Kovaltry

What Is Kovaltry and What Is It Used For?

Kovaltry contains octocog alfa, a recombinant human coagulation factor VIII used to treat and prevent bleeding in patients with hemophilia A. It works by temporarily replacing the missing factor VIII protein that is essential for normal blood clotting.

Kovaltry belongs to the class of antihemophilic factors. It contains octocog alfa, a full-length recombinant human coagulation factor VIII glycoprotein produced in baby hamster kidney (BHK) cells using recombinant DNA technology. Importantly, no human- or animal-derived components are added during the manufacturing process, which significantly reduces the theoretical risk of transmitting infectious agents.

Factor VIII is a naturally occurring protein in the blood that plays a critical role in the coagulation cascade. When a blood vessel is injured, factor VIII works together with factor IX (also called the “tenase complex”) to activate factor X, which ultimately leads to the formation of a stable fibrin clot. In patients with hemophilia A, factor VIII is either absent or present in insufficient quantities, which means that bleeding episodes last longer than normal and may occur spontaneously in joints, muscles, and internal organs.

By intravenously infusing Kovaltry, the missing factor VIII is temporarily replaced, restoring the blood’s ability to form clots. This replacement therapy allows patients to control active bleeding episodes and, when used prophylactically, helps prevent bleeds from occurring in the first place. The World Federation of Hemophilia (WFH) recommends regular prophylaxis as the standard of care for patients with severe hemophilia A, as it has been shown to significantly reduce the frequency of joint bleeds and prevent the development of chronic joint damage (hemophilic arthropathy).

Kovaltry is indicated for the following uses in patients of all ages with hemophilia A:

• On-demand treatment: Control of acute bleeding episodes, including joint bleeds (hemarthrosis), muscle bleeds, mucosal bleeding, and internal hemorrhage
• Routine prophylaxis: Regular preventive treatment to reduce the frequency and severity of bleeding episodes
• Perioperative management: Prevention and control of bleeding during and after surgical procedures

What Should You Know Before Taking Kovaltry?

Before starting Kovaltry, inform your doctor about any allergies (especially to mouse or hamster proteins), previous factor VIII inhibitor development, heart disease, or if you use a central venous catheter. Kovaltry should only be initiated under the supervision of a physician experienced in treating hemophilia.

Contraindications

You should not use Kovaltry if any of the following apply to you:

• Allergy to octocog alfa or any of the other ingredients in Kovaltry (listed in the contents section below)
• Allergy to mouse proteins – trace amounts of mouse-derived proteins may be present from the manufacturing process
• Allergy to hamster proteins – octocog alfa is produced in baby hamster kidney (BHK) cells, and trace amounts of hamster protein may be present

If you are unsure whether any of these apply to you, consult your doctor or pharmacist before using Kovaltry. Allergic reactions to factor VIII products can be serious and potentially life-threatening.

Warnings and Precautions

Talk to your doctor or pharmacist before using Kovaltry if you experience or have experienced any of the following:

• Allergic or anaphylactic reactions: If you develop tightness in the chest, dizziness (especially when standing), itchy hives, wheezing, nausea, or faintness during or after the injection, these may be signs of a rare but serious allergic reaction. Stop the infusion immediately and seek emergency medical attention.
• Uncontrolled bleeding despite usual dose: This may indicate the development of factor VIII inhibitors (antibodies against factor VIII). Inhibitors are a known complication of all factor VIII replacement therapies. They prevent the treatment from working properly, particularly at high concentrations. If your bleeding cannot be controlled with your usual dose of Kovaltry, contact your doctor immediately.
• Previous inhibitor development: If you have previously developed factor VIII inhibitors with another product, there is a risk that inhibitors may recur when switching to Kovaltry or any other factor VIII product.
• Confirmed heart disease or risk factors for heart disease: Factor VIII replacement therapy may increase the risk of cardiovascular events in certain patients. Your doctor will assess your individual risk.
• Central venous access device (CVAD): If you receive Kovaltry through a central venous catheter, you may be at increased risk for catheter-related complications, including local infections, bacteremia (bacteria in the bloodstream), and thrombosis (blood clot formation) at the catheter site.

Use in Children and Adolescents

Kovaltry can be used in patients of all ages, including newborns and infants. The warnings and precautions described above apply equally to children and adults. Children under 12 years of age typically have a faster clearance rate for factor VIII, which means they may require higher doses or more frequent injections to maintain adequate factor VIII levels compared to adults and adolescents. Your child’s treating hematologist will calculate the appropriate dose based on body weight, severity of hemophilia, and individual pharmacokinetic response.

Pregnancy and Breastfeeding

Hemophilia A is an X-linked recessive condition that predominantly affects males. There is very limited clinical experience with the use of factor VIII products during pregnancy and breastfeeding in female carriers. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using Kovaltry. Your doctor will decide whether the potential benefits outweigh any potential risks.

It is not known whether octocog alfa is excreted in human breast milk. Since factor VIII is a naturally occurring protein in the body, it is not expected to have adverse effects on the breastfed infant. However, a decision on whether to continue breastfeeding or continue Kovaltry therapy should be made in consultation with your doctor.

Driving and Operating Machinery

Kovaltry has no known effect on the ability to drive and use machines under normal circumstances. However, if you experience dizziness or other symptoms that affect your concentration and reaction time during or after the injection, you should not drive or operate machinery until the symptoms have resolved.

Sodium Content

Kovaltry contains less than 1 mmol (23 mg) sodium per dose, meaning it is essentially “sodium-free.” This is relevant for patients on a sodium-restricted diet.

How Does Kovaltry Interact with Other Drugs?

No specific drug interactions with Kovaltry have been identified in clinical studies. However, you should always inform your doctor about all medications you are taking, including prescription medicines, over-the-counter products, and herbal supplements.

Unlike many small-molecule drugs that are metabolised by liver enzymes, Kovaltry is a recombinant protein that functions by directly replacing the missing coagulation factor VIII. As such, it does not undergo hepatic metabolism through the cytochrome P450 enzyme system and has no known pharmacokinetic drug-drug interactions. The factor VIII protein is cleared from the circulation through natural physiological processes, including uptake by the reticuloendothelial system.

While there are no formally documented interactions, some clinical considerations are important:

Kovaltry must not be mixed with other infusion solutions or medications. Only the components provided in the Kovaltry packaging (vial adapter, prefilled syringe with solvent, and infusion set) should be used for reconstitution and administration. Do not use the infusion set provided with Kovaltry to draw blood, as it contains an in-line filter.

What Is the Correct Dosage of Kovaltry?

The dose of Kovaltry is measured in International Units (IU) and is individually calculated based on body weight, the severity of hemophilia A, the location and extent of bleeding, and whether the patient has developed inhibitors. For prophylaxis, the usual dose is 20–40 IU per kg body weight given two to three times per week.

Treatment with Kovaltry should be initiated and supervised by a physician experienced in the management of hemophilia. Always use Kovaltry exactly as your doctor has prescribed. Do not change the dose or frequency without consulting your doctor.

Treatment of Bleeding Episodes

For on-demand treatment of active bleeding, your doctor will calculate the appropriate dose based on the following factors:

• Your body weight
• The severity of your hemophilia A
• The location and severity of the bleeding episode
• Whether you have developed inhibitors and their titre
• The target factor VIII level needed for the clinical situation

As a general dosing principle, 1 IU of factor VIII per kg body weight raises the plasma factor VIII activity by approximately 2 IU/dL (2%). This pharmacokinetic relationship allows your doctor to calculate the precise dose needed to achieve a target factor VIII level.

Prophylaxis (Preventive Treatment)

Patients with Inhibitors

If you have developed factor VIII inhibitors, a higher dose of Kovaltry may be required to achieve adequate bleeding control. Your doctor will determine the dose based on your inhibitor titre (measured in Bethesda Units). In cases of low-titre inhibitors (<5 BU), higher doses of factor VIII may be sufficient. For high-titre inhibitors (≥5 BU), factor VIII replacement is generally ineffective, and your doctor may prescribe alternative treatments such as bypassing agents (activated prothrombin complex concentrate or recombinant factor VIIa) or consider immune tolerance induction (ITI) therapy.

Missed Dose

If you forget to take a prophylactic dose, administer it as soon as you remember, then continue with your regular dosing schedule as prescribed by your doctor. Do not use a double dose to make up for a missed one. If you frequently miss doses, speak with your healthcare team about strategies to improve adherence, such as setting reminders or adjusting the dosing schedule.

Overdose

How Kovaltry Is Prepared and Administered

Kovaltry is administered by intravenous injection (directly into a vein), typically over 2 to 5 minutes depending on the total volume and patient comfort. The reconstituted solution must be used within 3 hours of preparation and should not be refrigerated after reconstitution.

The reconstitution and injection process involves the following key steps:

1. Wash your hands thoroughly with soap and warm water
2. Warm the unopened vial and prefilled syringe to a comfortable temperature (do not exceed 37°C)
3. Remove the protective cap from the vial and clean the rubber stopper with an alcohol swab
4. Attach the vial adapter by pressing it firmly onto the powder vial
5. Prepare the prefilled syringe by attaching the plunger rod and removing the syringe cap
6. Connect the syringe to the vial adapter and slowly transfer the solvent into the powder vial
7. Gently swirl the vial until all powder is dissolved – do not shake
8. Inspect the solution for particles or discolouration – do not use if the solution is cloudy or contains visible particles
9. Withdraw the solution into the syringe and connect the infusion set
10. Administer the injection slowly into a vein over 2–5 minutes (maximum infusion rate: 2 mL/min)

What Are the Side Effects of Kovaltry?

The most serious side effect of Kovaltry is the development of factor VIII inhibitors, particularly in previously untreated patients. Common side effects include injection site reactions, headache, fever, stomach discomfort, and rash. Allergic reactions can occur but are rare.

Like all medicines, Kovaltry can cause side effects, although not everybody gets them. The most clinically significant adverse event is the development of inhibitors (neutralising antibodies) against factor VIII, which can render the treatment ineffective. All patients receiving Kovaltry should be monitored regularly for inhibitor development.

If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. Reporting suspected side effects to your national medicines agency helps ensure ongoing monitoring of the medicine’s benefit-risk balance.

How Should You Store Kovaltry?

Store Kovaltry in a refrigerator (2–8°C), protected from light, in its original packaging. Do not freeze. The product can alternatively be stored at room temperature (up to 25°C) for up to 12 months. Once reconstituted, the solution must be used within 3 hours.

Keep Kovaltry out of the sight and reach of children. Do not use this medicine after the expiry date (EXP) printed on the labels and cartons. The expiry date refers to the last day of the stated month.

The following storage conditions apply:

• Refrigerated storage (preferred): 2–8°C. Do not freeze. Store in the original outer carton to protect from light.
• Room temperature storage: Kovaltry may be stored at room temperature (up to 25°C) for a single period of up to 12 months, provided it remains in the outer carton. Once removed from refrigeration, note the new expiry date on the outer carton. The product expires either 12 months after first room-temperature storage or at the original expiry date on the packaging, whichever comes first.
• After reconstitution: Use the prepared solution within 3 hours. Do not refrigerate the reconstituted solution. The product is for single use only – discard any unused solution.

Do not use Kovaltry if the reconstituted solution contains particles or appears cloudy. Dispose of unused or expired medicine at your pharmacy. Do not flush down the toilet or throw away in household waste, as this helps protect the environment.

What Does Kovaltry Contain?

Each vial of Kovaltry contains octocog alfa (recombinant human coagulation factor VIII) in strengths of 250, 500, 1000, 2000, or 3000 IU as a white to slightly yellowish powder, along with a prefilled syringe of clear solvent for reconstitution.

Active Ingredient

The active substance is octocog alfa (recombinant human coagulation factor VIII). Each vial of Kovaltry contains nominally 250, 500, 1000, 2000, or 3000 IU of octocog alfa. The actual potency is stated on the label of each individual vial and is determined by chromogenic assay.

Inactive Ingredients (Excipients)

The other ingredients of the powder are:

• Sucrose (stabiliser)
• Histidine (buffer)
• Glycine (E 640, stabiliser)
• Sodium chloride
• Calcium chloride dihydrate (E 509)
• Polysorbate 80 (E 433, surfactant)
• Acetic acid, glacial (E 260, pH adjuster)

The solvent is water for injections, provided in a prefilled syringe.

Sodium Content

This medicine contains less than 1 mmol (23 mg) sodium per dose, meaning it is essentially “sodium-free.”

Product Appearance and Packaging

Powder: White to slightly yellowish, dry powder (lyophilisate).

Solvent: Clear liquid (water for injections) in a prefilled syringe.

Each individual pack of Kovaltry contains: one glass vial with powder, one prefilled syringe with solvent, a separate plunger rod, a vial adapter, and an infusion set (for intravenous administration). Kovaltry is available as single packs and multipacks of 30 single packs. Not all pack sizes may be marketed in your country.

Marketing authorisation holder and manufacturer: Bayer AG, 51368 Leverkusen, Germany.

How Does Kovaltry Work in the Body?

Kovaltry works by replacing the missing coagulation factor VIII in patients with hemophilia A. Once infused intravenously, octocog alfa functions identically to endogenous factor VIII, participating in the coagulation cascade to form stable blood clots and control bleeding.

The blood coagulation system is a complex cascade of enzymatic reactions that ultimately leads to the formation of a fibrin clot at the site of vascular injury. Factor VIII plays a central role in the intrinsic pathway of coagulation. When activated by thrombin, factor VIII becomes factor VIIIa, which serves as a cofactor for factor IXa. Together, the factor VIIIa/IXa complex (known as the “tenase complex”) activates factor X, which triggers the common pathway of coagulation leading to thrombin generation and fibrin clot formation.

In patients with hemophilia A, factor VIII is either absent (severe hemophilia, <1% factor VIII activity) or present in reduced quantities (moderate hemophilia, 1–5%; mild hemophilia, 5–40%). Without adequate factor VIII, the intrinsic coagulation pathway is impaired, leading to prolonged or uncontrolled bleeding. Bleeding can occur spontaneously (particularly into joints and muscles) or following trauma or surgery.

When Kovaltry is infused intravenously, the recombinant factor VIII protein enters the bloodstream and immediately becomes available to participate in the coagulation cascade. It binds to von Willebrand factor (VWF) in the circulation, which protects it from premature degradation and extends its half-life. When a bleeding event occurs, factor VIII is activated and dissociates from VWF to participate in the tenase complex, ultimately enabling normal clot formation at the site of injury.

Pharmacokinetic Profile

After intravenous infusion, Kovaltry achieves peak factor VIII activity immediately. One IU of factor VIII per kg body weight raises plasma factor VIII activity by approximately 2 IU/dL (2%), a relationship known as the “in vivo recovery.” This allows clinicians to predictably calculate the dose needed to achieve a target factor VIII level.

The elimination half-life of Kovaltry is approximately 12–14 hours in adults and adolescents (≥12 years) and approximately 9–11 hours in children under 12 years. The shorter half-life in children is due to a larger volume of distribution relative to body weight and faster clearance. This pharmacokinetic difference explains why children typically require higher or more frequent doses to maintain adequate factor VIII levels for prophylaxis. Steady-state trough levels are typically achieved after 3–5 days of regular prophylactic dosing.

Kovaltry has a comparable pharmacokinetic profile to other full-length recombinant factor VIII products. However, individual variation is significant, and many hemophilia treatment centres now use pharmacokinetic-guided dosing (also known as “PK-tailored prophylaxis”) to optimise the dosing regimen for each patient based on their individual factor VIII half-life and clearance.

Frequently Asked Questions About Kovaltry