Mycamine 50 mg powder for solution for infusion

Mycamine is called an antifungal medicine because it is used to treat infections caused by fungal cells. Mycamine is used to treat fungal infections caused by fungal or yeast cells called Candida . Mycamine is effective in treating systemic infections (those that have penetrated within the body). It interferes with the production of a part of the fungal cell wall. An intact cell wall is necessary for the fungus to continue living and growing. Mycamine causes defects in the fungal cell wall, making the fungus unable to live and grow.

Your doctor has prescribed Mycamine for you in the following circumstances when there are no other suitable antifungal treatments available (see section 2):

• To treat adults, adolescents and children who have a serious fungal infection called invasive candidiasis (infection that has penetrated the body).
• To treat adults and adolescents ? 16 years of age who have a fungal infection in the gullet (oesophagus) where treatment into a vein (intravenous) is appropriate.
• To treat adults, adolescents and children who are at risk of developing a Candidafungal infection that may penetrate the body.

Do not use Mycamine

• if you are allergic (hypersensitive) to micafungin or any of the other ingredients of Mycamine.

Take special care with Mycamine

In rats, long-term treatment with micafungin led to liver damage and subsequent liver tumours. The potential risk of developing liver tumours in humans is not known, and your doctor will assess the benefits and risks of Mycamine treatment before starting your medicine. Please tell your doctor if you have severe liver problems (e.g. liver failure or hepatitis) or have had abnormal liver function tests. During treatment your liver functions will be monitored more closely.

• if you have haemolytic anaemia (anaemia due to breakdown of red blood cells) or haemolysis (breakdown of red blood cells).
• if you have kidney problems (e.g. kidney failure and abnormal kidney function test). If this happens, your doctor may decide to monitor your kidney function more closely.

Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

It is especially important to inform your doctor if you are using amphotericin B desoxycholate or itraconazole (antifungal antibiotics), sirolimus (an immunosuppressant) or nifedipine (a calcium antagonist). Your doctor may decide to adjust the dose of these medicines.

Using Mycamine with food and drink
As Mycamine is given intravenously (into a vein), no restrictions on food or drink are required.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.Mycamine should not be used during pregnancy unless clearly necessary. If you use Mycamine you should not breast-feed.

Driving and using machines
There is no information on the effect of Mycamine on the ability to drive or use machines. Please inform your doctor if you experience any effects that may cause you to have problems with driving or using other machinery.

Important information about some of the ingredients of Mycamine
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Mycamine must be prepared and given to you by a doctor or another health care professional. Mycamine should be administered once daily by slow intravenous (into a vein) infusion. Your doctor will determine how much Mycamine you will receive each day.

Use in adults, adolescents ? 16 years of age and elderly

• The usual dose to treat an invasive Candida infection is 100 mg per day for patients weighing 40 kg or more and 2 mg/kg per day for patients weighing 40 kg or less.
• The dose to treat a Candida infection of the oesophagus is 150 mg for patients weighing more than 40 kg and 3 mg/kg per day for patients weighing 40 kg or less.
• The usual dose to prevent invasive Candida infections is 50 mg per day for patients weighing more than 40 kg and 1 mg/kg per day for patients weighing 40 kg or less.

Use in children (including newborns) and adolescents < 16 years of age

• The usual dose to treat an invasive Candida infection is 100 mg per day for patients weighing 40 kg or more and 2 mg/kg per day for patients weighing 40 kg or less.
• The usual dose to prevent invasive Candida infections is 50 mg per day for patients weighing more than 40 kg and 1 mg/kg per day for patients weighing 40 kg or less.

If you receive more Mycamine than you should

Your doctor monitors your response and condition to determine what dose of Mycamine is needed. However, if you are concerned that you may have been given too much Mycamine, speak to your doctor or another health care professional immediately.

If you miss a dose of Mycamine

Your doctor monitors your response and condition to determine what Mycamine treatment is needed. However, if you are concerned that you may have missed a dose, speak to your doctor or another health care professional immediately.

Effects when treatment with Mycamine is stopped

There are no known withdrawal symptoms.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, Mycamine can cause side effects, although not everybody gets them.

The safety of Mycamine has been assessed in clinical trials. Patients in these trials were critically ill, had a wide variety of other medical conditions, and required many other medicines.

Mycamine may cause the following side effects:

Common (affects 1 to 10 users in 100)

• abnormal blood tests (decreased white blood cells [leucopenia; neutropenia]); decreased red blood cells (anaemia)
• decreased potassium in the blood (hypokalaemia); decreased magnesium in the blood (hypomagnesaemia); decreased calcium in the blood (hypocalcaemia)
• headache
• inflammation of the vein wall (at injection-site)
• nausea (feeling sick); vomiting (being sick); diarrhoea; abdominal pain
• abnormal liver function tests (increased alkaline phosphatase; increased aspartate aminotransferase, increased alanine aminotransferase)
• increased bile pigment in the blood (hyperbilirubinaemia)
• rash
• fever
• rigors (shivering)

Uncommon (affects 1 to 10 users in 1,000)

• abnormal blood tests (decreased blood cells [pancytopenia]); decreased blood platelets (thrombocytopenia); increases in a certain type of white blood cells called eosinophils; decreased albumin in the blood (hypoalbuminaemia)
• allergic attack (anaphylactic reaction / anaphylactoid shock); hypersensitivity
• increased sweating
• decreased sodium in the blood (hyponatraemia); increased potassium in the blood (hyperkalaemia); decreased phosphates in the blood (hypophosphataemia); anorexia (eating disorder)
• insomnia (difficulty in sleeping); anxiety; confusion
• feeling lethargic (somnolence); trembling; dizziness; disturbed taste
• increased heart rate; stronger heartbeat; irregular heartbeat
• high or low blood pressure; skin flushing
• shortness of breath
• indigestion; constipation
• liver failure; increased liver enzymes (gamma-glutamyltransferase); jaundice (yellowing of the skin or whites of the eyes caused by liver or blood problems); reduced bile reaching the intestine (cholestasis); enlarged liver; liver inflammation
• itchy rash (urticaria); itching; skin flushing (erythema)
• abnormal kidney function tests (increased blood creatinine; increased urea in the blood); aggravated kidney failure
• increase in an enzyme called lactate dehydrogenase
• clotting in vein at injection-site; inflammation at injection-site; pain at injection-site; collection of fluid in your body

Rare (affects 1 to 10 users in 10,000)

• anaemia due to breakdown of red blood cells (haemolytic anaemia), breakdown of red blood cells (haemolysis)

Not known (frequency cannot be estimated from the available data)

• shock
• damage to liver cells including death
• severe skin reaction
• kidney problems; acute kidney failure

The following reactions have been reported more often in paediatric patients than in adult patients: Common (affects 1 to 10 users in 100)

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

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Mycamine after the expiry date which is stated on the vial and on the carton. The expiry date refers to the last day of that month.

The unopened vial does not require any special storage conditions.
The reconstituted concentrate and the diluted infusion solution should be used immediately.

Do not use the diluted infusion solution if it is cloudy or precipitated.

In order to protect the infusion bottle / bag containing the diluted infusion solution from light it should be inserted into a closable opaque bag.

The vial is for single use only. Therefore, please discard unused reconstituted concentrate immediately.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Reconstituted Mycamine should be used immediately because it does not contain any preservatives to prevent bacterial contamination. Only a trained health care professional who has read the complete directions properly can prepare this medicine for use.

What Mycamine contains

• The active substance is micafungin sodium. 1 vial contains 50 mg or 100 mg micafungin (as sodium).
• The other ingredients are lactose monohydrate, citric acid anhydrous and sodium hydroxide.

What Mycamine looks like and contents of the pack

Mycamine 50 mg or 100 mg powder for solution for infusion is a white compact freeze-dried powder. Mycamine is supplied in a box containing 1 vial.

Marketing Authorisation Holder

Astellas Pharma Europe B.V.
Elisabethhof 19
2353 EW Leiderdorp
Netherlands

Manufacturer

Astellas Ireland Co., Ltd.
Killorglin, County Kerry
Ireland

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Astellas Pharma B.V. Branch Erasmus ParkParc Erasme Square Marie Curie 50 B-1070 BrüsselBruxelles TélTel 32 02 5580710 . 6 1407 Te. 359 2 862 53 72 LuxembourgLuxemburg Astellas Pharma B.V. Branch Erasmus ParkParc Erasme Square Marie Curie 50 B-1070 BrüsselBruxelles BelgiqueBelgien TélTel 32 02 5580710 Magyarország Astellas Pharma Kft. Kelenhegyi út 43 H-1118 BudapestB.III Tel. 36 061 3614673

eská republika Astellas Pharma s.r.o. Sokolovskà 10094 CZ-18600 Praha 8 Tel 420 236 080300 Malta E.J. Busuttil Ltd. Niche Triq ix-Xorrox MT-Bkara BKP 12 Tel 356 21 447184

Danmark Astellas Pharma as Naverland 4 DK-2600 Glostrup Tlf 45 43430355 Nederland Astellas Pharma B.V. Elisabethhof 19 NL-2353 EW Leiderdorp Tel 31 071 5455745

Deutschland Astellas Pharma GmbH Georg-Brauchle-Ring 64 66 D-80992 München Tel 49 089 454401 Norge Astellas Pharma Solbråveien 47 N-1383 Asker Tlf 47 6676 4600

Eesti Astellas Pharma Europe B.V. Elisabethhof 19 NL-2353 EW Leiderdorp Österreich Astellas Pharma Ges.m.b.H. Linzer Straße 221E02 A-1140 Wien

Tel 43 01 8772668 Holland Tel 31 071 5455745 Astellas Pharmaceuticals AEBE 1 GR-14565, T 30 210 8189900 Polska Astellas Pharma Sp.z o.o. ul. Poleczki 21 PL-02-822 Warszawa Tel. 48 0 225451 111

España Astellas Pharma S.A. Paseo del Club Deportivo n 1 Bloque 14-2a Planta E-28223 Pozuelo de Alarcón, Madrid Tel 34 91 4952700 Portugal Astellas Farma, Lda. Edifício Cinema Rua José Fontana, n.1, 1Andar P-2770-101 Paço de Arcos Tel 351 21 4401320

France Astellas Pharma S.A.S. 114 rue Victor Hugo F-92300 Levallois Perret Tél 33 01 55917500 România S.C.Astellas Pharma SRL Detalii de contact pentru România oseaua Bucureti-Ploieti 42-44 Cldire 1, Parter 013696-Bucureti - RO Tel 40 021 361 04 95

Slovenija Astellas Pharma Europe B.V. Elisabethhof 19 NL-2353 EW Leiderdorp Nizozemska Tel 31 071 5455745 Ireland Astellas Pharma Co. Ltd. 25, The Courtyard Kilcarbery Business Park Nangor Road Clondalkin IRL-Dublin 22 Tel 353 01 4671555

Ísland Vistor hf. Hörgatúni 2 IS-210 Garðabær Tel 354 535 7000 Slovenská republika Astellas Pharma s.r.o., organizaná zloka Galvániho 15C SK-821 04 Bratislava Tel 421 2 4444 2157

Italia Astellas Pharma S.p.A. Via delle Industrie 1 I-20061 Carugate Milano Tel 39 02 921381 SuomiFinland Algol Pharma Oy PL 13 FIN-02611 EspooEsbo PuhTel 358 9 50991

Sverige Astellas Pharma AB Per Albin Hanssons väg 41 S-205 12 Malmö Tel 46 040-650 15 00 Astellas Pharmaceuticals AEBE 1 GR-14565, T 30 210 8189900

Latvija Astellas Pharma Europe B.V. Elisabethhof 19 NL-2353 EW Leiderdorp Nderlande Tel 31 071 5455745 United Kingdom Astellas Pharma Ltd. Lovett House Lovett Road, Staines Middlesex, TW18 3AZ Tel 44 0 1784 419615

Lietuva
Astellas Pharma Europe B.V.
Elisabethhof 19
NL-2353 EW Leiderdorp
Nyderlandai
Tel: +31 (0)71 5455745

This leaflet was last approved in {MM/YYYY}.

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The following information is intended for medical or healthcare professionals only:

Mycamine must not be mixed or co-infused with other medicinal products except those mentioned below. Using aseptic techniques at room temperature, Mycamine is reconstituted and diluted as follows:

1. The plastic cap must be removed from the vial and the stopper disinfected with alcohol.

2. Five ml of sodium chloride 9 mg/ml (0.9%) solution for infusion or glucose 50 mg/ml (5%) solution for infusion (taken from a 100 ml bottle/bag) should be aseptically and slowly injected into each vial along the side of the inner wall. Although the concentrate will foam, every effort should be made to minimise the amount of foam generated. A sufficient number of vials of Mycamine must be reconstituted to obtain the required dose in mg (see table below).

3. The vial should be rotated gently. DO NOT SHAKE. The powder will dissolve completely. The concentrate should be used immediately. The vial is for single use only. Therefore, please discard unused reconstituted concentrate immediately.

4. All of the reconstituted concentrate should be withdrawn from each vial and returned into the infusion bottle/bag from which it was originally taken. The diluted infusion solution should be used immediately. Chemical and physical in-use stability have been demonstrated for 96 hours at 25°C when protected from light and diluted as described above.

5. The infusion bottle/bag should be gently inverted to disperse the diluted solution but NOT agitated in order to avoid foaming. Do not use if the solution is cloudy or has precipitated.

6. The infusion bottle/bag containing the diluted infusion solution should be inserted into a closable opaque bag for protection from light.

Preparation of the solution for infusion

Dose mg Mycamine vial to be used mgvial Volume of sodium chloride 0.9 or glucose 5 to be added per vial Volume concentration of reconstituted powder Standard infusion added up to 100 ml Final concentration 50 1 x 50 5 ml 0.5 mgml approx. 5 ml 10 mgml 100 1 x 100 5 ml 1.0 mgml approx. 5 ml 20 mgml 150 5 ml approx. 10 ml 1.5 mgml 1 x 100 1 x 50 200 2 x 100 5 ml approx. 10 ml 2.0 mgml

ANNEX IV

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT TO BE IMPLEMENTED BY THE MEMBER STATES

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF MEDICINAL PRODUCT TO BE IMPLEMENTED BY THE MEMBER STATES

The Member States should ensure that all conditions or restrictions with regard to the safe and effective use of the medicinal product described below i.e. the details of a prescription checklist are implemented:

• Mycamine is contra-indicated if the patient has a history of hypersensitivity to micafungin or excipients.
• Mycamine should not be used during pregnancy unless clearly necessary.
• Caution must be demonstrated if the patient:
• has severe liver function impairment
• has chronic liver diseases known to represent preneoplastic conditions (e.g. advanced liver fibrosis, cirrhosis, viral hepatitis, neonatal liver disease or congenital enzyme defects)
• is receiving a concomitant therapy including hepatotoxic and/or genotoxic properties
• has history of haemolysis, haemolytic anaemia or renal impairment.
• Patients receiving sirolimus, nifedipine or itraconazole in combination with Mycamine should be monitored for sirolimus, nifedipine or itraconazole toxicity and the sirolimus, nifedipine or itraconazole dosage should be reduced if necessary.
• Patients should be carefully monitored for liver damage and for worsening of renal function.
• To minimise the risk of adaptive regeneration and potentially subsequent liver tumour formation, early discontinuation in the presence of significant and persistent elevation of ALT/AST is recommended.