Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Mepsevii 2 mg/mL concentrate for solution for infusion
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Vestronidase alfa may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
What Mepsevii is Mepsevii contains an enzyme called vestronidase alfa. This belongs to a group of medicines called enzyme replacement therapies. It is used in adults and children of all ages with MPS VII to treat nonneurological manifestations of the disease (mucopolysaccharidosis VII, also known as Sly Syndrome). What is MPS VII MPS VII is an illness that runs in families, where the body does not produce enough of an enzyme called beta-glucuronidase. This enzyme helps to break down sugars in the body called mucopolysaccharides. Mucopolysaccharides are made in the body and they help build bones, cartilage, skin, and tendons. These sugars are re-cycled all the time – new ones are made and old ones are broken down. Without enough beta-glucuronidase, parts of these sugars build up in cells, leading to damage in the body. How Mepsevii works This medicine replaces beta-glucuronidase – this helps to break down the sugars that collect in the tissues of people with MPS VII. Treatment may improve various signs and symptoms of illness, like walking difficulties and tiredness. Starting treatment early in children may stop the illness getting worse and reduce permanent damage.
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What you need to know before you take it
Mepsevii
You must not be given Mepsevii If you have ever had a severe allergic reaction to vestronidase alfa or any of the other ingredients of this medicine (listed in section 6). Warnings and precautions Talk to your doctor before you are given Mepsevii. The effects of treatment with vestronidase alfa should be periodically evaluated and discontinuation of treatment should be considered in cases where clear benefits (including stabilisation of disease manifestations) are not observed. Discontinuation of treatment may cause significant worsening of clinical status. It should be considered that the administration of vestronidase alfa does not affect the irreversible complications (e.g. skeletal deformities). Look out for side effects during or shortly after Mepsevii infusion –
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You may have side effects while you are being given Mepsevii or for up to a day afterwards. These side effects are called infusion reactions because they are caused by the infusion (drip) of the medicine. They may include an allergic reaction (see section 4). If you have an infusion reaction, tell your doctor straight away. If you have an allergic reaction during your infusion your doctor may slow down, or stop your infusion. Your doctor may also give (or have given) you other medicines to manage the allergic reaction such as an antihistamine or corticosteroid or an antipyretic, a medicine to reduce fever.
Other symptoms to look out for –
If you have neck or back pain, feel numb in your arms or legs, or experience lack of control over passing water (urine) or stools, tell your doctor straight away. These problems can be signs of the illness and may be caused by pressure on your spinal cord.
Other medicines and Mepsevii Tell your doctor if you are using, have recently used or might use any other medicines. 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 using this medicine. You will not be given Mepsevii if you are pregnant unless treatment is clearly necessary. Discuss with your doctor if the benefits of using Mepsevii are greater than the possible risks to your unborn baby. This is because there is no experience on the use of Mepsevii during pregnancy. It is not known whether Mepsevii passes into breast milk, but transfer of the medication to your baby is not expected. Discuss with your doctor if the benefits of using Mepsevii are greater than the potential risk to your baby while breast-feeding. Driving and using machines Mepsevii is not likely to affect you being able to drive or use machines. Mepsevii contains sodium This medicine contains 17.8 mg sodium (main component of cooking/table salt) in each 5-mL vial, and is administered with sodium chloride 9 mg/mL as a diluent. Each vial dosed is therefore equivalent to 1.8% of the recommended maximum daily dietary intake of sodium for an adult. Take this into account if you are on a controlled sodium diet.
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How to take it
Treatment with Mepsevii should be started and monitored by your doctor. Your doctor or nurse will give Mepsevii to you by an infusion (drip) into a vein. The medicine has to be diluted before being given. Your doctor may give (or have given) you some medicines to manage the allergic reaction such as an antihistamine or corticosteroid or an antipyretic, a medicine to reduce fever. Dose The dose you will receive is based on how much you weigh. The recommended dose is 4 mg for each kg of body weight. The dose is given every two weeks through a drip into a vein (intra-venous infusion). Each infusion will be given over about 4 hours. If you are given more Mepsevii than you should Mepsevii is given to you and monitored by your doctor. He or she will check that the correct dose has been given and take action as needed. If you have any further questions on the use of this medicine, ask your doctor.
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Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Possible side effects
were mainly seen while patients were being given the medicine or within a day after the infusion (infusion reactions). Serious side effects Severe allergic reaction (Very common: may affect more than 1 in 10 people): Tell your doctor or nurse immediately if you get any of the following symptoms of a severe allergic reaction (anaphylactoid reaction). The infusion will be stopped immediately and your doctor may give (or have given) you other medicines to manage the allergic reaction such as an antihistamine or corticosteroid or an antipyretic, a medicine to reduce fever. Symptoms of severe allergic reaction may include shortness of breath, wheezing, difficulty breathing, and swelling of the face and tongue. Other side effects Tell your doctor straight away if you notice any of the following side effects – you may need urgent medical treatment: Very common side effects (may affect more than 1 in 10 people): Hives (urticaria) Rash Swelling at the infusion site including leaking into the tissue around the vein (infusion site swelling or infusion site extravasation) Common side effects (may affect up to 1 in 10 people): Itching of the skin (pruritus) Loose stools (diarrhoea) Fever with involuntary contractions of muscles of face or limbs (febrile convulsion) Swelling around the infusion site Reporting of side effects 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: Yellow Card Scheme
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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.
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How to store it
Mepsevii
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'. The expiry date refers to the last day of that month. Unopened vials: Store in a refrigerator (2 °C to 8 °C). Do not freeze. Store in the original package in order to protect from light. Do not use this medicine if you notice particles. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
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Contents of the pack and other information
What Mepsevii contains The active substance is vestronidase alfa. Each mL of concentrate contains 2 mg vestronidase alfa. Each vial of 5 mL concentrate contains 10 mg vestronidase alfa. –
The other ingredients are: sodium dihydrogen phosphate dihydrate, sodium chloride, histidine, polysorbate 20, and water for injections (for sodium, see section 2 under "Mepsevii contains sodium").
What Mepsevii looks like and contents of the pack Mepsevii is supplied as a concentrate for solution for infusion (sterile concentrate). The colourless to slightly yellow concentrate must be free of visible particles. It is supplied in a clear glass vial with a rubber stopper and an aluminium seal with a plastic cap. Pack size: 1 vial of 5 mL Marketing Authorisation Holder Ultragenyx Germany GmbH Rahel-Hirsch-Str. 10 10557 Berlin Germany Manufacturer Ultragenyx Netherlands B. V. Evert van de Beekstraat 1, Unit 104 1118 CL Schiphol The Netherlands Millmount Healthcare Ltd. Block-7, City North Business Campus Stamullen, Co. Meath, Ireland For any information about this medicine, please contact the local representative of the Marketing 4
Authorisation Holder: Ultragenyx Germany GmbH, DE Tel : + 49 30 20179810
This leaflet was last revised in July 2023 This medicine has been authorised under 'exceptional circumstances'. This means that because of the rarity of this disease, it has been impossible to get complete information on this medicine. The European Medicines Agency will review any new information on this medicine every year and this leaflet will be updated as necessary. Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.
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Frequently asked questions about Mepsevii 2 mg/mL concentrate for solution for infusion
How do I take Mepsevii 2 mg/mL concentrate for solution for infusion?
Mepsevii 2 mg/mL concentrate for solution for infusion comes as infusion containing 2mg/ml. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Mepsevii 2 mg/mL concentrate for solution for infusion?
The active substance in Mepsevii 2 mg/mL concentrate for solution for infusion is vestronidase alfa.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Mepsevii 2 mg/mL concentrate for solution for infusion, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get Mepsevii 2 mg/mL concentrate for solution for infusion without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: vestronidase alfa
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Mepsevii is indicated for the treatment of non-neurological manifestations of Mucopolysaccharidosis VII (MPS VII; Sly syndrome).
4.2. Posology and method of administration
Treatment should be supervised by a healthcare professional experienced in the management of patients with MPS VII or other inherited metabolic disorders. Administration of vestronidase alfa should be carried out by an appropriately trained healthcare professional with the ability to manage medical emergencies.
Posology
The recommended dose of vestronidase alfa is 4 mg/kg of body weight administered by intravenous infusion every two weeks.
To minimise the risk of hypersensitivity reactions, a non-sedating antihistamine with or without an antipyretic medicinal product should be administered 30-60 minutes prior to the start of the infusion (see section 4.4). Infusion should be avoided if the patient has an acute febrile or respiratory illness at the time.
Special populations
Elderly
The safety and efficacy of vestronidase alfa in patients older than 65 years have not been established. No alternative dose regimen is recommended in these patients (see section 5.1).
Renal and hepatic impairment
The safety and efficacy of vestronidase alfa in patients with renal or hepatic impairment have not been evaluated. No alternative dose regimen is recommended in these patients.
Paediatric population
The posology in the paediatric population is the same as in adults. Currently available data are described in section 4.8 and section 5.1.
Method of administration
For intravenous use only.
For instructions on dilution of the medicinal product before administration, see section 6.6.
The total diluted volume of the solution for infusion should be administered with a rate titration regimen over approximately 4 hours.
The rate of infusion should be as follows: in the first hour, 2.5% of the total volume will be infused, with the balance infused over the subsequent three hours. Any dead space in the lines should be accounted for to ensure 2.5% of the total infusion volume is delivered into the patient's bloodstream during the first hour of infusion. The lowest rate administered to a patient in the clinical development program was 0.5 mL/hour during the first 30 minutes of infusion, followed by 1 mL/hour over the next 30 minutes, equalling 0.75 mL as the lowest total volume infused during the first hour.
Do not flush the line containing vestronidase alfa to avoid a rapid bolus of infused enzyme. Due to the low infusion rate, additional sodium chloride 9 mg/mL (0.9%) solution for infusion may be added through a separate line (piggyback or Y tube) to maintain sufficient intravenous flow. After the first hour, the rate can be increased to infuse the remainder of the solution for infusion over 3 hours as tolerated according to the recommended rate guidelines in Table 2.
The infusion rate may be slowed, temporarily interrupted or discontinued in the event of hypersensitivity reactions (see section 4.4).
4.3. Contraindications
Life-threatening hypersensitivity (anaphylactic reaction) to the active substance or to any of the excipients listed in section 6.1 (see section 4.4).
4.4. Special warnings and precautions for use
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
General
The effects of treatment with vestronidase alfa should be periodically evaluated and discontinuation of treatment should be considered in cases where clear benefits (including stabilisation of disease manifestations) are not observed. Discontinuation of treatment may cause significant worsening of the patient's clinical status.
As end organ damage progresses over time, it is more difficult for the treatment to reverse the damage or to show improvements. It should be considered by the treating physician that the administration of vestronidase alfa does not affect the irreversible complications (e.g. skeletal deformities).
Vestronidase alfa, at the exposure observed in humans, is not expected to cross the blood-brain-barrier and therefore it is not likely to impact the neurological manifestations of the disease.
Hypersensitivity reactions including anaphylaxis
Serious hypersensitivity reactions, including anaphylaxis, have been reported with vestronidase alfa; therefore, appropriate medical support should be readily available when vestronidase alfa is administered (see section 4.8).
Infusion should be avoided if the patient has an acute febrile or respiratory illness at the time.
It is recommended that premedication with non-sedating antihistamines with or without antipyretics be administered 30-60 minutes prior to the start of the infusion (see section 4.2).
It is important to administer vestronidase alfa according to the recommended infusion rate schedule (see Table 2 in section 6.6).
If severe hypersensitivity reactions occur, the infusion of vestronidase alfa should be stopped immediately and appropriate treatment should be initiated. Management of hypersensitivity reactions should be based on the severity of the reaction and include temporary interruption or discontinuation of the infusion and/or administration of additional antihistamines, antipyretics, and/or corticosteroids for mild to moderate reactions. Consider rapid sodium chloride 9 mg/mL (0.9%) solution for infusion for decreased blood pressure and oxygen for hypoxia. Patients should be observed for a minimum of 60 minutes after completing the infusion of vestronidase alfa.
Patients should be informed of the signs and symptoms of hypersensitivity reactions and instructed to seek immediate medical care should such signs and symptoms occur. The risks and benefits of re-administering vestronidase alfa should be considered following a severe hypersensitivity reaction.
Spinal/cervical cord compression
Spinal or cervical cord compression is a known and serious complication of MPS VII. During enzyme replacement therapy, spinal cord injury can occur due to improved neck and spine mobility. Patients with MPS VII receiving vestronidase alfa should be monitored for signs and symptoms of spinal cord compression or neck instability including neck or back pain, weakness of limbs, changes in reflexes or urinary and faecal incontinence. Appropriate clinical treatment should be immediately sought.
Sodium restricted diet
This medicinal product contains 17.8 mg sodium per vial and is administered in sodium chloride 9 mg/mL (0.9%) solution for infusion (see section 6.6). For each vial dosed, including the corresponding diluent volume, the sodium intake is 35.5 mg sodium. This amount is equivalent to 1.8% of the WHO recommended maximum daily intake of 2 g for sodium for an adult. Mepsevii is considered high in sodium. This should be taken into consideration during dilution of the medicinal product for patients on a controlled sodium diet or for those patients with congestive heart failure needing to restrict sodium and total water intake.
4.5. Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed. Because it is a recombinant human protein and its enzyme action is within the lysosome, vestronidase alfa is not expected to interact with other medicinal products.
4.6. Fertility, pregnancy and lactation
Pregnancy
There are no data on the use of vetronidase alfa in pregnant women. Animal studies with vestronidase alfa do not indicate direct or indirect harmful effects with respect to pregnancy, embryo-foetal development, or pre- and postnatal development (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of Mepsevii during pregnancy, unless the potential benefit to the mother outweighs the potential theoretical risks to the foetus.
Breast-feeding
There are no data from studies in breast-feeding women. It is not known whether vestronidase alfa is excreted in human milk, but systemic exposure via breast-milk is not expected. Due to lack of human data, vestronidase alfa should only be administered to a breast-feeding woman if the potential benefit of vestronidase alfa to the mother and the benefit of breast-feeding to the infant outweighs the potential theoretical risks to the infant.
Fertility
No human data are available on the effect of vestronidase alfa on fertility. Animal studies with vestronidase alfa do not indicate any impact on male or female fertility (see section 5.3).
4.7. Effects on ability to drive and use machines
Mepsevii has no or negligible influence on the ability to drive and use machines.
4.8. Undesirable effects
Summary of the safety profile
The most common adverse reactions from 4 clinical trials in 23 patients treated with vestronidase alfa were rash (17.4%), urticaria (17.4%), infusion site extravasation (17.4%), anaphylactoid reaction (13%), infusion site swelling (8.7%), pruritus (8.7%) and diarrhoea (8.7%). Most adverse reactions were mild to moderate in severity.
Tabulated list of adverse reactions
The assessment of adverse reactions was based on the exposure of 23 patients from 4 clinical trials, aged 5 months to 25 years, who received vestronidase alfa at doses up to 4 mg/kg once every two weeks for up to 187 weeks. Nineteen patients were younger than 18 years of age.
Table 1 lists the adverse reactions reported from 4 clinical trials in 23 patients treated with Mepsevii. Adverse reactions are presented by System Organ Class and frequency. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), and very rare (< 1/10 000).
Table 1 Adverse reactions reported in patients treated with Mepsevii
MedDRA System Organ Class
MedDRA Preferred Term (PT)
Frequency
Immune system disorders
Anaphylactoid reaction
Very common
Nervous system disorders
Febrile convulsion*
Common
Gastrointestinal disorders
Diarrhoea
Common
Skin and subcutaneous tissue disorders
Urticaria
Rash**
Pruritus
Very common
Very common
Common
General disorders and administration site conditions
Infusion site extravasation***
Infusion site swelling****
Very common
Common
*Refer to description of selected adverse reactions for details on the febrile convulsion reported in 1 of 23 trial patients.
** Rash includes grouped PTs of rash, rash papular, rash pruritic, rash maculo-papular, papule, and macule
*** Infusion site extravasation includes one PT of extravasation
**** One adverse reaction of Peripheral swelling is included within the frequency of Infusion site swelling as the event is classified as intravenous catheter issue.
Description of selected adverse reactions
Febrile convulsion
One patient receiving a vestronidase alfa dose of 4 mg/kg experienced a febrile convulsion during treatment at the week 66, within 3 days of diphtheria, tetanus, pertussis vaccination. The infusion was stopped, the patient received anticonvulsants, antipyretics and antibiotics, and the febrile convulsion resolved. The patient subsequently was re-challenged without recurrence and continued on vestronidase alfa treatment. This event was assessed as possibly related to vestronidase alfa due to the temporal association with the infusion.
Immunogenicity
Eighteen out of 23 patients (78%) from 4 clinical trials developed anti-recombinant human beta-glucuronidase (rhGUS) antibodies (ADA), ten of whom further developed neutralizing antibodies (NAb) on at least one occasion, but not consistently over time. There is no definitive correlation between the antibody titre and neutralizing antibody development. In most patients, a pattern of attenuated immunogenicity with chronic exposure was suggested by declining antibody titres over time on continuous treatment. The presence of ADA (non-NAb and NAb) does not appear to affect reduction in the pharmacodynamic marker, urinary glycosaminoglycans (uGAGs) and development of hypersensitivity reactions including infusion associated reactions.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
There is no experience with overdoses of vestronidase alfa. For the management of adverse reactions, see sections 4.4 and 4.8.
🇷🇴 Known in Romania as
Medicines sold in Romania with the same active substance: Cunoscut în România ca
- MEPSEVII 2 mg/ml prescriptionVESTRONIDASUM ALFA · injection / infusion
Same active substance. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Romanian medicines in the UK →
🇵🇱 Known in Poland as
Medicines sold in Poland with the same active substance: W Polsce znany jako
- MepseviiVestronidase alfa · injection / infusion
Same active substance. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Polish medicines in the UK →
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Ask anything about Mepsevii 2 mg/mL concentrate for solution for infusion. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.