Emicizumab- Uses, Dosage, Indications, and Adverse Reactions

Overview:

Emicizumab is a drug used for the treatment of hemophilia A by providing routine prophylaxis in order to prevent or reduce the frequency of episodes of bleeding in both adults and kids. Emicizumab received its approval from the Food and Drug Administration (FDA) in the year 2017. The drug is manufactured by Genentech, Inc.

Emicizumab is a bispecific directed antibody that is indicated for routine prophylaxis in order to prevent and reduce the frequency of bleeding episodes in both adult as well as pediatric patients, ranging from the ages of newborn to older age groups who are suffering from hemophilia A. Hemophilia A is a congenital deficiency of factor VIII with or without the inhibitors of factor VIII. The recommended loading dosage of Emicizumab is 3 mg/kg through a subcutaneous injection provided once a week for the initial four weeks, which is to be followed by a maintenance dose.

There have been cases of thrombotic microangiopathy along with thrombotic events reported while a certain cumulative amount of activated prothrombin complex concentrate or aPCC was administered for 24 hours in patients who have been receiving prophylaxis with Emicizumab. Thus, it is advised to monitor the development of any kind of thrombotic microangiopathy or thrombotic events after the administration of an activated prothrombin complex concentrate. The most common adverse effects in patients after treatment with Emicizumab with over 10 % of incidence rate include- reactions are the site of injection, headache, and episodes of arthralgia.

For Doctors:

Emicizumab is a bispecific directed antibody that is indicated for routine prophylaxis in order to prevent and reduce the frequency of bleeding episodes in both adult as well as pediatric patients, ranging from the ages of newborn to older age groups who are suffering from hemophilia A. Emicizumab is a humanized monoclonal modified immunoglobulin G4. It can also be understood to be an IgG4 bispecific antibody with binding factor IXa and binding factor X. Emicizumab has a molecular weight of approximately 145.6 kDa.

Emicizumab has been produced in genetically engineered mammalian Chinese hamster ovary cells. Emicizumab has no known structural relationship and sequence homology to factor VIII. Emicizumab does not induce nor does it enhance the development of direct inhibitors to factor VIII. Emicizumab injection is a sterile and preservative-free syringe. It is a colorless to light yellow solution and is meant for subcutaneous injection.

Emicizumab is supplied in single-dose vials. The vials contain Emicizumab at various strengths, such as 30 mg/mL, 60 mg/0.4 mL, 105 mg/0.7 mL, and 150 mg/mL. A single dose of 30 mg vial includes a 1 mL solution of Emicizumab which is equal to 30 mg, L-arginine 26.1 mg, L-histidine 3.1 mg, and poloxamer 188 0.5 mg. All of this has been adjusted to a pH of 6.0, along with L-aspartic acid.

Indications:

Emicizumab is indicated for routine prophylaxis in order to prevent and reduce the frequency of episodes of bleeding in both adults as well as pediatric patients. The age group can range from newborns to senile groups. Patients who are suffering from hemophilia A or the congenital deficiency of factor VIII may present with or without factor VIII inhibitors.

Dosage:

Emicizumab is currently available as a colorless or slightly yellow solution in a single-dose vials injection or several strengths, which are- 30 mg/mL, 60 mg/0.4 mL, 105 mg/0.7 mL, and 150 mg/mL. The recommended dosage of Emicizumab is for subcutaneous use strictly and is 3 mg/kg, which is to be administered once a week for the initial four weeks. This is to be then followed by a maintenance dose which is- 1.5 mg/kg once per week, 3 mg/kg per two weeks, or 6 mg/kg per four weeks. The selection of a maintenance dose should be completely based on the preference of the healthcare professional by taking into consideration all the regimens that can potentially increase patient adherence. It should be noted that two doses of Emicizumab on the same day must not be administered, even if it is to make up for a missed dose. All the preparation and administration instructions are to be well explained by the healthcare professional and team.

Contraindications:

There are no established contraindications of Emicizumab.

Warning:

The trials and studies that were done on Emicizumab have led to the results that there are two precautionary measures that must be noticed and kept an eye for post-prophylaxis and treatment in patients suffering from hemophilia A with Emicizumab. Mentioned below are the warnings.

• Patients who underwent Emicizumab prophylaxis were associated with the development of thromboembolism.

• Patients who underwent Emicizumab prophylaxis were associated with the development of thrombotic microangiopathy.

Adverse Reactions:

The majority of the patients who have undergone treatment with Emicizumab have reported the following adverse effects:

• Headache.

• Nausea.

• Thrombotic microangiopathy.

• Thromboembolism.

• Arthralgia.

• Pain at the site of injection.

• Skin necrosis.

• Superficial thrombophlebitis.

Clinical Studies:

Since clinical trials are generally conducted under widely varying conditions, the rates of adverse reactions that are observed within the clinical trials of Emicizumab cannot be compared to rates in the clinical trials of any other drug and thus may not reflect the rates observed in clinical practice. The clinical trials done for Emicizumab was a randomized trial in adults as well as adolescent patients. The single-arm trial was additionally conducted in pediatric patients. There was a dose-finding trial done as well that included 391 patients suffering from hemophilia A, all of whom were male. The median duration of exposure to Emicizumab during the course of the study was 34.1 weeks. The most common adverse effects established post the study were headache, arthralgia, and pain at the injection site.

Drug Interactions:

Clinical studies have shown that the concomitant use of Emicizumab with an activated prothrombin complex concentrate or aPCC results in hypercoagulability.

Use in Specific Population:

Pregnancy: There are no available data on Emicizumab and its use in pregnant females to establish any kind of drug-associated risk of major birth defects and miscarriage. It is additionally not known if Emicizumab may lead to any sort of fetal harm after being administered to a pregnant female or if it has the potential to affect the reproduction capacity of the female. Emicizumab is to be prescribed during pregnancy strictly if the potential benefit of the drug for the mother outweighs the risk to the fetus.

Lactation: There are no established results regarding the presence of the components of Emicizumab in human milk, the effects of the drug on the breastfed child, and the effects on milk production in the mother. Human IgG is always present in human milk. The developmental as well as the health benefits of breastfeeding, should be taken into consideration along with the breast-feeding female’s clinical need for Emicizumab along with any potential adverse effects on the child from Emicizumab or from any kind of underlying maternal condition.

Pediatric Use: The safety and efficacy of Emicizumab have been established in pediatric patients as well as adolescents in several clinical studies.

Geriatric Use: Due to an insufficient number of patients who were above the age of 65 years, there has not been an established safety and effectiveness of Emicizumab in patients suffering from hemophilia A in the geriatric age group.

Clinical Pharmacology:

Mechanism of Action: Emicizumab bridges the activated factor IX and factor X in order to restore the standard function of missing an activated factor VIII that is required for normalized and effective hemostasis.

Absorption: The absolute bioavailability after a subcutaneous administration of 1 mg/kg is anywhere between 80.4 % and 93.1 %.

Distribution: The mean apparent volume of distribution of Emicizumab is 10.4 L, which equals 26 %.

Elimination: The mean elimination half-life of Emicizumab is anywhere between 27 days to 37 days.

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Studies to understand carcinogenesis, mutagenesis, and fertility changes have not been conducted in order to conclude any particular evidence on the same for Emicizumab.

Storage: Emicizumab must be stored in the refrigerator at a temperature between 2 degrees Celcius to 8 degrees Celsius, which equals 36 degrees Fahrenheit to 46 degrees Fahrenheit. It must not be frozen, nor should it be shaken before use. Emicizumab must be protected from sunlight at all costs.

For Patients:

What Is Hemophilia A?

Hemophilia A is referred to as the genetic deficiency in clotting factor VIII. This deficiency leads to an increased frequency of bleeding. The disease is mostly seen in males. In most cases, hemophilia A is inherited. This inheritance is present as an X-linked recessive trait. The most common clinical manifestation of this disease is uncontrolled or prolonged bleeding from cuts and wounds.

What Is the Most Important Information to Know About Emicizumab?

Emicizumab is known to increase the potential of the blood to begin clotting. All the guidelines to be followed have been provided by the healthcare provider and team. The drug must be monitored with tests such as D Dimers amd APTT.

What Are the Side Effects of Emicizumab?

The majority of the patients who have undergone treatment with Emicizumab have reported the following side effects:

• Headache.

• Nausea.

• Thrombotic microangiopathy.

• Thromboembolism.

• Arthralgia.

• Pain at the site of injection.

• Skin necrosis.

• Superficial thrombophlebitis.

• Confusion.

• Weakness.

• Swelling in the arms and legs.

• Yellowish discoloration of the skin and eyes.

• Discomfort in the abdomen.

• Pain in the backbone.

• Vomiting.

• Decreased urinary output.

• Shortness of breath.

• Chest pain.

• Tightness around the waist.

• Increased heart rate.

• Coughing up of blood.

• Episodes of fainting.

• Numbness around the face.

• Swelling in the eye.

• Pain around the eyelids.

• Difficulty in seeing.

• Redness, warmth, itching, and tenderness at the site of injection.

• Joint pain.

What Is Emicizumab?

Emicizumab is an FDA-approved drug that is indicated in children, newborns, and even older patients, who are suffering from hemophilia A since it aids in bridging the clotting factors that aid in blood clots.

What Is the Composition of Emicizumab?

• Active Ingredients: Emicizumab.

• Inactive Ingredients: L-arginine, L-histidine, poloxamer 188, and L-aspartic acid.

What Is the Dosage of Emicizumab?

Emicizumab is available as a colorless or slightly yellow solution in a single-dose vial injection or several strengths which are- 30 mg/mL, 60 mg/0.4 mL, 105 mg/0.7 mL, and 150 mg/mL. The dosage is always prescribed by the healthcare professional.

What Are the Warnings That the Patient Must Consider While Undergoing Prophylaxis With Emicizumab?

• Patients who underwent Emicizumab prophylaxis were associated with the development of thromboembolism.

• Patients who underwent Emicizumab prophylaxis were associated with the development of thrombotic microangiopathy.