• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

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

• If you are allergic (hypersensitive) to Amphotericin B or any of the other ingredients of AmBisome. However, if your condition is life-threatening you may be given AmBisome if your doctor believes that only AmBisome can help you.
• If you have previously experienced a severe allergic reaction (anaphylactic or anaphylactoid) to AmBisome. Symptoms of such immediate and life-threatening allergic reactions include: flushing, itching, sickness, swelling of the face, mouth, tongue and airways, often enough to cause difficulty breathing.

Your doctor will take special care with AmBisome

• If you have a severe allergic (anaphylactic) reaction. If this happens your doctor will stop the infusion.
• If you get other reactions related to the infusion. If this happens, your doctor may slow down the infusion, so you receive AmBisome over a longer period of time (approximately 2 hours). Your doctor may also give you medicines to prevent or treat infusion-related reactions, such as diphenhydramine (an antihistamine), paracetamol, pethidine (for pain relief) and/or hydrocortisone (an anti-inflammatory medicine that works by reducing the response of your immune system).
• If you are taking other medicines that may cause kidney damage, see section Other medicines and AmBisome. AmBisome may cause damage to the kidney. Your doctor or nurse will take blood samples. This is to test creatinine (a chemical in the blood that reflects kidney function), and electrolyte levels (particularly potassium and magnesium) before and during the treatment with AmBisome because both of these can be abnormal if you have kidney problems. This is particularly important if you have previous renal damage or if you are taking other medicines that may cause damage to the kidney. The blood samples will also be tested for changes in your liver, and your body’s ability to produce new blood cells and platelets.
• If blood tests show a change in kidney function, or other important changes. If this happens, your doctor may give you a lower dose of AmBisome or stop treatment.
• If blood tests show that your potassium levels are low. If this happens, your doctor may prescribe a potassium supplement for you to take while you are treated with AmBisome.
• If blood test shows that your potassium levels are high you may suffer irregular heartbeat, sometimes severe.
• If you have a white blood cell transfusion. Sudden and severe problems in the lungs can happen if you are given AmBisome infusion during or shortly after a white blood cell transfusion. Your doctor will recommend that the infusions are separated by as long a period as possible. This will reduce the risk of lung problems, and your lungs will be monitored.
• If you have had kidney failure and are having dialysis. Your doctor may start AmBisome treatment after the procedure has ended.
• If you have diabetes. AmBisome contains approximately 900 mg of sucrose (sugar) in each vial. Tell your doctor if you have diabetes.

Tell your doctor if you are taking any other medicines, or have recently taken any. This includes medicines and herbal products you bought without a prescription.

Medicines that may cause kidney damage:

• Medicines that suppress the immune system (immunosuppressants), such as ciclosporin and tacrolimus.
• Certain antibiotics called aminoglycosides (including gentamicin, neomycin and streptomycin) and polymixins.
• Pentamidine a medicine used to treat pneumonia in people with AIDS and leishmaniasis.

• Tell your doctor if you are taking any of these medicines. AmBisome may make any kidney damage caused by the medicine worse. If you are taking any of these medicines, your doctor or nurse will take regular blood samples to check your kidneys.

Medicines that may lower your potassium levels:

• Corticosteroids, anti-inflammation medicines that work by reducing the response of your immune system.
• Corticotropin (ACTH), used to control the amount of corticosteroid produced by your body. The body produces corticosteroid in response to stress.
• Diuretics, medicines that increase the amount of urine your body produces. This includes furosemide.
• Digitalis glycosides, medicines produced from the foxglove plant and used to treat heart failure. AmBisome may worsen the side effects of digitalis, such as heart rhythm changes.
• Muscle relaxants usually used during surgery, such as tubocurarine. AmBisome may increase the muscle relaxant effect.

Other medicines:

• Antifungal medicines, such as flucytosine. AmBisome may worsen the side effects of flucytosine. This includes changes in the body’s ability to produce new blood cells. This may be seen in blood tests.
• Certain cancer medicines, such as methotrexate, doxorubicin, carmustine and cyclophosphamide. Taking this type of medicine with AmBisome may cause kidney damage, wheezing or trouble breathing and low blood pressure.
• White blood cell (leukocyte) transfusions. Sudden and severe problems in the lungs can happen if you are given AmBisome infusion during or shortly after a white blood cell transfusion. Your doctor will recommend that the infusions are separated by as long a period as possible. This will reduce the risk of lung problems and your lungs will be monitored.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Your doctor will only prescribe AmBisome if they think the benefits of treatment outweigh the risks to you and your unborn child or your baby.

Do not drive or operate machinery

Some of the possible side effects of AmBisome could affect your ability to drive or use machines safely, See Section 4, Possible side effects.

Tell your doctor if you have diabetes. AmBisome contains approximately 900 mg of sugar (sucrose) in each vial.

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

Your dose of AmBisome will depend on your body weight.

Fungal infections of one or more deep organs of the body:

Treatment is normally started at 3 mg per kg of body weight, every day for a minimum of 14 days. The duration of therapy will be determined on an individual basis by your Doctor. Your doctor may decide to increase the amount you receive to as high as 5 mg per kg body weight.

For mucormycosis the starting dose is normally 5 to 10 mg per kg of body weight per day. The duration of therapy will be determined on an individual basis by your Doctor.

For HIV associated Cryptococcal meningitis a single dose of 10 mg/kg AmBisome, in combination with daily flucytosine 100 mg/kg and daily fluconazole 1200 mg, both administered for 14 days.

Suspected fungal infections in patients with a raised temperature and neutropenia: The recommended daily dose is 3 mg per kg of body weight, per day. Your doctor may decide to increase the amount you receive to as high as 5 mg per kg body weight. AmBisome will be given to you until your temperature is normal for 3 days in a row. However, AmBisome must not be given for more than 42 days in a row.

Visceral leishmaniasis:

You may be given a total dose of between 21 and 30 mg per kg of body weight, over a period of 10 to 21 days. Your doctor will decide on the amount of AmBisome you will receive and over how many days it will be given.

AmBisome has been used to treat children. The dose of AmBisome for a child is calculated per kg of body weight in the same way as for adults.

AmBisome is not recommended in babies under 1 month old.

No change in dose or frequency of infusion is needed for elderly patients.

AmBisome has been given to patients with kidney problems at doses ranging from 1 to 5 mg per kg of body weight per day. No change in dose or frequency of infusion is required. Your doctor or nurse will take regular blood samples to test for changes in kidney function during AmBisome treatment.

Normally the infusion will take 30 to 60 minutes. For doses greater than 5 mg per kg of body weight per day, the infusion could take up to 2 hours.

You should tell your doctor immediately if you think you received too much AmBisome. If you have any further questions on the use of this product, ask your doctor.

You may get side effects during the infusion:

• Very common (These can affect more than 1 in every 10 people): fever, chills, and shivering.
• Less frequent infusion-related side effects include: chest tightness, chest pain, breathlessness, difficulty breathing (possibly with wheezing), flushing, a faster heart rate than normal, low blood pressure and musculoskeletal pain (described as joint pain, back pain, or bone pain).

These side effects clear up quickly when the infusion is stopped. These reactions may not happen with future infusions of AmBisome or with a slower infusion (over 2 hours). Your doctor may give you other medicines to prevent infusion-related reactions, or to treat the symptoms if you do get them. If you have a severe infusion-related reaction, your doctor will stop the AmBisome infusion and you should not receive this treatment in the future.

Very common side effects

These can affect more than 1 in every 10 people:

• Low blood potassium levels, leading to feeling tired, confused, having muscle weakness or cramps
• Feeling sick or being sick
• Fever, chills or shivering.

Common side effects

These can affect up to 1 in every 10 people:

• Low magnesium, calcium or sodium blood levels, leading to feeling tired, confused, muscle weakness or cramps
• High blood sugar levels
• Headache
• A faster heart rate than normal
• Widening of the blood vessels, causing low blood pressure and flushing
• Breathlessness
• Diarrhoea
• Stomach (abdominal) pain
• Rash
• Chest pain
• Back pain
• Abnormal results for liver or kidney function showing up in blood tests or urine tests
• High blood potassium levels.

Uncommon side effects

These can affect up to 1 in every 100 people:

• Bleeding into the skin, unusual bruising and bleeding for a long time after injury
• Severe allergic (anaphylactoid) reaction
• Fits or seizures (convulsions)
• Difficulty breathing, possibly with wheezing.

It is not known how frequently these side effects occur:

• Anaemia (low red blood cell levels), with symptoms of excessive tiredness, being out of breath after light activity, and a pale complexion
• Severe allergic (anaphylactic) or sensitivity reactions
• Heart attacks and heart rhythm changes
• Kidney failure and kidney problems. Signs include tiredness and passing less urine
• Severe swelling of the skin around the lips, eyes or tongue.
• Breakdown of muscle
• Bone pain and joint pain

Interference with Phosphorus blood test results. False readings showing an increase in the levels of phosphate in your blood may occur when samples from patients receiving AmBisome are analyzed using a specific system called a PHOSm assay.

If your test results show high levels of phosphate, then further analysis using a different system may be necessary to confirm the results.

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system:

United Kingdom

Website: www.mhra.gov.uk/yellowcard

The active ingredient is amphotericin B. Each vial contains 50 mg of amphotericin B enclosed inside liposomes (small fat particles).

The other ingredients are: hydrogenated soy phosphatidylcholine, cholesterol, distearoylphosphatidylglycerol (sodium salt), alpha tocopherol, sucrose (sugar), disodium succinate hexahydrate, sodium hydroxide and hydrochloric acid.

AmBisome is a sterile, bright yellow lyophilisate (freeze-dried powder) for dispersion for infusion.

It is presented in a 15-ml, 20-ml or 30-ml glass vial.

Each vial contains 50 mg of the active ingredient amphotericin B.

The closure consists of a rubber stopper and an aluminium ring seal fitted with a removable plastic cap.

Each carton contains 10 vials and 10 filters.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Manufacturer

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