cord (Intrathecally).

Fungizone and Other Medications

Inform the Doctor or Nurse About all Medications the Patient is Currently Taking or has Recently Taken, as well as any Medications the Patient Plans to Take. Some Medications Used in Combination with Fungizone may Affect its Action. This is Especially Important if the Patient is Taking:

• Medications that can Damage the Kidneys:
• Cisplatin (Anticancer Medications),
• Cyclosporin (Medication Used After Organ Transplantation and in the Treatment of Autoimmune Diseases),
• Aminoglycoside Antibiotics (e.g., Gentamicin, Vancomycin),
• Pentamidine (Antiprotozoal Medication);
• Muscle Relaxants (e.g., Baclofen, Diazepam);
• Corticosteroids (e.g., Hydrocortisone) and Corticotropin (ACTH);
• Cardiac Glycosides (e.g., Digoxin);
• Medications Used to Treat Heart Rhythm Disorders (e.g., Quinidine);
• Flucytosine (Antifungal Medication);
• The Patient has Received White Blood Cell Transfusions (Leukocytes).

Pregnancy and Breastfeeding

If the Patient is Pregnant or Breastfeeding, or Thinks they may be Pregnant or Plans to Have a Child, they should Consult a Doctor Before Using this Medication. Pregnancy The Medication may be Used During Pregnancy with Special Caution, if the Doctor Decides that the Expected Benefit to the Mother Outweighs the Risk to the Fetus. Breastfeeding It is not Known if Amphotericin B Passes into Human Breast Milk. Breastfeeding Mothers are Advised to Stop Breastfeeding.

Driving and Operating Machinery

The Effect of the Medication on the Ability to Drive and Operate Machinery has not been Studied. The Doctor will Inform the Patient About the Precautions to be Taken when Performing these Activities, as Undesirable Effects may Occur that Affect Physical and Mental Performance, such as Dizziness, Vision Disturbances, Headache, or other Neurological Symptoms, Hypotension, and other Severe Undesirable Effects. If the Patient has any Further Questions About the Use of Fungizone, they should Consult a Doctor or Healthcare Professional Involved in their Care.

Sodium Content

The Medication Contains Less than 1 mmol (23 mg) of Sodium per Vial, i.e., the Medication is Considered "Sodium-Free". Natural Rubber (Latex)The Medication Packaging Contains Latex. It may Cause Severe Allergic Reactions.

3. How to Use Fungizone

Fungizone is Administered to the Patient by a Doctor or Healthcare Professional. In Case of Doubts About the Dose of the Medication, Consult the Person Administering the Infusion. The Dosage of Fungizone is Determined by the Doctor Individually, Depending on the Disease. The Daily Dose is 0.25-1.5 mg/kg Body Weight. The Patient Receives the Medication in a Slow Intravenous Infusion (Drip Infusion into a Vein Using a Cannula). This Usually Takes 2 to 6 Hours. Before Starting Treatment, the Patient may Receive a Small, Test Dose of the Medication. Treatment Usually Lasts Several Months, Until the Infection has Completely Disappeared. The Patient must not Receive a Dose Greater than 1.5 mg/kg Body Weight in 24 Hours. Overdose of Amphotericin B may Cause Cardiac Arrest, Respiratory Arrest, or Circulatory Arrest, with Possible Fatal Outcome.

Use in Children and Adolescents

The Safety and Efficacy of Amphotericin B have not been Confirmed by Adequate and Well-Controlled Studies. During Treatment of Systemic Fungal Infections in Children, no Unusual Undesirable Effects have been Observed.

Use of a Higher than Recommended Dose of Fungizone

Under no Circumstances should the Total Daily Dose of 1.5 mg/kg Body Weight be Exceeded. Use of a Higher than Recommended Dose of Fungizone may Cause Cardiac Arrest or Circulatory Arrest and Respiratory Arrest, with Possible Fatal Outcome. If a Higher than Recommended Dose of Fungizone is Used, Treatment should be Discontinued and the Patient's Clinical Condition should be Monitored.

Missing a Dose of Fungizone

A Double Dose should not be Used to Make up for a Missed Dose.

Discontinuing Fungizone

In Case of any Further Doubts About the Use of this Medication, Consult a Doctor or Pharmacist.

4. Possible Undesirable Effects

Like all Medications, Fungizone can Cause Undesirable Effects, although not Everybody gets them. The Use of Fungizone may Affect Blood Cells, Kidneys, Liver, and Heart. Therefore, the Doctor will Check their Function Before Starting Treatment, During Treatment, and After Completion of Treatment. Inform the Doctor Immediately if any of the Following Symptoms Occur:

• Swelling of the Face, Lips, or Tongue,
• Skin Symptoms, such as Severe Rash, Itching,
• Breathing Difficulties, as these Symptoms may be Signs of a Severe Allergic Reaction.

Patients have Reported Blood System Disorders, which may be Accompanied by Fever or Chills, Sore Throat, Mouth Ulcers, Fatigue, or Weakness, Unusual Bleeding or Unexplained Bruising. If the Patient Notices any such Symptoms, they must Inform the Doctor Immediately. The Use of Fungizone may Cause Kidney Damage. If the Patient Notices that they are more Thirsty than Usual, Need to Urinate more Often, or that the Amount of Urine has Increased, they should Contact the Doctor Immediately. The Following Symptoms may Occur During Treatment.

Very Common(may Affect more than 1 in 10 Patients):

• Nausea, Vomiting,
• Fever, Chills
• Potassium Level Decrease, Creatinine Level Increase in the Blood
• Kidney Function Disorders
• Shortness of Breath
• Low Blood Pressure

Common(may Affect up to 1 in 10 Patients):

• Anemia,
• Liver Function Disorders
• Magnesium Level Decrease in the Blood
• Rash

Uncommon(may Affect up to 1 in 100 Patients):

• Decrease or Increase in the Number of Certain White Blood Cells (Agranulocytosis, Eosinophilia, Leukocytosis, Leukopenia)
• Platelet Count Decrease
• Blood Coagulation Disorders
• Heat Stroke

Occurring with Unknown Frequency(Frequency that cannot be Estimated from Available Data):

• Heart Rhythm Disorders, Cardiac Arrest, Heart Failure
• Hearing Loss, Ringing in the Ears
• Dizziness
• Double or Blurred Vision
• Indigestion, Severe Abdominal Pain (Cramps), Gastrointestinal Inflammation with Bleeding
• Diarrhea
• Black Stools (Blood in Stool)
• Pain, Malaise
• Pain at the Injection Site, with or without Phlebitis or Thrombophlebitis
• Acute Liver Failure, Jaundice
• Anaphylactic Reactions and other Allergic Reactions
• Potassium Level Increase in the Blood
• Weight Loss
• Loss of Appetite
• Joint Pain, Muscle Pain
• Seizures, Headache, Brain Damage (Encephalopathy) and other Neurological Disorders, Peripheral Nerve Damage (Neuropathy)
• Kidney Function Disorders of Various Degrees, Acute Kidney Failure
• Allergic Pneumonia, Bronchospasm, Pulmonary Edema
• Severe Allergic Skin Reactions, with Blisters, Peeling, and Itching
• Blood Pressure Increase, Shock.

Reporting Undesirable Effects If any Undesirable Effects Occur, including any Undesirable Effects not Listed in this Package Leaflet, Inform a Doctor or Pharmacist. Undesirable Effects can be Reported Directly to the Department of Monitoring of Undesirable Effects of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products Al. Jerozolimskie 181C 02-222 Warsaw Tel.: +48 22 49 21 301 Fax: +48 22 49 21 309 Website: https://smz.ezdrowie.gov.pl Undesirable Effects can also be Reported to the Marketing Authorization Holder. By Reporting Undesirable Effects, more Information can be Collected on the Safety of the Medication.

5. How to Store Fungizone

Store the Medication in a Place that is Inaccessible to Children. Store in a Refrigerator at a Temperature of 2°C-8°C. Do not Use this Medication After the Expiry Date Stated on the Label and Carton after ‘Expiry Date’. The Expiry Date Refers to the Last Day of the Month. Medications should not be Disposed of via Wastewater or Household Waste. Ask a Pharmacist how to Dispose of Medications that are no Longer Needed. This will Help Protect the Environment.

6. Package Contents and Other Information

What Fungizone Contains

• The Active Substance is Amphotericin B. 1 Vial Contains 50 mg of Amphotericin B. The Other Ingredients are Sodium Dihydrogen Phosphate Dihydrate, Disodium Phosphate Dodecahydrate, Deoxycholic Acid, Sodium Hydroxide (for pH Adjustment), Phosphoric Acid (for pH Adjustment).

What Fungizone Looks Like and What the Package Contains

Lyophilized Powder of Yellow to Orange Color. Vial Made of Colorless Glass Type I with a Cork Made of Chlorobutyl Rubber and an Aluminum Cap and a Polypropylene Flip-Off Cap, in a Cardboard Box. The Package Contains 1 Vial Containing 50 mg of Amphotericin B.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

CHEPLAPHARM Arzneimittel GmbH Ziegelhof 24 17489 Greifswald Germany

Manufacturer

Delpharm Saint Remy Usine de Saint Rémy-rue de l’Isle 28380 Saint-Rémy-Sur-Avre, France For More Detailed Information on this Medication, Contact the Marketing Authorization Holder.

Date of Last Update of the Package Leaflet: -------------------------------------------------------------------------------------------------------------------------------------------

Information Intended for Healthcare Professionals Only

Preparing the Concentrate The Amphotericin B Concentrate with a Concentration of 5 mg/ml is Prepared by Quickly Injecting 10 ml of Distilled Water for Injection without a Bacteriostatic Agent into the Vial with the Lyophilizate, Using a Sterile Syringe and Needle (Minimum Diameter: 20 G). Immediately Start Shaking the Vial to Obtain a Clear Colloidal Dispersion. Preparing the Infusion Solution To Prepare the Infusion Solution, Take the Required Amount of Concentrate and Dilute it with 5% Glucose Solution so that the Final Concentration of Amphotericin B is 0.1 mg/ml. Before Using the Glucose Solution, Check its pH, which should be Above 4.2. Glucose Solutions Available on the Market Usually have a pH Above 4.2; However, if the pH is Lower than 4.2, Add 1 or 2 ml of Buffer to the Glucose Solution Before Using it to Dilute the Amphotericin B Solution. The Composition of the Recommended Buffer is as Follows: Disodium Hydrogen Phosphate (Anhydrous) 1.59 g Sodium Dihydrogen Phosphate (Anhydrous) 0.96 g Water for Injection qs ad 100 ml Before Adding the Buffer to the Glucose Solution, Sterilize it by Passing it Through a Bacteria-Retaining Porcelain, Mat, or Membrane Filter or by Autoclaving for 30 Minutes at a Pressure of 106 kPa (15 lb), (121°C). Warning. Both During the Preparation of the Buffer and During the Infusion, Strictly Follow the Rules of Asepsis!, as Neither the Antibiotic nor the Solvent Contains Preservatives or Bacteriostatic Agents. All Punctures of the Vial with the Powder or the Solvent should be Made Using a Sterile Needle. Do not Use Physiological Sodium Chloride Solution (0.9%) to Prepare the Solution. Using a Different Solvent than Recommended or the Presence of a Bacteriostatic Agent (e.g., Benzyl Alcohol) in the Solvent may Cause the Antibiotic to Precipitate. Do not Use the Concentrate or Infusion Solution if a Precipitate or Foreign Body is Found in Either of them. To Perform the Intravenous Infusion of Amphotericin B, a Linear Filter can be Used; However, the Average Pore Diameter of the Filter should not be Less than 1.0 Micron to Ensure that the Colloidal Dispersion Passes Through it.