ARTESUNATE AMIVAS 110 mg POWDER AND SOLVENT FOR INJECTABLE SOLUTION

2. What you need to know before you are given Artesunato Amivas

Do not use Artesunato Amivas

• if you are allergic to artesunate, to any other antimalarial treatment containing an artemisinin (e.g. artemether or dihydroartemisinin) or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

You may develop anaemia, which is a reduction in the number of red blood cells, or other changes in the blood after treatment with this medicine. Some changes in the number of blood cells may occur during treatment for malaria which usually recover once treatment is finished. However, some individuals develop severe anaemia which can occur up to several weeks after completing treatment for malaria. In most cases, the anaemia recovers without any specific treatment. In a small number of cases, this anaemia can be severe and require blood transfusion. Your doctor will perform regular blood tests, which may include a direct antiglobulin test to determine if treatment is needed, for example with corticosteroids, and will monitor your recovery for 4 weeks after you have completed treatment for malaria. It is important that you attend these follow-up appointments. Ask your doctor for more information.

Other medicines and Artesunato Amivas

Tell your doctor if you are taking, have recently taken or might take any other medicines. This includes medicines that are not prescribed by a doctor.

Some medicines must not be taken with artesunate, as they may reduce its effect on malaria. The following are some examples:

• rifampicin (for the treatment of bacterial infections)
• ritonavir, nevirapine (anti-HIV medication)
• carbamazepine, phenytoin (for the treatment of epilepsy)

Others may increase the levels of artesunate in the blood and the risk of side effects. The following are some examples:

• diclofenac (for the treatment of pain or inflammation)

• axitinib, vandetanib and imatinib (used for the treatment of certain cancers)

Artesunate may increase or decrease the levels of other medicines in the blood. Your doctor will advise you which medicines you can take during treatment with artesunate.

Pregnancy and breast-feeding

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 explain the potential risks of taking Artesunato Amivas during pregnancy. It is not recommended during the first trimester of pregnancy unless your doctor decides that the benefits of treatment for you are greater than the risks to the foetus. In the later stages of pregnancy, you should only take Artesunato Amivas if your doctor considers that there are no suitable alternative medicines.

If you become pregnant during treatment with this medicine, your doctor will inform the manufacturer of your pregnancy, who will keep a record to understand the effects that treatment may have on pregnancy and your baby.

Traces of this medicine may appear in breast milk. It is not known if these small amounts can affect the breast-fed baby. If you are planning to breast-feed your baby, ask your doctor if the benefits of breast-feeding for you and your child are greater than the possible risks.

Driving and using machines

Do not drive or use machines if you feel tired or dizzy.

Artesunato Amivas contains sodium

This medicine contains 193 mg of sodium (main component of cooking/table salt) per single dose. This is less than 10 % of the maximum daily intake of sodium recommended for an adult.

Since the first and second doses are recommended 12 hours apart, this will be a sodium intake of 386 mg per day, which is approximately 20 % of the maximum daily intake of sodium recommended by WHO for an adult.

3. How Artesunato Amivas is given

Follow exactly the administration instructions of this medicine given by your doctor. If you are unsure, ask your doctor again.

This medicine will be given to you by slow injection directly into a vein. Your doctor or nurse will inject the medicine.

The dose of the medicine that will be given to you will be based on your weight, so your doctor or nurse will calculate the right amount. The recommended dose is 2.4 mg per kg of body weight. This dose per kg is the same for adults and children of all ages.

You will be given at least three doses of Artesunato Amivas, each 12 hours apart. After three doses, if you are still not able to take medicines by mouth, you will be given a dose of Artesunato Amivas every 24 hours (once a day) until you can take another antimalarial treatment by mouth.

It is very important that you take a full course of antimalarial treatment by mouth after you have received at least three doses of Artesunato Amivas by injection.

If you are given more Artesunato Amivas than you should

Since this medicine will be given to you in a hospital, it is unlikely that you will be given too much. Contact your doctor if you have any questions. Signs of overdose include seizures, dark stools, low blood cell counts in blood tests, weakness, fatigue, fever, and nausea. Your doctor will help you treat these symptoms if you receive too much of this medicine.

If you miss a dose of Artesunato Amivas

Since this medicine will be given to you in a hospital, your doctor or nurse will manage the treatment and it is unlikely that a dose will be missed. If a dose is delayed, your doctor or nurse will give you the dose as soon as possible and will then give you the next doses 12 or 24 hours apart.

If you have any other questions about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

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

If you experience any of the following side effects, seek medical help immediately:

• difficulty breathing or swallowing, swelling of the face, mouth or throat. These are signs that you may be having a severe allergic reaction. The frequency of very severe allergic reactions which can cause loss of consciousness is not known.

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

lack of healthy red blood cells, which can make you feel tired and weak (anaemia); this can occur at least 7 days or, in some cases, up to several weeks after finishing treatment.

Common side effects(may affect up to 1 in 10 people)

• vein inflammation
• altered sense of taste
• increased body temperature or fever
• dark yellow or brownish urine
• reduced kidney function, including reduced urine production
• easy bruising or slow bleeding from any cut or wound
• abnormal liver enzyme levels in blood tests
• yellowing of the skin (jaundice)
• diarrhoea
• abdominal pain
• vomiting
• slow heart rate
• low blood pressure
• cough
• rhinitis (blocked and/or runny nose)
• feeling dizzy or weak
• headache

Uncommon side effects(may affect less than 1 in 100 people)

• fatigue
• nausea
• constipation
• pain at the injection site
• widespread painful rash with blisters, especially near the mouth, nose, eyes and genitals, flu-like symptoms for several days (Stevens-Johnson syndrome or SJS)
• loss of appetite
• skin rash
• itching
• swelling and redness of the face
• flushing

Frequency not known(cannot be estimated from the available data)

• lack of healthy red blood cells caused by your immune system (immune haemolytic anaemia)
• abnormal heart electrical activity which affects your heart rhythm (prolonged QT interval on electrocardiogram)

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. Storage of Artesunato Amivas

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP.

This medicine does not require any special storage conditions.

The reconstituted solution must be used within 1.5 hours of preparation.

6. Contents of the pack and other information

What Artesunato Amivas contains

• The active substance is artesunate.
• Each vial of powder contains 110 mg of artesunate.
• Each vial of solvent for reconstitution contains 12 ml of sodium phosphate buffer 0.3 M.
• The other ingredients of the sodium phosphate buffer 0.3 M are monosodium phosphate monohydrate, disodium phosphate dihydrate (see section 2 ‘Artesunato Amivas contains sodium’), phosphoric acid, concentrated (for pH adjustment), sodium hydroxide (for pH adjustment) and water for injections.

After reconstitution with 11 ml of the provided solvent, the solution for injection contains 10 mg of artesunate per ml.

What Artesunato Amivas looks like and contents of the pack

Artesunato Amivas 110 mg powder and solvent for solution for injection.

The powder is a fine, white or almost white crystalline powder, contained in a glass vial.

The solvent is a clear, colourless liquid in a glass vial.

Each pack contains 2 or 4 vials of Artesunato Amivas powder and 2 or 4 vials of solvent sodium phosphate buffer.

Not all pack sizes may be marketed.

Marketing authorisation holder

Amivas Ireland Ltd, Suite 5, Second Floor, Station House, Railway Square, Waterford, Ireland

Manufacturer

MIAS Pharma Limited, Suite 1, Stafford House, Strand Road, Portmarnock, Co. Dublin, Ireland

Date of last revision of this leaflet

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu

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This information is intended only for healthcare professionals:

Preparation and administration

The required dose of Artesunato Amivas will be calculated before reconstitution:

Dose in mg = patient weight in kg x 2.4

For preparation of the dose, only the required number of vials of Artesunato Amivas will be reconstituted. Unopened vials will be stored in the pack ready for use in the next scheduled dose.

For reconstitution, withdraw 11 ml of the provided solvent (sodium phosphate buffer 0.3 M) with a needle and syringe. Inject into the vial containing the artesunate powder (final concentration of artesunate is 10 mg/ml once reconstituted). Gently swirl for 5 to 6 minutes until the powder is completely dissolved. Do not shake.

Visually inspect the solution in the vial for particulate matter and discoloration. Do not administer if the solution is discoloured or contains visible particles.

Inject the reconstituted solution of the medicine by slow intravenous bolus injection over 1-2 minutes. Do not administer by continuous intravenous infusion.

The recommended dosing regimen is at 0, 12, 24 and 48 hours and then once daily until another antimalarial medicine can be taken by mouth.

Artesunato Amivas also contains 193 mg of sodium per single recommended dose for a 60 kg adult, which is equivalent to 9.6 % of the WHO recommended maximum daily intake of 2 g of sodium for an adult. Since the first and second doses are recommended 12 hours apart, this will be a sodium intake of 386 mg per day, which is equivalent to 19.2 % of the WHO recommended maximum daily intake of 2 g of sodium for an adult.

Storage of the reconstituted solution of Artesunato Amivas

Once reconstituted, the solution of Artesunato Amivas should be administered within 1.5 hours of preparation. Discard any unused solution in accordance with local guidelines.