AMBISOME 50 mg Порошок Для Раствора Для Внутривенного Введения

Содержание инструкции

1. AmBisome liposomal 50 mg powder for dispersion for infusion
   1. What is AmBisome and what is it used for
   2. What you need to know before using AmBisome
   3. How to use AmBisome
   4. Possible side effects
   5. How to store AmBisome
   6. Contents of the pack and other information

AmBisome liposomal 50 mg powder for dispersion for infusion

Read this leaflet carefully before you use 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, pharmacist or nurse.
• This medicine has been prescribed only for you. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is AmBisome and what is it used for

AmBisome contains the active substance Amphotericin B which is administered by infusion for the
treatment of:

• suspected fungal infections in patients with febrile neutropenia (a condition of low levels of neutrophils, a type of white blood cells, combined with fever)
• severe systemic and/or deep mycoses (fungal infections) such as: candidiasis, aspergillosis, mucormycosis, chronic mycetoma and cryptococcal meningitis associated with HIV.

AmBisome may also be effective in the following fungal infections:

• North American blastomycosis
• coccidioidomycosis
• histoplasmosis, mucormycosis caused by species of the genera Mucor, Rhizopus, Absidia Entomophtora and Basidiobolus
• sporotrichosis caused by Sporothrix schenckii.

Your doctor should not administer this medicine to you if you suffer from a common subclinical
form of fungal infection that only shows positivity to skin or serological tests.

2. What you need to know before using AmBisome

Do not use AmBisome:

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to peanuts or soy.

Warnings and precautions
Talk to your doctor or pharmacist before you are given AmBisome.
Adverse reactions affecting the kidneys have been reported and caution should be exercised in case of
prolonged therapy.

• If you are taking other medicines that can cause damage to the kidneys, see the Other medicines and AmBisomesection. AmBisome can cause damage to the kidneys. Your doctor or nurse should take blood samples to measure creatinine (a chemical in the blood that reflects kidney function) and electrolyte levels (especially potassium and magnesium) before and during treatment with AmBisome because both may be abnormal if kidney function is impaired. This is particularly important if you have previously had kidney damage or if you are taking other medicines that can affect how the kidney works. The blood samples will also be checked to detect any changes in the liver and the body's ability to produce new blood cells and platelets. If blood tests show a change in kidney function, or other significant changes, your doctor may prescribe a lower dose of AmBisome or stop treatment.
• If blood tests show that potassium levels are low.In this case, your doctor may prescribe a potassium supplement to be taken during treatment with AmBisome.
• If the blood test shows that potassium levels are high, you may experience an irregular heartbeat, sometimes severe.

Allergic reactions such as anaphylaxis and anaphylactoid reactions or of other nature have been reported following
infusion of AmBisome.
If a severe anaphylactic/anaphylactoid reaction occurs, the infusion must be immediately
stopped and the medicine will no longer be administered to you.
Cases of acute pulmonary toxicity have been reported in patients who were given amphotericin
B during or shortly after leukocyte transfusions. In this case, infusions should be administered
separately, as far apart in time as possible, and your pulmonary function should be monitored.
If you are a diabetic patient, your doctor should be aware that each vial of AmBisome contains approximately
900 mg of sucrose.

Other medicines and AmBisome
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
The concomitant administration of amphotericin B with other nephrotoxic agents (harmful to the kidneys)
(for example cyclosporine, aminoglycosides and pentamidine), in some patients, may increase the risk
of kidney toxicity caused by the drug. However, in patients who received
cyclosporine and/or aminoglycosides concurrently, AmBisome was associated with a
significantly lower nephrotoxicity compared to amphotericin B.
If your doctor gives you AmBisome with any other nephrotoxic medicine (harmful to the
kidneys), regular monitoring of kidney function is recommended.
Use with corticosteroids, ACTH (adrenocorticotropic hormone) and diuretics may worsen
hypokalemia (potassium deficiency) induced by AmBisome.
Hypokalemia caused by AmBisome may potentiate the toxicity of digitalis (medicines that support
heart function).
Hypokalemia induced by AmBisome may accentuate the curare-like effect (similar to that of
curare) of neuromuscular relaxants (e.g. tubocurarine).
Use with flucytosine (antifungal medicine) may increase the toxicity of AmBisome.
Use with antineoplastic agents (cancer medicines) may cause kidney toxicity,
bronchospasm (contraction of the airways) and hypotension (low blood pressure), and its
prescription requires a careful assessment of the risk/benefit ratio by the doctor.
The use of amphotericin B during or shortly after leukocyte transfusions may cause pulmonary toxicity.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
your doctor will need to decide whether the possible benefits outweigh the potential risks to the mother
and the baby.

Driving and using machines
Some of the side effects of AmBisome, described in section 4, may affect your ability to
drive and use machines.

AmBisome contains
AmBisome liposomal 50 mg powder for dispersion for infusion contains approximately 900 mg of sucrose
per vial. This should be taken into account if you suffer from diabetes.
Ambisome, at the maximum daily dose of 5mg/kg contains 49 mg of sodium, equivalent to 2.5%
of the maximum recommended daily intake by the WHO which corresponds to 2 g of sodium for an
adult.

3. How to use AmBisome

The doctor will decide the most suitable dosage for you.
AmBisome must be administered by intravenous infusion over a period of 30-60 minutes. For
doses higher than 5 mg/kg/day, intravenous infusion for a period of 2 hours is recommended.

Adult patients
Empirical treatment of febrile neutropenia
The recommended daily dose is 3 mg/kg.
Treatment of systemic and/or deep mycoses
The recommended dose is 3.0 mg/kg per day.
Treatment of mucormycosis
Higher dosages may be required for mucormycosis: the recommended daily dose is 5-
10 mg/kg of body weight. The duration of therapy will be defined by your doctor on an individual basis.
Treatment of cryptococcal meningitis associated with HIV
Therapy involves a single dose of AmBisome of 10 mg/kg of body weight on the first day of
treatment, as an induction phase of therapy which will be continued according to the latest
Guidelines.
Patients with renal impairment
In patients with pre-existing renal impairment, AmBisome has been administered with initial doses
ranging from 1 to 3 mg/kg/day, without the need for any dose adjustment or
frequency of administration. Regular monitoring of renal function is
recommended. There are no data on the use of AmBisome at dosages higher than 3 mg/kg per day in
patients with pre-existing renal insufficiency.
Patients with hepatic impairment
There are no data on any dosage adjustments in patients with liver impairment.
Paediatric population
In children, AmBisome is administered at doses similar to those used for adults, based on body weight.
Elderly
No modification of the dose or frequency of administration is required.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Very common (may affect more than 1 in 10 people)

• nausea
• vomiting
• common cold
• fever
• hypokalaemia (reduction of potassium levels in the blood) Common (may affect up to 1 in 10 people)
• tachycardia (accelerated heartbeat)
• vasodilation
• flushing
• hypotension (low blood pressure)
• dyspnoea (difficulty in breathing)
• diarrhoea
• abdominal pain
• abnormal liver function test
• skin rash
• back pain
• chest pain
• headache
• elevated potassium levels in the blood
• hypomagnesaemia (reduction of magnesium levels in the blood)
• hypocalcaemia (reduction of calcium levels in the blood)
• hyperglycaemia (increased blood sugar)
• hyponatraemia (reduction of sodium levels in the blood)
• hyperbilirubinaemia (high bilirubin in the blood)
• increased alkaline phosphatase
• increased creatinine
• increased blood urea Uncommon (may affect up to 1 in 100 people)
• bronchospasm (contraction of the airway muscles)
• anaphylactoid reaction (allergic reaction)
• convulsions
• thrombocytopenia (low platelets) Not known (frequency cannot be estimated from available data)
• cardiac arrest
• arrhythmia (irregular heartbeat)
• angioedema (severe allergic reaction with swelling of the face, neck, tongue, lips)
• rhabdomyolysis (severe muscle damage) associated with hypokalaemia (reduction of potassium levels in the blood)
• musculoskeletal pain
• renal function abnormalities
• renal failure
• anaemia
• anaphylactic reactions
• hypersensitivity Laboratory values
• a false elevation of serum phosphate may occur when samples taken from patients treated with AmBisome are analysed using the PHOSm test

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your
doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-

reazioni-avverse
Reporting side effects can help to provide more information on the safety of
this medicine.

5. How to store AmBisome

Keep this medicine out of the sight and reach of children.
Store sealed vials of lyophilized powder at a temperature below 25°C.
Do not use this medicine after the expiry date which is stated on the pack after “Exp.:”. The expiry
date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What AmBisome contains

• The active ingredient is liposomal amphotericin B corresponding to 50 mg of amphotericin B.
• The other ingredients are:
• sucrose
• soy lecithin (hydrogenated)
• distearoyl-lecithin
• cholesterol
• alpha tocopherol
• sodium succinate hexahydrate (sodium salt)

Description of the appearance of AmBisome and contents of the pack
Powder for dispersion for infusion in a pack containing 10 vials and 10 individual filters of
5 micron.

Marketing authorisation holder and manufacturer
Marketing authorisation holder:
Gilead Sciences S.r.l.
Via Melchiorre Gioia, 26
20124 Milan
Italy
Tel. +39 02 439201
Manufacturer:
Gilead Sciences Ireland UC
IDA Business & Technology Park
Carrigtohill, Co Cork
Ireland
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The following information is intended for healthcare professionals only:
READ THE ENTIRE PARAGRAPH CAREFULLY BEFORE PROCEEDING WITH
RECONSTITUTION

AmBisome is NOT interchangeable with other medicines containing amphotericin.
AmBisome must be reconstituted using sterile water for injections (without bacteriostatic agents) and diluted exclusively in glucose infusion solution (5%, 10%, or 20%).
Use of solutions other than those recommended, or the presence of bacteriostatic agents (e.g. benzyl alcohol) in the solution, may cause precipitation of AmBisome.
AmBisome is NOT compatible with saline solutions and must not be reconstituted or diluted with saline solutions or administered via an intravenous catheter previously used for a saline solution, unless it is first flushed with glucose infusion solution (5%, 10%, or 20%).
If this is not possible, AmBisome must be administered via a separate catheter.
Do NOT mix AmBisome with other drugs or electrolytes.
Strict aseptic technique must be followed in all operations, as no preservative or bacteriostatic agent is present in AmBisome or in the materials specified for reconstitution and dilution.
Vials of AmBisome containing 50 mg of amphotericin should be prepared as follows:
If more than one vial needs to be reconstituted, complete the entire process of reconstitution and
dispersion of one vialbefore adding sterile water to the next vial.

• 1. Add 12 ml of sterile water for injections to each vial of AmBisome to obtain a preparation containing 4 mg/ml of amphotericin B.

• 2. IMMEDIATELY after adding water, SHAKE THE VIAL VIGOROUSLY for 30 seconds to dissolve AmBisome completely. After reconstitution, the concentrate appears as a semi-transparent, yellow-colored dispersion. Visually inspect the vial for the presence of particulate matter and continue shaking until a complete dispersion is obtained. Do not use if precipitation of foreign material is present.

• 3. Calculate the amount of reconstituted AmBisome (4 mg/ml) for further dilution (see table below).

• 4. The solution for infusion is obtained by diluting reconstituted AmBisome with glucose infusion solution (5%, 10%, or 20%), from one (1) to nineteen (19) parts by volume, in order to obtain a final concentration in the recommended range of 2.0 mg/ml to 0.2 mg/ml of amphotericin as AmBisome (see table below).
• 0.2 mg/ml of amphotericin as AmBisome (see table below).
• 5. Draw up the calculated volume of reconstituted AmBisome into a sterile syringe. Using the supplied 5 micron filter, introduce the AmBisome preparation into a sterile container with the appropriate amount of glucose infusion solution (5%, 10%, or 20%).

An in-line filter may be used for the intravenous infusion of AmBisome. However, the average pore diameter of the filter must not be less than 1.0 micron.

Example of preparation of AmBisome dispersion for infusion, at a dose of 3 mg/kg, in a
5% glucose infusion solution.

Each vial of AmBisome liposomal 50 mg is reconstituted with 12 ml of water for injections,
to provide a concentration of 4 mg/ml of amphotericin B.
Unused medicine or waste material from such medicine should be disposed of in accordance with
local regulations.