ReFacto AF (Moroctocog Alfa)
Recombinant Coagulation Factor VIII for Hemophilia A
ReFacto AF is a recombinant coagulation factor VIII (moroctocog alfa) used to treat and prevent bleeding episodes in patients with hemophilia A. It replaces the missing or deficient clotting factor that is essential for normal blood coagulation. ReFacto AF is approved for use in adults and children of all ages, including neonates, and can be used both for on-demand treatment of acute bleeds and for routine prophylaxis to reduce bleeding frequency.
Quick Facts
Key Takeaways
- ReFacto AF contains moroctocog alfa, a recombinant factor VIII that replaces the missing clotting factor in hemophilia A patients.
- It is administered intravenously and can be used for both on-demand treatment and prophylaxis in patients of all ages, including neonates.
- Inhibitor (antibody) development is a known complication, particularly common in previously untreated patients (more than 1 in 10).
- The product should be stored refrigerated (2–8°C) but may be kept at room temperature (up to 25°C) for up to 3 months. Once reconstituted, use within 3 hours.
- Patients allergic to hamster proteins must not use ReFacto AF, as the active substance is produced in Chinese hamster ovary (CHO) cells.
What Is ReFacto AF and What Is It Used For?
Hemophilia A is an inherited bleeding disorder caused by mutations in the gene that encodes coagulation factor VIII. This protein is a critical cofactor in the intrinsic pathway of blood coagulation, where it works alongside factor IXa to activate factor X. Without adequate factor VIII, patients experience prolonged or spontaneous bleeding episodes that can affect joints, muscles, and internal organs. The severity of hemophilia A correlates with the residual level of factor VIII activity in the blood, with severe forms defined as less than 1% of normal factor VIII levels.
ReFacto AF contains moroctocog alfa, a B-domain deleted recombinant form of human coagulation factor VIII. The protein is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. The B-domain deletion does not impair the coagulant activity of factor VIII, as this domain is naturally cleaved during activation in the coagulation cascade. By removing the B-domain, the molecule is more compact and can be produced more efficiently.
The “AF” in ReFacto AF stands for “albumin-free,” meaning that the manufacturing and formulation process does not use human or animal albumin. This reduces the theoretical risk of transmission of infectious agents through human- or animal-derived proteins. The product is purified through a series of chromatographic steps and undergoes viral inactivation and removal procedures to enhance safety.
ReFacto AF is indicated for the treatment and prophylaxis of bleeding in patients with hemophilia A (congenital factor VIII deficiency). It is approved for use in adults and children of all ages, including neonates. Prophylactic use involves regular infusions to maintain factor VIII levels high enough to prevent spontaneous bleeding, which has been shown in clinical trials to significantly reduce the frequency of bleeding episodes and protect joints from damage caused by recurrent hemarthroses.
The World Federation of Hemophilia (WFH) guidelines recommend factor VIII replacement therapy as the standard of care for hemophilia A. Both on-demand treatment (given at the time of a bleed) and prophylactic regimens are well established, with prophylaxis being the preferred approach in severe hemophilia A to prevent joint destruction and improve quality of life.
What Should You Know Before Taking ReFacto AF?
Contraindications
ReFacto AF is contraindicated in patients with known hypersensitivity to moroctocog alfa or to any of the excipients in the product formulation. Because moroctocog alfa is produced in Chinese hamster ovary (CHO) cells, patients with a confirmed allergy to hamster proteins must not use this medication. If you are unsure whether you have such an allergy, consult your healthcare provider before starting treatment.
Warnings and Precautions
Allergic and anaphylactic reactions: As with all intravenous protein products, allergic-type hypersensitivity reactions are possible with ReFacto AF. Early signs of allergic reactions include difficulty breathing, shortness of breath, swelling, hives, itching, chest tightness, wheezing, and low blood pressure. Anaphylaxis is a severe, potentially life-threatening reaction that may cause difficulty swallowing and/or breathing, facial and/or hand swelling. If any of these symptoms occur, the infusion must be stopped immediately and appropriate medical treatment must be sought. In cases of severe allergic reactions, alternative therapy should be considered.
Development of inhibitors (neutralizing antibodies to factor VIII) is a known complication that can occur during treatment with any factor VIII product. Inhibitors prevent the treatment from working as expected, leading to inadequate control of bleeding. Patients should be carefully monitored for the development of inhibitors through appropriate clinical observations and laboratory tests. If a bleed cannot be controlled with ReFacto AF, contact your healthcare provider immediately.
Inhibitor development: Among previously untreated patients (PUPs), the incidence of inhibitor development is very common (more than 1 in 10 patients). In previously treated patients (PTPs) who have had more than 150 exposure days with factor VIII products, the risk is significantly lower (less than 1 in 100). Regular monitoring of factor VIII activity levels and inhibitor titers is recommended by the WFH and the International Society on Thrombosis and Haemostasis (ISTH).
Uncontrolled bleeding: If your bleeding does not stop as expected after using ReFacto AF, seek medical attention immediately. This could indicate inhibitor development or another underlying issue that requires prompt evaluation.
Drug Interactions
No formal drug interaction studies have been conducted with ReFacto AF. No known significant interactions with other medications have been reported. However, as with any medication, you should always inform your healthcare provider and pharmacist about all prescription medications, over-the-counter drugs, and supplements you are currently taking or plan to take.
Pregnancy and Breastfeeding
Hemophilia A is an X-linked condition that almost exclusively affects males. There is limited experience with the use of factor VIII products during pregnancy and breastfeeding. If you are pregnant, planning to become pregnant, or breastfeeding, consult your healthcare provider before using ReFacto AF. Your physician will assess the potential benefits and risks on an individual basis.
Driving and Operating Machinery
ReFacto AF has no known effect on the ability to drive vehicles or operate machinery.
After reconstitution, ReFacto AF contains 1.27 mmol (29 mg) of sodium per vial, which is equivalent to approximately 1.5% of the WHO-recommended maximum daily sodium intake for adults. Depending on your body weight and dosage, you may require multiple vials per infusion. This should be considered if you are on a sodium-restricted diet.
How Does ReFacto AF Interact with Other Drugs?
Unlike many small-molecule drugs, recombinant factor VIII products such as ReFacto AF do not undergo hepatic metabolism through cytochrome P450 enzymes, which is the most common pathway for drug-drug interactions. Instead, factor VIII is a protein that is cleared from the circulation through natural physiological processes, primarily through receptor-mediated endocytosis by cells of the reticuloendothelial system.
Although no formal interaction studies have been conducted, clinicians should be aware of potential pharmacodynamic considerations when co-administering ReFacto AF with other agents that affect hemostasis. The table below summarizes medications that may warrant attention in patients receiving factor VIII replacement therapy.
| Drug / Drug Class | Type | Clinical Consideration |
|---|---|---|
| Anticoagulants (e.g., warfarin, heparin) | Pharmacodynamic | May counteract the hemostatic effect of factor VIII. Coordinate closely with your hematologist if both therapies are necessary. |
| Antiplatelet agents (e.g., aspirin, clopidogrel) | Pharmacodynamic | May increase bleeding tendency. Use with caution and medical oversight in hemophilia patients. |
| NSAIDs (e.g., ibuprofen, naproxen) | Pharmacodynamic | Can impair platelet function and increase gastrointestinal bleeding risk. Acetaminophen/paracetamol is generally preferred for pain management. |
| Emicizumab (Hemlibra) | Pharmacodynamic | Emicizumab mimics factor VIII function. Use of factor VIII products alongside emicizumab requires careful hematological supervision to avoid thrombotic complications. |
| Antifibrinolytics (e.g., tranexamic acid) | Pharmacodynamic | Often used as adjunctive therapy in hemophilia. Generally safe in combination with factor VIII but should be used under medical guidance. |
It is important to emphasize that ReFacto AF should not be mixed with other infusion solutions or medications. The product should only be reconstituted with the provided sodium chloride 0.9% solvent and administered separately through its own intravenous line.
What Is the Correct Dosage of ReFacto AF?
Factor VIII dosing in hemophilia A follows established pharmacokinetic principles. The number of international units (IU) required depends on the desired increase in factor VIII plasma level. As a general rule, 1 IU of factor VIII per kilogram of body weight raises the plasma factor VIII activity by approximately 2 IU/dL (2%). The required dose is calculated using the formula:
Required dose (IU) = Body weight (kg) × Desired factor VIII rise (IU/dL or % of normal) × 0.5
The target factor VIII level and the frequency of dosing depend on the clinical situation. The following table provides general guidance based on international recommendations from the WFH and ISTH.
| Bleed Type / Situation | Target Factor VIII Level | Duration of Treatment |
|---|---|---|
| Minor bleeding (early joint bleed, mild muscle bleed, oral bleed) | 20–40 IU/dL (20–40%) | 1–3 days; repeat every 12–24 hours until resolved |
| Moderate bleeding (muscle bleed, significant joint bleed, known trauma) | 30–60 IU/dL (30–60%) | 3–5 days or until adequate healing |
| Major/life-threatening bleeding (intracranial, GI, neck/throat, major trauma) | 60–100 IU/dL (60–100%) | 7–14 days or until adequate healing |
| Minor surgery | 30–80 IU/dL (30–80%) | 1–5 days post-operatively |
| Major surgery | 80–100 IU/dL (pre- and post-operatively) | 7–14 days post-operatively; maintain >30% for healing |
Prophylaxis
For long-term prophylaxis against bleeding in patients with severe hemophilia A, the typical regimen involves infusions of 20–40 IU per kg body weight every 2–3 days. In some patients, especially young children, more frequent dosing or dose adjustments may be necessary based on individual pharmacokinetic profiles and bleeding patterns. Prophylactic treatment has been shown in multiple randomized controlled trials to dramatically reduce annual bleeding rates, prevent joint damage, and improve quality of life compared with on-demand treatment alone.
Children
ReFacto AF can be used in children of all ages, including neonates. The dosing principles are the same as for adults, based on body weight and desired factor VIII rise. However, children, particularly younger children, may have faster factor VIII clearance rates and therefore may require more frequent dosing or higher doses per kilogram to maintain adequate trough levels. Individualized pharmacokinetic assessment is recommended to optimize prophylactic regimens in pediatric patients.
Elderly
There are no specific dose adjustments recommended for elderly patients. Clinical experience with factor VIII products in patients over 65 years is limited. As with all patients, dosing should be individualized based on clinical response, factor VIII recovery, and half-life measurements.
Overdose
No cases of overdose with ReFacto AF have been reported. If you believe you have used too much ReFacto AF, contact your healthcare provider or pharmacist immediately for guidance.
Reconstitution and Administration
ReFacto AF is supplied as a lyophilized (freeze-dried) powder that must be reconstituted with the provided pre-filled syringe containing 4 mL of sodium chloride 0.9% solution. The reconstitution should be performed using aseptic technique. Allow both the vial and solvent syringe to reach room temperature before reconstitution. Gently swirl the vial — do not shake — until the powder is completely dissolved. The resulting solution should be clear to slightly opalescent and colorless. Do not use if it appears cloudy or contains visible particles.
The reconstituted solution is administered by intravenous infusion over several minutes using the provided infusion set. Your healthcare provider will determine the appropriate infusion rate for comfort. Patients and caregivers can learn to perform self-infusion at home after receiving proper training. When traveling, bring sufficient supplies for your anticipated treatment needs and document the batch number each time you infuse.
The reconstituted solution must be used within 3 hours and should not be refrigerated after reconstitution. If you need to use more than one vial per infusion, each vial should be reconstituted separately, and the contents can be drawn up into a single syringe for administration.
What Are the Side Effects of ReFacto AF?
Like all medicines, ReFacto AF can cause side effects, although not everyone will experience them. The side effects reported in clinical trials and post-marketing surveillance are categorized below by frequency according to the Medical Dictionary for Regulatory Activities (MedDRA) convention.
If you experience any signs of a serious allergic reaction during infusion — including rash, hives, generalized itching, swelling of lips and tongue, difficulty breathing, wheezing, chest tightness, general malaise, dizziness, or loss of consciousness — stop the infusion immediately and seek emergency medical care. Severe anaphylactic reactions are uncommon (up to 1 in 100 users) but require immediate treatment.
Very Common
- Inhibitor development in previously untreated patients (PUPs)
- Headache
- Cough
- Joint pain (arthralgia)
- Fever (pyrexia)
Common
- Bleeding
- Dizziness
- Decreased appetite
- Diarrhea, vomiting, abdominal pain, nausea
- Hives (urticaria), rash, itching (pruritus)
- Muscle pain (myalgia)
- Chills
- Catheter site reaction
- Increased factor VIII antibodies on blood tests
Uncommon
- Inhibitor development in previously treated patients (PTPs)
- Severe allergic (anaphylactic) reaction
- Numbness, drowsiness, altered taste
- Chest pain, rapid heart rate, palpitations
- Low blood pressure (hypotension)
- Venous pain and redness associated with a blood clot
- Hot flushes
- Shortness of breath (dyspnea)
- Excessive sweating (hyperhidrosis)
- Weakness (asthenia)
- Injection site reactions including pain
- Mild increase in cardiac enzymes
- Elevated liver enzymes and increased bilirubin
Rare / Post-Marketing
- Thromboembolic events (in patients with risk factors)
- Nephrotic syndrome (in patients with existing inhibitors undergoing immune tolerance induction)
Understanding Inhibitor Development
Inhibitor development is one of the most clinically significant complications of factor VIII replacement therapy. Inhibitors are immunoglobulin G (IgG) antibodies, primarily of the IgG4 subclass, that neutralize the procoagulant activity of infused factor VIII. When inhibitors are present, the therapeutic response to factor VIII is diminished or absent, leading to difficulty controlling bleeds.
The risk of inhibitor development is highest during the first 50 exposure days and is influenced by several factors, including the severity of the underlying hemophilia A mutation, family history, ethnicity, treatment intensity, and immune system characteristics. Previously untreated patients with severe hemophilia A (null mutations such as large deletions or inversions of the factor VIII gene) have the highest risk, with inhibitor incidence rates reported between 25–40% across clinical studies.
If inhibitors develop, treatment strategies include immune tolerance induction (ITI), which involves regular high-dose factor VIII infusions over months to years to desensitize the immune system, or the use of bypassing agents such as activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa) for acute bleed management. The bispecific antibody emicizumab is also available for prophylaxis in patients with inhibitors.
How Should You Store ReFacto AF?
Proper storage of ReFacto AF is essential to maintain its potency and safety. The unreconstituted product should be stored and transported at refrigerated temperatures between 2°C and 8°C (36°F to 46°F). Do not freeze the product, as freezing can damage the pre-filled solvent syringe and potentially affect the integrity of the medication.
If needed, the product may be removed from the refrigerator and stored at room temperature (not exceeding 25°C / 77°F) for a single continuous period of up to three months. Record the date you remove the product from the refrigerator on the outer carton. At the end of this room-temperature storage period, the product must not be returned to the refrigerator — it must be used or discarded. This room-temperature option is particularly useful for travel or when refrigerator access is limited.
Always keep the vial in the outer carton to protect it from light. Check the expiration date on the outer carton and vial label before use. The expiration date refers to the last day of the stated month. Do not use the product after this date.
After reconstitution with the provided solvent, the solution should be used within three hours. Store the reconstituted solution at room temperature prior to administration. Do not refrigerate the reconstituted solution. Inspect the solution visually before use: it should be clear to slightly opalescent and colorless. Do not use the solution if it appears cloudy or contains visible particles.
Dispose of any unused solution, empty vials, used needles, and syringes in an appropriate sharps container or medical waste container. Do not dispose of these items in household waste or drains, as they may pose a risk to others.
What Does ReFacto AF Contain?
Active Substance
Each vial of ReFacto AF contains a nominal amount of moroctocog alfa: 250, 500, 1000, or 2000 IU. Moroctocog alfa is a recombinant human coagulation factor VIII, produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. It is a B-domain deleted form of factor VIII that retains full coagulant activity. After reconstitution with 4 mL of the provided solvent, the resulting concentrations are 62.5, 125, 250, or 500 IU per mL, respectively.
Excipients (Inactive Ingredients)
- Sucrose – acts as a stabilizer for the lyophilized formulation
- Calcium chloride dihydrate – provides calcium ions necessary for factor VIII stability
- L-Histidine – a buffer that maintains the pH of the solution
- Polysorbate 80 – a surfactant that prevents protein aggregation
- Sodium chloride – contributes to the tonicity of the reconstituted solution
Solvent
The solvent provided in the pre-filled syringe is 4 mL of sterile sodium chloride 0.9% (9 mg/mL) solution for injection.
Package Contents
Each ReFacto AF package contains:
- One vial of moroctocog alfa powder (250, 500, 1000, or 2000 IU)
- One pre-filled syringe with 4 mL sterile sodium chloride 0.9% solvent and a plunger rod
- One sterile vial adapter device for reconstitution
- One sterile infusion set
- Two alcohol swabs
- One adhesive bandage
- One gauze pad
ReFacto AF is manufactured by Wyeth Farma S.A. in Madrid, Spain, and the marketing authorization holder is Pfizer Europe MA EEIG, Brussels, Belgium. The product is approved by the European Medicines Agency (EMA) and is available in many countries worldwide.
Frequently Asked Questions About ReFacto AF
ReFacto AF is used to treat and prevent bleeding episodes in patients with hemophilia A (congenital factor VIII deficiency). It contains moroctocog alfa, a recombinant form of human coagulation factor VIII that replaces the missing clotting factor. It is approved for all age groups, including neonates, and can be used for both on-demand treatment of acute bleeds and routine prophylaxis to reduce the frequency of bleeding episodes.
ReFacto AF is given as an intravenous injection (infusion into a vein) over several minutes. The lyophilized powder must first be reconstituted with the provided 0.9% sodium chloride solvent using the vial adapter. After proper training from a healthcare provider, patients or caregivers can perform home infusions. Always use aseptic technique and inspect the reconstituted solution before administration.
Inhibitors are antibodies that your immune system may produce against the infused factor VIII. They can neutralize the medication, making it less effective or completely ineffective at controlling bleeding. Inhibitor development is most common in previously untreated patients (affecting more than 1 in 10). Your healthcare provider will monitor for inhibitors through regular blood tests. If inhibitors develop, alternative treatment strategies such as immune tolerance induction or bypassing agents may be recommended.
Yes, ReFacto AF is suitable for travel. The product can be stored at room temperature (up to 25°C) for a single continuous period of up to 3 months. Note the date you remove it from the refrigerator on the carton. Bring enough product for your expected treatment needs. Carry a letter from your healthcare provider explaining your condition and the need for injectable medication, especially when traveling by air. Consult your hemophilia treatment center before traveling for personalized advice.
Store the unreconstituted product in a refrigerator at 2–8°C. Do not freeze. Keep the vial in the outer carton to protect from light. If needed, you can store it at room temperature (up to 25°C) for up to 3 months, but do not return it to the refrigerator after that. After reconstitution, use within 3 hours and do not refrigerate the reconstituted solution. Check the expiration date before each use.
ReFacto AF is produced using Chinese hamster ovary (CHO) cells through recombinant DNA technology. Although the manufacturing process includes extensive purification steps, trace amounts of hamster-derived proteins may remain in the final product. Patients with a known allergy to hamster proteins could experience allergic reactions, including potentially severe anaphylaxis. If you are unsure about a hamster protein allergy, discuss this with your healthcare provider before starting treatment.
References
- European Medicines Agency (EMA). ReFacto AF – Summary of Product Characteristics. European Medicines Agency. Available at: ema.europa.eu/en/medicines/human/EPAR/refacto-af. Accessed January 2026.
- Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1–158. doi:10.1111/hae.14046
- World Federation of Hemophilia (WFH). Guidelines for the Management of Hemophilia. 3rd ed. Montreal: WFH; 2020. Available at: wfh.org/publications
- Peyvandi F, Mannucci PM, Garagiola I, et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. New England Journal of Medicine. 2016;374(21):2054–2064. doi:10.1056/NEJMoa1516437
- Iorio A, Stonebraker JS, Chambost H, et al. Establishing the prevalence and prevalence at birth of hemophilia in males: a meta-analytic approach using national registries. Annals of Internal Medicine. 2019;171(8):540–546. doi:10.7326/M19-1208
- Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2014;12(11):1935–1939. doi:10.1111/jth.12672
- U.S. Food and Drug Administration (FDA). ReFacto AF Prescribing Information. Available at: fda.gov. Accessed January 2026.
- British National Formulary (BNF). Moroctocog alfa. Available at: bnf.nice.org.uk. Accessed January 2026.
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, which includes specialists in hematology, clinical pharmacology, and evidence-based medicine. All medical content follows the GRADE framework for evidence quality assessment and adheres to guidelines from the World Federation of Hemophilia (WFH), European Medicines Agency (EMA), and the International Society on Thrombosis and Haemostasis (ISTH).
iMedic Medical Writers with expertise in hematology and pharmaceutical sciences. All claims are supported by peer-reviewed references and regulatory documents.
Independently reviewed by the iMedic Medical Review Board. Verified for clinical accuracy, completeness, and adherence to current international treatment guidelines.
Conflict of Interest Statement: iMedic has no financial relationship with Pfizer or any pharmaceutical manufacturer. All content is editorially independent and is not influenced by commercial interests.
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