This Injection Guide is for the parents and caregivers of patients with paediatric-onset hypophosphatasia who would benefit from long-term enzyme replacement therapy and have been prescribed with asfotase alfa.

This guide gives detailed instructions, with clear diagrams, on how to choose the injection site and how to carry out and record the injection of your infant or child.

This guide is designed as a support document to the training given by your child's healthcare professional.

Please contact your child's healthcare professional if you have any questions.

Important Information

Do not inject your child with asfotase alfa until you have had proper training from a healthcare professional.

• Before starting, check the expiry date of asfotase alfa. DO NOT use if it has expired.
• Always use a new vial and carefully examine the liquid to make sure it is clear, colourless to slightly yellow and may have a few small translucent or white particles in it. Do not use it if the liquid is discoloured or contains any lumps or large particles in it and get a new vial.
• If you suspect that the liquid in your vial has been contaminated, DO NOT use it, select another vial and contact your child's healthcare professional for advice.
• Always use the specific dose (in number of milligrams) that has been prescribed by your child's doctor.
• Vials are for single use and should only be punctured once. Used vials must be disposed of at the end of the injection.
• Syringes and needles are for single use only and should be handled with care. Keep them out of reach from children and dispose of them safely in a special sharps container. Needles and syringes must not be mixed with normal household rubbish.
• Store your asfotase alfa vials in the refrigerator at a temperature between 2°C and 8°C. DO NOT put asfotase alfa in or near the freezer compartment and never inject asfotase alfa that you know, or suspect, has been frozen.
• Store your asfotase alfa in in the original package in order to protect the medication from light. For detailed information on asfotase alfa please refer to the Patient Information Leaflet.

Warnings and Precautions

• Some patients receiving asfotase alfa have had life threatening allergic reactions similar to anaphylaxis requiring medical treatment. Patients who experienced anaphylaxis-like symptoms had difficulty breathing, choking sensation, nausea, swelling around the eyes, and dizziness. The reactions occurred within minutes after injecting the asfotase alfa in patients, and can occur in patients who have been taking asfotase alfa for any period of time (e.g. more than one year). If your child experiences any of these symptoms, discontinue asfotase alfa and seek medical help immediately. 
• If your child experiences an anaphylactic reaction, or an event with similar symptoms, your child's doctor will discuss with you the next steps and the possibility to restart asfotase alfa under medical supervision. Always follow the instructions provided by your child's doctor.
• Fatty lumps or decreased fatty tissue on the surface of the skin (localised lipodystrophy) has been reported at injection sites after several months in patients using asfotase alfa. Review the 'How is asfotase alfa Administered?' section carefully to know the injection recommendations. It is important to rotate the injection from among the following sites to reduce the risk of lipodystoprhy: buttocks, abdomen, thigh or arms (deltoids). 
• If your child is treated with asfotase alfa, they may experience a reaction at the injection site (e.g. pain, nodule, rash or discolouration) during the injection of the medicine or during the hours following the injection. If you observe any severe reaction at the injection site, tell your child's doctor immediately. 

What is asfotase alfa?

Asfotase alfa is a medication designed as a long-term enzyme replacement therapy in patients with paediatric-onset hypophosphatasia. It is administered subcutaneously (under the skin). 

How does my infant or child get started on asfotase alfa therapy?

Asfotase alfa must be prescribed by your infant or child's doctor. Your child's healthcare professional will advise you on the range of educational materials available to help with the therapy. This injection guide can help support you when learning how to inject your infant or child.

What dose of asfotase alfa is used?

Once asfotase alfa has been prescribed for your infant or child  you will need to administer the drug according to the specific dose (in number of milligrams) that has been prescribed by your doctor.

The dose you administer is based on your infant or child's body weight. The correct dose will be calculated by your doctor and consists of a total of 6mg per kg of body weight per week of asfotase alfa, administered by subcutaneous injection. Your child may receive either an injection of 1mg/kg of asfotase alfa six times per week or an injection of 2mg/kg of asfotase alfa three times per week depending on the recommendation of your doctor.

For example, if the body weight of your infant or child is 6kg, they will receive 6mg six times per week or 12mg three times per week. The maximum volume of medication per injection should not exceed 1ml. If more than 1ml is required, multiple injections may be administered, one after another.

How is asfotase alfa administered?

Asfotase alfa is administered either three or six times per week as a subcutaneous injection into the fatty layer just below the skin. This is called the subcutaneous layer and is just above the muscle. 

There are specific areas of the body suitable for giving subcutaneous injections to infants and children, shown on the diagram below. As a general rule, these areas are those wit ha substantial amount of fat below the skin. The thighs and abdomen tend to be the most suitable for infants and children.

When injecting regularly, it is important to alternate injection sites (position on the body where the injections are given) to limit risk of pain, irritation and lipodystrophy (clumping or loss of fat under the skin). 

As your infant or child grows, other areas may become suitable, such as the arms and buttocks. Please discuss with your child's healthcare professional the best sites for your infant or child.

Please remember, this guide is designed as a support document to the training given by your child's healthcare professional.

How to Inject asfotase alfa

Before you begin, take your vial(s) out of the refrigerator 15 to 30 minutes before injecting to allow the liquid to reach room temperature (around 23°C to 27°C). Do not warm asfotase alfa in any other way (for example, do not warm it in a microwave or in hot water). After removal of the vial from refrigeration, asfotase alfa should be administered within 3 hours. There is more information about the storage of asfotase alfa at the end of this article.

Please remember your vials are for single use and should only be punctured once. Used vials must be disposed of at the end of the injection.

Place all the items you will need on a clean area where they will not be disturbed. These should include:

• Your child's vial(s) for injection.
• Your child's syringe(s).
• One larger bore syringe needle (e.g. 25G).
• One smaller bore syringe needle (e.g. 27G or 29G, with length appropriate for subcutaneous injection).
• Alcohol swabs (if required).
• Gauze or cotton wool.
• A sharps container.
• Plaster or adhesive bandage (if required).
• Injection diary (or other recording means e.g. paper or notebook).

It is recommended to record site, dose, date and time, to avoid two injections in the same day and to ensure you rotate injection site. It is also recommended to note any injection reactions. Choose the injection site (see diagram below) and prepare it according to the advice given by your child's healthcare professional.

1. Preparing the asfotase alfa dose

1.1 Always use a new vial and carefully examine the liquid to make sure it is clear, colourless to slightly yellow, and may have a few small translucent or white particles in it. Do not use it if the liquid is discoloured or contains any lumps or large particles in it and get a new vial.

Remove the protective cap from the vial to reveal the sterile rubber seal.

1.2 Place a larger bore needle (e.g. 25G) on the empty syringe and with the protective cap on, push down and turn clockwise the needle onto the syringe until it is tight. Remove the plastic cap covering the syringe needle and dispose of it in the sharps container. Pay attention to not hurt yourself with the needle.

Pull the plunger back to draw air into the syringe equal to the correct dose.

2. Withdrawing asfotase alfa solution from the vial

2.1  Holding the syringe and vial insert the needle through the sterile rubber seal and into the vial. Push the plunger in completely to inject the air into the vial.

2.2 Invert the vial and syringe. With the needle in the solution, pull the plunger to withdraw the correct dose into the syringe.

2.3 Before removing the needle from the vial, check that the appropriate volume has been withdrawn and check the syringe for air bubbles.

In the even that bubbles appear in the syringe, hold the syringe with the needle pointing upwards and gently tap the side of the syringe until the bubbles rise to the top. 

2.4 Once all the bubbles are at the top of the syringe, gently push on the plunger to force the bubbles out of the syringe and back into the vial.

After removing the bubbles, recheck the dose of medication in the syringe to be sure you have drawn up the correct amount. You may need to use several vials to withdraw the complete amount needed to reach the correct dose.

3. Placing the needle for injection on the syringe

3.1 Remove the needle from the vial. Recap with one hand by placing the cap on a flat surface, slide the needle into the cap, lift it up and snap it on securely using only one hand.

3.2 Carefully remove the recapped larger bore needle pushing down and turning anticlockwise and dispose of it in the sharps container.

3.3 Place a smaller bore needle (e.g. 27G or 29G) on the filled syringe and with the protective cap on, push down and turn clockwise the needle onto the syringe until it is tight. Pull the cap straight off the needle and dispose of it in the sharps container.

3.4 Hold the syringe with the needle pointing up and tap the barrel of the syringe with your finger to remove any air bubbles. After removing the bubbles, recheck the dose of medication in the syringe to be sure you have drawn up the correct amount. You are now ready to inject the correct dose.

4. Injecting asfotase alfa

Please refer to Section 'How asfotase alfa is administered' for determining the most suitable injection site on your infant or child (thigs, abdomen, arms (deltoids), buttocks). 

4.1 Hold your infant or child firmly in a comfortable position. Your child's healthcare professional will advise you on the best position to hold your infant or child for the chosen injection site.

4.2 Gently pinch the skin of the chosen injection area (in this case the infant or child's thigh) between your thumb and index finger.

4.3 Holding the syringe like a pencil or a dart, insert the needle into the raised skin so it is at an angle of between 45° and 90° to the skin surface.

For small children who have little subcutaneous fat or thin skin, a 45° angle may be preferable.

4.4 While continuing to hold the skin, push the syringe plunger to inject the medication slowly and steadily all the way in. 

Remove the needle, release the skin fold, place the syringe in the sharps container, and gently place a piece of cotton wool or gauze over the injection site for a few seconds. This will help seal the punctured tissue and prevent any leakage. Do not rub the injection site after injection.

4.5 Dispose of your syringe, used vial and needle into the sharps container. Your child's doctor, pharmacist or nurse will advise you on how you can obtain a sharps container.

4.6 If you need a second injection for your child's prescribed dose, get another asfotase alfa vial and new needles, then repeat all of the previous steps.

The vials are for single use and should only be punctured once.

Place a small plaster or adhesive bandage over the injection site, if necessary.

4.7 Record all details of the injection in the injection diary or using other means. It is recommended that you note:

• where you injected
• the dose injected
• date and time of injection
• any injection reactions

If you have any concerns about injection reactions, preparing or administering your medication, discuss them with your child's doctor, pharmacist or nurse.

Storing and travelling with asfotase alfa

Storing child's asfotase alfa vials:

• Store your child's asfotase alfa vials in the refrigerator at a temperature between 2°C and 8°C. DO NOT put asfotase alfa in or near the freezer compartment and never inject asfotase alfa that you know, or suspect, has been frozen.
• Store your child's asfotase afla in the orignal package in order to protect the medication from light.
• Before starting, check the expiry date of asfotase alfa which you will find on the vial label. DO NOT use if it has expired.

Travelling with your child's asfotase alfa vials:

• Calculate how many vials your child will need for your trip. Take some extra in case you are away for longer than expected.
• Remember to take the sharps container and some extra syringes. It is recommended that you carry your child's supplies as hand luggage.
• Check to ensure that your travel destination has refrigeration that you can use.
• It is recommended that you carry your child's vials in a cool bag when you travel. The bag should contain cool blocks to help keep your vials at the correct temperature.
• Keep the cool blocks in your freezer so that they are ready for use when you travel. Ensure that the frozen cool blocks are not in direct onctact with your child's medication.

Travelling by air:

• It is recommended that you carry your child's medication and supplies as hand luggage.
• It may be advisable to carry a letter from your infant or child's doctor explaining that you need to travel with their medication.
• Check with your airline, or the airports you are travelling through, for any specific rules for persons carrying injectable medication and associated accessories.
• If you have any concerns about travelling, discuss them with your child's healthcare professional.
  

References

Injection Guide https://www.medicines.org.uk/emc/rmm/320/Document