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.
Replenine-VF 50 IU/ml powder and solvent for solution for injection
⚠ 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 Factor ix 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
Replenine-VF contains a high purity factor IX concentrate, a protein that is used to prevent and treat bleeding in patients with haemophilia B (an inherited shortage of factor IX in the blood). Your doctor will explain further why this medicine has been given to you. Replenine-VF can be used in patients of all age groups. 2.
What you need to know before you take it
e Replenine-VF
Do not use Replenine-VF if you are allergic (hypersensitive) to human coagulation factor IX or any of the other ingredients of this medicine (listed in section 6). Talk to your doctor if you think this applies to you. Warnings and precautions Talk to your doctor, pharmacist or nurse before using Replenine-VF if you: have heart or liver disease have a risk of blood clotting have had surgery recently have a high level of antibodies to factor IX (Your doctor may give you an alternative treatment). Your doctor or nurse will check the level of factor IX and antibodies in your blood before and after treatment, especially for your first injections. The formation of inhibitors (antibodies) is a known complication that can occur during treatment with all factor IX medicines. These inhibitors, especially at high levels, stop the treatment working properly and you or your child will be monitored carefully for the development of these inhibitors. If your or your child's bleeding is not being controlled with Replenine-VF, or if you suddenly have unusual bruising and feel very unwell, tell your doctor immediately. 2
If you require a central venous access device (CVAD) for the administration of Replenine-VF, you may be at risk of complications including local infections, bacteria in the blood (bacteraemia) and the blood clot at the catheter site. Virus safety When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include: careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded the testing of each donation and pools of plasma for signs of virus/infections the inclusion of steps in the processing of the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses or other types of infections. The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-enveloped hepatitis A and parvovirus B19 viruses. It is strongly recommended that every time you receive a dose of Replenine-VF, the name and batch number of the product are recorded to maintain a record of the batches used. Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly or repeatedly receive human plasma-derived factor IX products. Children and adolescents The listed warnings and precautions apply to both adults and children. Other medicines and Replenine-VF Tell your doctor if you are taking, or have recently taken, any other medicines. Pregnancy, breast-feeding and fertility 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. Driving and using machines Replenine-VF does not affect your ability to drive or operate machines. Replenine-VF contains sodium This medicine contains up to 83 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 4% of the recommended maximum daily dietary intake of sodium for an adult. 3.
How to take it
Replenine-VF
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure. Replenine-VF should be injected directly into a vein. Before injecting this medicine, you should have received training by your healthcare professional on how to do this.
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Use only the recommended injection equipment provided with your medicine. Your doctor will explain how much you should use and when you should use it. Your doctor will tell you your dose and how many vials you should use to inject the dose you need. If further treatment is needed, doses may be repeated. Your doctor will advise you if this is necessary. The amount of factor IX you or your child need and the duration of treatment will depend on several factors, such as your body weight, the severity and nature of your condition, the site and intensity of the bleeding or the need to prevent bleeding during an operation or medical procedure. When to inject Replenine-VF Replenine-VF can be used to stop bleeding, when it occurs, or to prevent bleeding from happening. When to inject Replenine-VF to stop bleeding: • The medicine should be injected when the first sign of bleeding occurs. • The injection should be repeated as necessary to stop the bleeding. • Each individual bleed should be judged on its own severity. • If you are using this product for the first time, your doctor will supervise you. If you are using Replenine-VF to prevent bleeding from happening, your doctor will tell you when to inject your medicine. Dissolving your medicine before use
1. 2. 3.
Vial of Replenine-VF
Quantity of water supplied
500 IU 1000 IU
10 ml 20 ml
Quantity of water required for Half Volume 5 ml 10 ml
Replenine-VF must only be dissolved in the water provided with the product. Before you remove the cap, make sure that the vials of Replenine-VF and the water supplied, are both at room temperature (between 20°C and 25°C). Your doctor will tell you if you can dissolve Replenine-VF in half the normal volume of water.
How to Dissolve Replenine-VF You can dissolve your product in two ways using the Transfer Device called Mix2VialTM: A) Dissolving in Full Volume or B) Dissolving with Half Volume A) Dissolving in Full Volume The Mix2VialTM transfer device is provided with your product for needle-free, easy and safe use. Step 1
- Remove the cap from the product vial and clean the top of the stopper with an alcohol swab.
- Repeat this step with the water vial.
- Peel back the top of the Mix2VialTM transfer device package but leave the device in the package.
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Step 2
- Place the blue end of the Mix2VialTM transfer device on the water vial and push straight down until the spike penetrates the rubber stopper and snaps into place.
- Remove the plastic outer packaging from the Mix2VialTM transfer device and discard it, taking care not to touch the exposed end of the device.
Step 3
- Turn the water vial upside down with the device still attached.
- Place the clear end of the Mix2VialTM transfer device on the product vial and push straight down until the spike penetrates the rubber stopper and snaps into place.
Step 4
- The water will be pulled into the product vial by the vacuum contained within it.
- Gently swirl the vial to make sure the product is thoroughly mixed. Do not shake the vial.
- A clear or slightly pearl-like solution should be obtained, usually in about 2 to 2 1⁄2 minutes (5 minutes maximum).
Step 5
- Separate the empty water vial and blue part from the clear part by unscrewing anti-clockwise.
- Draw air into the syringe by pulling the plunger to the required volume of water added.
- Connect the syringe to the white filter.
- Push the air in the syringe into the vial. Step 6
- Immediately invert the vial of solution which will be drawn into the syringe.
- Disconnect the filled syringe from the Mix2VialTM transfer device.
- The product is now ready for administration. Follow the normal safety practices for administration. Use the product immediately after reconstitution, the product must not be stored.
Note: If you have to use more than one vial to make up your required dose, repeat Steps 1 to 6 withdrawing the solution in the vial into the same syringe. The transfer device supplied with your product is sterile and cannot be used more than once. B) Dissolving with Half Volume To use the Mix2VialTM transfer device when dissolving Replenine-VF in half volume, it is first necessary to remove and discard half the volume of water from the vial of sterile water. See the table above, under "Dissolving your medicine before use", for the quantity of water needed. • Remove the cap from the vial of water and clean the top of the stopper with an alcohol swab.
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• • •
Pierce the stopper of the vial of water with a needle and syringe and draw up half the volume of sterile water. Check that the correct amount is withdrawn. The needle and syringe can now be safely disposed of. The remaining water in the vial will be used for dissolving (half the original volume).
To complete the dissolving process follow steps 1-6 in Section A above. The product is then ready for administration. Do not use this medicine if:
- the water is not pulled into the product vial with either method of reconstitution (this indicates a loss of vacuum in the vial, so the product must not be used).
- the dissolved product and water form a gel or a clot or if the solution is cloudy
- there are any particles in the syringe If any of these happen, tell your doctor or pharmacist, reporting the batch number printed on the vials. If you use more Replenine-VF than you should If you think you may be using too much, stop the injection and tell your doctor. If you know you have used too much, tell your doctor as soon as possible. If you forget to use Replenine-VF Do not use a double dose to make up for a forgotten dose. Inject your normal dose as soon as you remember and then continue to use as told by your doctor If you stop using Replenine-VF Always talk to your doctor before deciding to stop your treatment. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 4.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Stop the injection and tell your doctor immediately or go to the emergency department of your nearest hospital, if you get any of the following symptoms: • swelling around the face and throat • nettle-rash (urticaria) • restlessness • burning and stinging at the infusion site • hives • rapid heart beat • chills • low blood pressure • tightness of the chest or wheezing • flushing • lethargy • tingling • nausea or vomiting These symptoms may worsen into severe shock. The above allergic-type reactions are rare (may affect up to 1 in 1,000 people). Kidney problems (such as nephrotic syndrome) have been reported in some haemophilia B patients who have inhibitors (antibodies) to factor IX and a history of allergic reaction to factor IX containing products. This may cause fluid retention (swelling or weight gain) or changes in your urine. 6
The use of low purity factor IX products has been associated with heart attack, blood clots and abnormal blood coagulation. The use of high purity factor IX, such as Replenine-VF, is rarely associated with such side effects. Other possible side effects Common (may affect up to 1 in 10 people) • Reaction at the injection site, e.g. irritation, inflammation. • Headache. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor. Reporting of side effects 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 the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. 5.
How to store it
Replenine-VF
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 containers after "EXP". The expiry date refers to the last day of that month. Store in a refrigerator (2°C to 8°C). Do not freeze. Can be stored up to 3 months at 25°C. Record date of removal from refrigerator on carton. Keep the vials in the outer carton in order to protect from light. Do not use this medicine if you notice small bits in the dissolved product. Once reconstituted, Replenine-VF must be used immediately or within 1 hour. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist or doctor how to throw away medicines you no longer use. These measures will help protect the environment. 6.
Contents of the pack and other information
What Replenine-VF contains The active substance is human coagulation factor IX. The other ingredients are: lysine hydrochloride, glycine, sodium citrate, citric acid monohydrate, disodium phosphate dihydrate, sodium chloride and sodium hydroxide (for pH adjustment). What Replenine-VF looks like and contents of the pack Replenine-VF is a white or pale yellow coloured powder in quantities of 500 International Units (IU) or 1000 IU in glass vials. These vials are closed with a rubber stopper under vacuum, held with a tamper-evident cap. Replenine-VF should only be reconstituted with water for injections which is supplied with ReplenineVF in vials. Provided with the product is a Mix2VialTM transfer device to enable needle-free, easy and safe reconstitution. 7
An administration user kit for administrative components can be provided separately upon request. Marketing Authorisation Holder Bio Products Laboratory Limited Dagger Lane Elstree Herts WD6 3BX United Kingdom Tel: +44 (0) 20 8957 2255 e-mail: [email protected] Manufacturer Bio Products Laboratory Limited, Dagger Lane, Elstree, Borehamwood, WD6 3BX, United Kingdom This leaflet was last revised in February 2023.
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Frequently asked questions about Replenine-VF 50 IU/ml powder and solvent for solution for injection
How do I take Replenine-VF 50 IU/ml powder and solvent for solution for injection?
Replenine-VF 50 IU/ml powder and solvent for solution for injection comes as injection containing 50iu/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 Replenine-VF 50 IU/ml powder and solvent for solution for injection?
The active substance in Replenine-VF 50 IU/ml powder and solvent for solution for injection is factor ix.
Are there equivalent medicines to Replenine-VF 50 IU/ml powder and solvent for solution for injection?
Medicines with the same active substance, strength and form include: Replenine-VF 50 IU/ml powder and solvent for solution for injection (Filter Needle). They are interchangeable only if your prescriber or pharmacist says so.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Replenine-VF 50 IU/ml powder and solvent for solution for injection, 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 Replenine-VF 50 IU/ml powder and solvent for solution for injection 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: factor ix
- 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
Treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency).
Replenine-VF can be used for all age groups.
4.2. Posology and method of administration
Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.
Treatment monitoring
During the course of treatment, appropriate determination of factor IX levels is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor IX, demonstrating different half‑lives and recoveries. Dose based on bodyweight may require adjustment and monitoring of factor IX levels in underweight or overweight patients.
In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor IX activity) is indispensable.
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor IX activity in patients' blood samples, plasma factor IX activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. This is of importance particularly when changing the laboratory and/or reagents used in the assay.
Posology
Dose and duration of the substitution therapy depend on the severity of the factor IX deficiency, on the location and extent of the bleeding and on the patient's clinical condition.
The number of units of factor IX administered is expressed in International Units (IU), which are related to the current WHO standard for factor IX products. Factor IX activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to an International Standard for factor IX in plasma).
One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX in one ml of normal human plasma.
On demand treatment
The calculation of the required dose of factor IX is based on the empirical finding that 1 International Unit (IU) of factor IX per kg body weight raises the plasma factor IX activity by 1.16% of normal activity. The required dose is determined using the following formula:
Required units = body weight (kg) x desired factor IX rise (%) or (IU/dl) x 0.85
The amount to be administered and the frequency of administration should always be orientated to the clinical effectiveness in the individual case.
In the case of the following haemorrhagic events, the factor IX activity should not fall below the given plasma activity level (in IU/dl) in the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:
Degree of haemorrhage/
Type of surgical procedure
Factor IX level required (%) or (IU/dl)
Frequency of doses (hours)/
Duration of therapy (days)
Haemorrhage
Early haemarthrosis, muscle bleeding or oral bleeding
20-40
Repeat every 24 hours. At least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved.
More extensive haemarthrosis, muscle bleeding or haematoma
30-60
Repeat infusion every 24 hours for 3 to 4 days or more until pain and acute disability are resolved.
Life threatening haemorrhages
60-100
Repeat infusion every 8 to 24 hours until threat is resolved.
Surgery
Minor surgery including tooth extraction
30-60
Every 24 hours, at least 1 day, until healing is achieved.
Major surgery
80-100
(pre- and post-operative)
Repeat infusion every 8 to 24 hours until adequate wound healing, then therapy for at least another 7 days to maintain a factor IX activity of 30% to 60% (IU/dl).
Prophylaxis
For long term prophylaxis against bleeding in patients with severe haemophilia B, the usual doses are 20 to 40 IU of factor IX per kilogram of body weight at intervals of 3 to 4 days.
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.
Continuous infusion
Prior to surgery, a pharmacokinetic analysis should be performed to obtain an estimate of clearance.
The initial infusion rate can be calculated as follows:
Clearance x desired steady state level = infusion rate (IU/kg/hr).
After the initial 24 hours of continuous infusion, the clearance should be calculated again every day using the steady state equation with the measured level and the known rate of infusion (see section 5.2).
Paediatric population
Children under 12 years of age
There are limited data on the use of Replenine-VF in children under 12 years of age (see section 5.1).
The recommended dose and dosing frequency in adolescents (aged 12-17 years) are as recommended for adults.
Method of administration
Intravenous use.
Replenine-VF should be administered via the intravenous route at a rate not exceeding 3 ml per minute.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4. Special warnings and precautions for use
Traceability
In order to improve traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity
Allergic type hypersensitivity reactions are possible with Replenine-VF. The product contains traces of human proteins other than factor IX. If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the medicinal product immediately and contact their physician. Patients/Caregivers should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis.
In case of shock, standard medical treatment for shock should be implemented.
Inhibitors
After repeated treatment with human coagulation factor IX products, patients should be monitored for the development of neutralising antibodies (inhibitors) that should be quantified in Bethesda Units (BU) using appropriate biological testing.
There have been reports in the literature showing a correlation between the occurrence of a factor IX inhibitor and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated for the presence of an inhibitor. It should be noted that patients with factor IX inhibitors may be at an increased risk of anaphylaxis with subsequent challenge with factor IX.
Because of the risk of allergic reactions with factor IX products, the initial administrations of factor IX should, according to the treating physician's judgement, be performed under medical observation where proper medical care for allergic reactions could be provided.
Thromboembolism
Because of the potential risk of thrombotic complications, clinical surveillance for early signs of thrombotic and consumptive coagulopathy should be initiated with appropriate biological testing when administering this medicinal product to patients with pre-existing risk factors, e.g. liver disease, to patients post-operatively, to new-born infants, or to patients at risk of thrombotic phenomena or DIC. In each of these situations, the benefit of treatment with Replenine-VF should be weighed against the risk of these complications.
Cardiovascular events
In patients with existing cardiovascular risk factors, substitution therapy with factor IX may further increase the cardiovascular risk.
Catheter-related complications
If a central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteraemia and catheter site thrombosis should be considered.
Transmissible agents
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV), and for the non-enveloped hepatitis A and parvovirus B19 viruses.
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived factor IX products.
Paediatric population
The listed warnings and precautions apply both to adults and children.
4.5. Interaction with other medicinal products and other forms of interaction
No interactions of human coagulation factor IX products with other medicinal products have been reported.
4.6. Fertility, pregnancy and lactation
Animal reproduction studies have not been conducted with factor IX. Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy and breast-feeding is not available. Therefore, factor IX should be used during pregnancy and lactation only if clearly indicated.
4.7. Effects on ability to drive and use machines
Replenine-VF has no influence on the ability to drive and use machines.
4.8. Undesirable effects
Summary of the safety profile
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed rarely. In some cases, these reactions have progressed to severe anaphylaxis (including shock), and they have occurred in close temporal association with development of factor IX inhibitors (see also section 4.4). Nephrotic syndrome has been reported following attempted immune tolerance induction in haemophilia B patients with factor IX inhibitors and a history of allergic reaction.
Patients with haemophilia B may develop neutralising antibodies (inhibitors) to factor IX. If such inhibitors occur, the condition will manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia centre be contacted.
There is a potential risk of thromboembolic episodes following the administration of factor IX products, with a higher risk for low purity preparations. The use of low purity factor IX products has been associated with instances of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism. The use of high purity factor IX is rarely associated with such adverse reactions.
For safety information with respect to transmissible agents, see section 4.4.
Tabulated list of adverse reactions
The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level).
Frequencies have been evaluated according to the following convention: 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); very rare (<1/10,000), not known (cannot be estimated from the available data). The table lists adverse reactions reported in the clinical studies and identified in post marketing use.
MedDRA Standard System Organ Class (SOC)
Adverse reactions
Frequency
Nervous system disorders
Headache
Common
General disorders and injection site changes
Injection site reaction
Common
Paediatric population
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
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 the 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
No case of overdose with human factor IX has been reported.
💬 Ask about this leaflet
Ask anything about Replenine-VF 50 IU/ml powder and solvent for solution for injection. 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.