Micafungin day zero

Patient Information Leaflet

Micafungin Day Zero, 50 mg, powder for solution for infusion
Micafungin Day Zero, 100 mg, powder for solution for infusion
Micafunginum
Please read all of this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of Contents

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

1. What Micafungin Day Zero is and what it is used for

Micafungin Day Zero contains the active substance micafungin. Micafungin Day Zero is known as an antifungal medicine because it is used to treat infections caused by fungal cells.
Micafungin Day Zero is used to treat fungal infections caused by fungi or yeast-like organisms called Candida. Micafungin Day Zero is effective in treating systemic infections (those that have spread into the body). It acts by interfering with the formation of a component of the fungal cell wall. An intact cell wall is essential for the normal development and growth of fungal cells. Micafungin Day Zero damages the fungal cell wall, thereby preventing further development and growth of fungi.
Your doctor may prescribe Micafungin Day Zero in the following situations, when no other appropriate antifungal treatment is available (see section 2):

• Treatment of adults, adolescents, and children, including newborns, with a serious fungal infection called invasive candidiasis (an infection that spreads into the body);
• Treatment of adults and adolescents aged ≥ 16 years with fungal infection of the oesophagus (oesophageal candidiasis) where intravenous treatment (administration into a vein) is appropriate;
• Prevention of Candida infections in patients undergoing allogeneic haematopoietic stem cell transplantation or in patients expected to have neutropenia (low levels of neutrophils; a type of white blood cell) lasting for 10 or more days.

2. Important information before using Micafungin Day Zero

When not to use Micafungin Day Zero

• if the patient is allergic to micafungin, other echinocandins ( Ecalta or Cancidas ), or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Long-term treatment with micafungin in rats has led to liver damage and, consequently, to liver tumours. The potential risk of developing liver tumours in humans is unknown; before starting treatment, the doctor will assess the benefits and risks of using Micafungin Day Zero. You should tell the doctor if the patient has severe liver disease (e.g. liver failure or hepatitis) or if abnormal liver function test results have been observed. Liver function will be monitored more closely during treatment.
Before starting treatment with Micafungin Day Zero, discuss this with the doctor or
pharmacist

• if the patient is allergic to any medicine;
• if the patient has haemolytic anaemia (anaemia caused by the breakdown of red blood cells) or haemolysis (breakdown of red blood cells);
• if the patient has kidney disease (e.g. kidney failure or abnormal kidney function test results). In such cases, the doctor may recommend closer monitoring of kidney function.

Micafungin may also cause severe inflammation and (or) skin and mucous membrane rashes
(Stevens-Johnson syndrome, toxic epidermal necrolysis [Lyell's syndrome]).
Micafungin Day Zero and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
It is especially important to inform the doctor about the use of amphotericin B deoxycholate or
itraconazole (antifungal antibiotics), sirolimus (an immunosuppressive medicine), or nifedipine
(calcium channel blocker used in the treatment of hypertension). The doctor may decide
to adjust the dose of these medicines.
Micafungin Day Zero with food and drink
Since Micafungin Day Zero is administered intravenously (into a vein), there are no restrictions
regarding food and drink intake.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have
a child, she should consult a doctor or pharmacist before using this medicine.
Micafungin Day Zero must not be used during pregnancy unless absolutely necessary, as determined by the doctor.
Breastfeeding must not be undertaken during treatment with Micafungin Day Zero.
Driving and operating machinery
It is unlikely that micafungin will affect the ability to drive or operate machinery. However, dizziness may occur in some patients during treatment with this medicine, and in such cases, the patient should not drive or operate machinery.
Inform the doctor if any side effects occur that may impair the ability to drive or operate machinery.
Micafungin Day Zero contains sodium
Micafungin Day Zero contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

3. How to use Micafungin Day Zero

Micafungin Day Zero must be prepared and administered by a physician or other medical personnel. Micafungin Day Zero should be given once daily as a slow intravenous infusion (into a vein). The daily dose of the medication will be determined by the treating physician.

Use in adults, adolescents aged ≥ 16 years, and elderly patients

• For the treatment of invasive Candida infection, the usual dose is 100 mg once daily in patients weighing more than 40 kg and 2 mg/kg body weight once daily in patients weighing 40 kg or less.
• For the treatment of Candida esophagitis, the daily dose is 150 mg in patients weighing more than 40 kg and 3 mg/kg body weight once daily in patients weighing 40 kg or less.
• For prophylaxis of invasive infections caused by Candida, the usual dose is 50 mg once daily in patients weighing more than 40 kg and 1 mg/kg body weight once daily in patients weighing 40 kg or less.

Use in children aged > 4 months and adolescents aged < 16 years

• For the treatment of invasive Candida infection, the usual dose is 100 mg once daily in patients weighing more than 40 kg and 2 mg/kg body weight once daily in patients weighing 40 kg or less.
• For prophylaxis of invasive infections caused by Candida, the usual dose is 50 mg once daily in patients weighing more than 40 kg and 1 mg/kg body weight once daily in patients weighing 40 kg or less.

Use in children and neonates aged < 4 months

• For the treatment of invasive Candida infection, the usual dose ranges from 4 mg/kg to 10 mg/kg body weight once daily.
• For prophylaxis of invasive infections caused by Candida, the usual dose is 2 mg/kg body weight once daily.

Use of a higher than recommended dose of Micafungin Day Zero
The physician will determine the appropriate dose of Micafungin Day Zero based on the patient's response to treatment and clinical condition. If there is any doubt whether too high a dose of Micafungin Day Zero has been administered, contact the physician or other medical personnel immediately.

Missed dose of Micafungin Day Zero
The physician will decide on the need for continued treatment with Micafungin Day Zero based on the patient's response to treatment and clinical condition. If there is any doubt whether a dose of Micafungin Day Zero has been missed, contact the physician or other medical personnel immediately.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody gets them.
If you experience an allergic reaction or a severe skin reaction (e.g. blistering or peeling of the skin), inform your doctor or nurse immediately.
Micafungin Day Zero may cause the following other adverse reactions:
Common (may occur in up to 1 in 10 patients)

• abnormal blood test results (decreased number of white blood cells [leukopenia; neutropenia]); decreased number of red blood cells (anaemia);
• low blood potassium levels (hypokalaemia); low blood magnesium levels (hypomagnesaemia); low blood calcium levels (hypocalcaemia);
• headache;
• inflammation of the vein wall (at the injection site);
• nausea (feeling sick); vomiting; diarrhoea; abdominal pain;
• abnormal liver function test results (increased alkaline phosphatase activity, increased aspartate aminotransferase activity, increased alanine aminotransferase activity);
• increased level of bile pigment in the blood (hyperbilirubinaemia);
• rash;
• fever;
• rigors (chills).

Uncommon (may occur in up to 1 in 100 patients)

• abnormal blood test results (decreased number of blood cells [pancytopenia]); decreased number of platelets (thrombocytopenia); increased number of a certain type of white blood cells called eosinophils; decreased level of albumin in the blood (hypoalbuminaemia);
• hypersensitivity;
• increased sweating;
• low blood sodium levels (hyponatraemia); high blood potassium levels (hyperkalaemia); low blood phosphate levels (hypophosphataemia); anorexia (eating disorders);
• insomnia (sleep problems); anxiety; disorientation;
• drowsiness (somnolence); tremor; dizziness; taste disturbance;
• rapid heartbeat; stronger heartbeat; irregular heartbeat;
• high or low blood pressure; skin redness;
• shortness of breath;
• indigestion; constipation;
• liver failure; increased liver enzyme activity (gamma-glutamyl transferase); jaundice (yellowing of the skin or whites of the eyes due to liver or blood disorders); reduced bile excretion into the intestine (cholestasis); enlarged liver; hepatitis;
• itchy rash (urticaria); itching; skin redness (erythema);
• abnormal kidney function test results (increased blood creatinine levels; increased blood urea levels); worsening of kidney failure;
• increased activity of an enzyme called lactate dehydrogenase;
• thrombosis of the vein at the injection site; inflammation at the injection site; pain at the injection site; fluid retention in the body.

Rare (may occur in up to 1 in 1,000 patients)

• anaemia caused by breakdown of red blood cells (haemolytic anaemia), breakdown of red blood cells (haemolysis).

Unknown (frequency cannot be estimated from the available data)

• blood coagulation disorder;
• shock (allergic);
• liver cell damage, which may also lead to death;
• kidney problems; acute kidney failure.

Additional adverse reactions observed in children and adolescents
The following reactions have been observed more frequently in children and adolescents than in adult patients:
Common (may occur in up to 1 in 10 patients)

• decreased number of platelets (thrombocytopenia);
• increased heart rate (tachycardia);
• high or low blood pressure;
• increased bile pigment in the blood (hyperbilirubinaemia); enlarged liver;
• acute kidney failure; increased blood urea levels.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions to 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Micafungin Day Zero

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of the specified month.
Unopened vials do not require storage under special conditions.

Concentrate prepared in a vial:
The prepared concentrate maintains its chemical and physical stability for 48 hours at 25°C when prepared using sodium chloride solution 9 mg/ml (0.9%) for infusion or glucose solution 50 mg/ml (5%) for infusion.

Diluted infusion solution:
The prepared diluted solution maintains its chemical and physical stability for 96 hours at 25°C provided it is protected from light and diluted with sodium chloride solution 9 mg/ml (0.9%) for infusion or glucose solution 50 mg/ml (5%) for infusion.

From a microbiological standpoint, the reconstituted and diluted solutions should be used immediately after preparation. If not administered immediately, responsibility for storage conditions and duration lies with the person administering the medicine. The storage time should not exceed 24 hours at a temperature of 2 to 8°C, unless reconstitution and dilution were carried out under controlled and validated aseptic conditions.

This medicine must be prepared for use only by trained healthcare personnel after carefully reading the entire instruction leaflet.

Do not use the diluted solution if it becomes cloudy or contains particulate matter.

To protect from light, the bottle (or bag) containing the diluted solution should be placed in a closed, opaque cover.

The vial is intended for single use only. Any unused, prepared concentrate must be discarded immediately.

Medicines must 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 package and other information

What Micafungin Day Zero contains

• The active substance is micafungin (as the sodium salt). One vial contains sodium salt of micafungin equivalent to 50 mg or 100 mg of micafungin.
• The other components are: sucrose, citric acid, and sodium hydroxide.

What Micafungin Day Zero looks like and contents of the pack
Micafungin Day Zero 50 mg or 100 mg is a white or almost white powder for solution for infusion.
Micafungin Day Zero is supplied in packs containing 1 vial.

Marketing Authorisation Holder
Day Zero ehf,
Reykjavíkurvegi 62
220 Hafnarfjordur
Iceland

Manufacturer
Actavis Italy S.p.A - Nerviano Plant
Via Pasteur 10
20014 Nerviano (Milan),
Italy
S.C. Sindan-Pharma S.R.L.
11 Ion Mihalache Ave.,
1st district Bucharest 011171,
Romania

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria Micafungin Day Zero 50 mg Powder for solution for infusion
Micafungin Day Zero 100 mg Powder for solution for infusion
Poland Micafungin Day Zero

Information intended exclusively for medical professionals:

Micafungin Day Zero must not be mixed or administered simultaneously in the same infusion with other medicinal products, except those listed below. Under aseptic conditions and at room temperature, Micafungin Day Zero should be prepared as follows:

1. Remove the plastic cap from the vial and disinfect the rubber stopper with alcohol.
2. Under aseptic conditions, slowly inject 5 ml of sodium chloride 9 mg/ml (0.9%) for infusion or glucose 50 mg/ml (5%) for infusion (drawn from a 100 ml bottle/bag) down the inner wall of each vial. Although foaming may occur, every effort should be made to minimize foam formation. To obtain the correct dose of Micafungin Day Zero in mg, prepare the concentrate using the appropriate number of vials (see table below).
3. Gently rotate the vial along its long axis. DO NOT SHAKE! The powder will dissolve completely. The prepared concentrate should be used immediately. The vial is for single use only. Any prepared but unused concentrate must be discarded immediately.
4. Transfer the entire volume of the prepared concentrate from the vials into the bottle (bag) containing the infusion solution from which the solution was originally withdrawn. The diluted infusion solution should be administered immediately. The prepared solution remains chemically and physically stable for 96 hours at 25°C, provided it is protected from light and diluted according to the instructions above.
5. Gently invert the bottle (bag) to ensure thorough mixing of the diluted solution and DO NOT SHAKE to avoid foaming. After dilution, the solution should be clear, colorless, and free from visible particles. Only use solutions that are clear, colorless, and free from visible particles. Do not administer the solution if it is cloudy or contains a precipitate.
6. Place the bag (bottle) containing the diluted solution in a closed, opaque bag to protect it from light.

Preparation of the infusion solution

After reconstitution and dilution, the solution should be administered by slow intravenous infusion lasting approximately 1 hour.