Patient leaflet - Alofisel 5 x 106 Cells/ml Dispersion for injection
1. What Alofisel is and what it is used for
The active ingredient of Alofisel is darvadstrocel which consists of stem cells which are taken from the fat tissue of a healthy adult donor (so-called allogenic stem cells) and then grown in a laboratory. Adult stem cells are a special type of cells found in many adult tissues, whose primary role is the repair of the tissue in which they are found.
Alofisel is a medicine used for the treatment of complex perianal fistulas in adult patients with Crohn´s disease (a disease causing inflammation of the gut) when the other symptoms of the disease are controlled or have a mild intensity. Perianal fistulas are abnormal channels that connect parts of the lower bowel (rectum and anus) and the skin near the anus, so that one or more openings appear near the anus. Perianal fistulas are described as complex if they have multiple channels and openings, if they penetrate deep inside your body or if they are associated with other complications such as collections of pus (infected liquid also called abscesses). Perianal fistulas can cause pain, irritation and discharge of pus through the openings to the skin.
Alofisel is used when the fistulas have not responded sufficiently well to previous treatment. When injected close to the perianal fistulas, Alofisel reduces their inflammation, increasing the likelihood of the fistulas healing.
2. What you need to know before you are given Alofisel
You must not be given Alofisel
if you are allergic to darvadstrocel, bovine serum or to any of the
ingredients of this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor or surgeon before you are given Alofisel.
Alofisel may contain traces of either gentamicin or benzylpenicillin and streptomycin (antibiotics). This should be considered if you are allergic to these antibiotics, as these antibiotics are used in the manufacturing process of this medicine.
Alofisel is a living cell therapy and, therefore, the final product cannot be sterilised. The product is checked at different stages during its manufacture to ensure that it is free of infection. Because the final check takes place just before Alofisel is sent to the hospital, the results of this last check are not known when it is given to you. In the unlikely event that the results detected an infection, your treatment team will be informed who will tell you if you need any laboratory tests of treatment for the infection. If after the procedure you feel ill or have fever, please inform your physician as soon as you can.
Before receiving Alofisel you will undergo the preparation of your fistulas. You may experience pain in the rectum or anus, and pain occurring after fistula preparation.
After you receive Alofisel do not donate blood, organs, tissues or cells for transplants.
Children and adolescents
This medicine should not be given to children and adolescents below 18 years of age. It is not known if this medicine is safe and effective when used in children and adolescents under 18 years of age.
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/surgeon for advice before you are given this medicine. Treatment with Alofisel is not recommended during pregnancy. Women of childbearing age should use effective contraception during treatment with Alofisel.
The effect of Alofisel on breast-feeding women is not known, and it may harm your breast-fed child. Your doctor will help you decide whether to stop breast-feeding, or whether to stop taking Alofisel, considering the benefit of breast-feeding to the baby and the benefit of Alofisel to the mother.
Driving and using machines
Alofisel is not likely to affect your ability to drive or use tools or machines.
3. How Alofisel is given
Alofisel will always be given to you by a healthcare professional.
You may have had an initial consultation with the Surgeon 2 to 3 weeks prior to Alofisel administration. The following information is related to the day when Alofisel is administered.
Alofisel is injected by a surgeon in the fistula tract tissue.
The recommended dose is 4 vials of 6 mL (120 × 106 cells).
Before treatment with Alofisel, you will be given an anaesthetic.
Once you have been anaesthetised (general or regional anaesthesia), your surgeon will:
prepare the fistulas with sodium chloride 9 mg/mL (0.9%) solution and
remove any scar tissue.
- stitch up the inner openings of the fistulas.
inject Alofisel. Half of the dose will be injected into the tissue around the
inner openings of the fistulas, and half of the dose in the tissue walls along the fistulas.
massage softly for 20 to 30 seconds the area where the fistula opens on
to the skin near your anus.
If you have any further questions on the use of this medicine, ask your doctor or surgeon.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects of Alofisel treatment are related to the preparation of your fistulas. In general, these side effects are quite mild and disappear in the days following the fistula procedure. These side effects may occur up to seven days after the procedure.
Common side effects (may affect up to 1 to 10 patients):
- anal abscess
- anal fistula
- proctalgia (pain in the rectum or anus).
procedural pain (pain after fistula preparation)
Reporting of side effects
If you get any side effects talk to your doctor. This includes any side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.
5. How to store Alofisel
The following information is intended for doctors only.
Do not use this medicine after the expiry date which is stated on the label and the carton.
Store between 15°C and 25°C.
Do not refrigerate or freeze.
Keep the medicine inside the cardboard box to protect from light and moisture, and within the shipping container at all times until its administration, to maintain the required temperature.
Alofisel must not be irradiated or otherwise sterilised.
6. Contents of the pack and other information
What Alofisel contains
- The active ingredient is darvadstrocel which consists of human stem cells obtained from the fat tissue of a healthy adult donor that are subsequently grown (expanded) in the laboratory and provided at a concentration of 5 × 106 cells per millilitre in vials which each contain 6 millilitres, i.e. 30 × 106 cells per vial.
There are two excipients used for storage of the cells: one is a liquid called
Dulbecco’s Modified Eagle´s Medium containing nutrients for the cells (amino acids, vitamins, salts and carbohydrates), and the other is human albumin, which is a natural protein found in the human body.
What Alofisel looks like and contents of the pack
Alofisel is a suspension for injection. During shipment, the cells may have settled in the bottom of the vials forming a sediment and will need to be resuspended. After the cells have been resuspended (by gentle manual tapping), Alofisel is a white to yellowish homogenous suspension.
Alofisel is supplied on an individual patient basis. An individual dose of Alofisel comprises 4 glass vials each containing 6 millilitres of Alofisel contained within a cardboard box.
Marketing Authorisation Holder
Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark
Manufacturer
Takeda Ireland Ltd.
Grange Castle Business Park
Dublin 22, D22 XR57
Ireland
This leaflet was last revised in 09/2023
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The following information is intended for healthcare professionals only:
Traceability
The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability the name of the product, the batch number and the name of the treated patient must be kept for a period of 30 years after the expiry date of the product.
Preparation prior to administration
Alofisel must not be filtered or administered using a needle thinner than 22G. Immediately before use, Alofisel must be re-suspended by gently tapping the bottom of the vial until a homogeneous suspension is obtained, avoiding bubble formation.
Administration
Immediately prior to the administration of Alofisel, the fistula tracts should be conditioned as follows:
- a) If setons are in place, they must be removed.
- b) Identify the location of the internal openings. For this, injection of a sodium chloride 9 mg/mL (0.9%) solution through the external openings until it gets out through the internal openings is recommended. The injection of any other substance through the fistula tracts, such as hydrogen peroxide, methylene blue, iodine solutions or hypertonic glucose solutions is not allowed, as these agents compromise the viability of the cells to be injected (see section 4.4 and section 4.5).
- c) Perform a vigorous curettage of all fistula tracts, with special emphasis in the internal openings areas, using a metallic curette.
- d) Suture closed the internal openings.
After conditioning of the fistula tracts, Alofisel should be administered according to the following two steps:
- 1.
Preparation
- a) The expiry time: date of Alofisel should be re-confirmed; vials should then be removed from the outer packaging.
- b) Re-suspend the cells by gently tapping the bottom of the vials until a homogeneous suspension is obtained, avoiding bubble formation. Each vial should be used immediately after re-suspension to prevent the cells from re-sedimenting.
- c) Remove the cap from the vial, gently turn the vial upside down, and gently aspirate the whole content using a syringe with a conventional needle no thinner than 22G (see section 4.4).
- d) Replace the needle with a longer needle, also no thinner than 22G, in order to reach the intended sites of injection. For example, a needle for spinal anaesthesia measuring around 90 mm in length is required.
- e) Repeat steps (b), (c) and (d) for each of the vials in turn after the cells from one vial have been injected.
- 2.
Injection
Two of the vials should be used for the internal openings and the remaining two for injection along the walls of the fistula tracts (via external openings). After inserting the needle tip into each intended injection site, perform a slight aspiration to avoid intravascular administration.
- a) Injection around the internal openings of the fistula tracts: insert the needle through the anus and proceed as follows:
- - If there is a single internal opening, inject the content of each of the two vials (one after the other) in small deposits into the tissue surrounding the single internal opening.
- - If there are two internal openings, inject the content of the first of two vials in small deposits into the tissue around one internal opening. Then inject the content of the second vial in small deposits into the tissue around the second internal opening.
- b) Injection along the walls of the fistula tracts: insert the needle through the external openings and, from within the fistula lumen:
- - If there is a single external opening, inject separately the content of each of the remaining two vials superficially into the tissue walls along the length of the fistula tracts, making small deposits of the cell suspension.
- - If there are two or three external openings, inject the content of the remaining two vials equally between the associated tracts. The procedure for injection along the walls of the fistula tracts should be performed based on prior knowledge of the anatomy and topology of the fistula tracts, as determined during the fistula characterisation. Ensure cells are not injected into the lumen of the fistula tracts to avoid leakage of cells.
Softly massage the area around the external openings for
20–30 seconds and cover the external openings with a sterile bandage.
Precautions to be taken for the disposal of the medicinal product Unused medicinal product and all material that has been in contact with Alofisel (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling of human-derived material.