Nonacog Beta Pegol - A Brief Overview

Overview

A novel pharmaceutical drug, Nonacog beta pegol, is the brainchild of Novo Nordisk A/S, Denmark. It contains PEGylated recombinant human factor IX and has a molecular weight of approximately 98kDa. It has an excellent extended terminal half-life and is administered intravenously. Its therapeutic safety and efficacy have been demonstrated in the phase 3 Paradigm trials that comprised previously treated hemophiliac B adolescents and adults. Nonacog beta pegol is used to cease bleeding and prevent bleeding via prophylaxis treatment in hemophilic patients. Although this drug is associated with allergic reactions in certain individuals, it has proven to improve the quality of life in most hemophilic patients.

How Does Nonacog Beta Pegol Work?

Nonacog beta pegol helps replenish the body with factor IX (also known as the Christmas factor) when it fails to produce it via its normal pathways. Although it is a synthetic substance, it functions in the same manner as factor IX does and helps in blood clotting.

Uses

Nonacog beta pegol is used in the following ways :

• To stop bleeding in hemophilic B patients (12 years and above).

• To prevent bleeding in hemophilic B patients (12 years and above).

Dosage and Administration

The dosage of Nonacog beta pegol varies, depending on its use for various medical situations.

• For Ceasing Bleeding: Typically, a dose of 40 international units or 40 IU per kg of body weight is prescribed to the patients, but the dose can be increased to 80 IU per kg of body weight, depending on the patient's requirements.

• For Prophylaxis Treatment to Prevent Bleeding: 40 international units or 40 IU per kg of body weight, administered weekly. However, the dosage can change depending on the patient's needs.

Missed Dose: Patients should contact their doctors about missing a scheduled dose so that the consequent dose can be administered.

Warnings and Precautions

• There is a rare risk of allergic reactions to Nonacog beta pegol. When this happens, patients can elicit a variety of signs and symptoms, ranging from a skin rash to breathlessness. Hence, patients on Nonacog beta pegol should be monitored regularly.

• Patients with a central venous access device (CVAD) or who are on catheters are prone to infections and blood clots following the administration of Nonacog beta pegol.

• Patients who have had recent surgery or suffer from severe medical conditions (such as heart disease, liver disease, cancer, etc.) tend to develop blood clots following the administration of Nonacog beta pegol.

• Patients having risk factors such as elevated blood pressure, tobacco abuse, and obesity are also susceptible to the formation of blood clots when administered with Nonacog beta pegol.

Use in Specific Populations

1. Kidney Disease: Certain studies have reported rare incidences of the development of nephrotic syndrome following the administration of Nonacog beta pegol in hemophilic patients. Hence, physicians should regularly monitor the kidney function of patients receiving the drug.

2. Pregnancy: If patients are pregnant or plan on getting pregnant soon, they should discuss these facts with their physician before starting the therapy with Nonacog beta pegol.

3. Lactation: Lactating women should consult a physician before starting therapy with Nonacog beta pegol to ensure its safety for both the mother and the baby.

4. Allergies: Nonacog beta pegol tends to initiate allergic reactions in certain individuals. Hence, when the Nonacog beta pegol therapy starts, physicians should give the first dose in a clinic or hospital and keep the patient under observation for at least a day to ensure patient safety. Also, if patients develop symptoms like swelling of lips, mouth, and tongue, breathlessness, chest tightness, and hives, they should rush to the hospital.

5: Pediatric: Nonacog beta pegol is not safe for pediatric use. It should be only administered to adolescents (at least 12 years old) and adults.

Drug Interactions:

Formal drug interaction studies are typically not applicable to Nonacog beta pegol and other coagulation factors.

For Patients

What Is Hemophilia B?

Hemophilia B, also known as Christmas disease, is a bleeding disorder in which affected individuals tend to bleed longer than their counterparts. This is primarily because these individuals lack an essential clotting factor - factor IX, otherwise known as the Christmas factor. In most cases, this deficiency is passed down to children from parents, but about one-third of the hemophilic cases arise due to genetic mutations. Hemophilia B is less common than hemophilia A, a bleeding disorder characterized by the deficiency of clotting factor VIII. The signs and symptoms vary from one individual to another, depending on the severity of hemophilia B. It could be mild, moderate, or severe.

How Does Nonacog Beta Pegol Work?

Nonacog Beta Pegol is a synthetic form of the Christmas factor (also known as factor IX). It replaces the deficient factor, helping initiate a series of cascade factors that help blood clotting.

Dosage and Administration:

The dosage of Nonacog beta pegol varies, depending on its use for various medical situations. It is administered intravenously with the following doses.

• For Ceasing Bleeding: Typically, a dose of 40 international units or 40 IU per kg of body weight is prescribed to the patients, but the dose can be increased to 80 IU per kg of body weight, depending on the patient's requirements.

• For Prophylaxis Treatment to Prevent Bleeding: 40 international units or 40 IU per kg of body weight, administered weekly. However, the dosage can change depending on the patient's needs.

Missed Dose: Patients should contact their doctors about missing a scheduled dose so that the consequent dose can be administered.

What Must Special Dietary Instructions Be Followed?

Unless advised otherwise, no dietary changes are required.

How Is Nonacog Beta Pegol Used?

• The physician calculates the dosage and frequency of administration, and it varies from case to case. The dosage is calculated as per the patient's weight and age.

• The doses should be administered as per the doctor's advice, and patients should consult a doctor before modifying or ceasing the use of the drug.

• After reconstituting the powder with the solvent, Nonacog beta pegol should be injected intravenously, ensuring aseptic techniques.

• After its reconstitution, the solution should appear clear to colorless or slightly yellow but is always free of any visible particles.

• If the solution is cloudy, immediately discard it.

How Is Nonacog Beta Pegol Stored?

1. Unopened Nonacog Beta Pegol:

• When unopened, Nonacog beta pegol is a highly stable drug with a shelf life of at least two years when stored between 2 to 8 degrees Celsius (refrigeration).

• It can also be stored in environments having a temperature of 30 degrees Celsius, but its shelf life decreases to six months.

• Once taken out of the refrigerator, it should not be placed inside the refrigerator again.

• The vial should always be placed in its original packaging to prevent oxidation and deterioration from the sunlight.

2. Reconstituted Nonacog Beta Pegol:

• After reconstitution, Nonacog beta pegol should be used immediately.

• If it is not used immediately, it can be stored for four hours when stored at room temperature (with a maximum temperature of 30 degrees Celsius) or for 24 hours when refrigerated between two and eight degrees Celsius.

How Is Nonacog Beta Pegol Discarded?

After administration, the syringe and its infusion needle, vial, and vial adapter should be safely discarded. The disposal of Nonacog beta pegol should be under local guidelines and medical regulatory bodies. If not expired, unneeded medicines can also be returned to the pharmacist.

What Are the Side Effects of Nonacog Beta Pegol?

The side effects of Nonacog beta pegol include:

• Pruritis.

• Skin reaction at the site of administration.

• Nausea.

• Vomiting.

• Fatigue.

• Heart palpitations.

• Hot flushes.

Occasionally, the side effects can be severe. The following side effects are uncommon; however, the doctor must be informed immediately if these side effects occur -

• Difficulty in swallowing.

• Difficulty in breathing.

• Wheezing.

• Shortness of breath.

• Swelling of the lips, tongue, face, and hands.

• Skin rash, hives.

• Itchy skin.

• Cold and pale skin.

• Chest discomfort or chest tightness.

• Decreased blood pressure.

• Fast, irregular heartbeats.

• Loss of consciousness.

What Should Be Informed to the Healthcare Provider Before Using Nonacog Beta Pegol?

Patients should ensure the following before starting the doses of Nonacog beta pegol:

• They should inform the doctor of any previous history of allergies associated with the Nonacog beta pegol, its excipients, or any other medication.

• Patients should share their medical history and inform the physician of all the prescription and non-prescription medications they might be taking.

• Patients should inform the physician about a history of serious medical conditions such as - heart diseases (heart attack, angina, hypertension, heart failure), liver diseases, cancer, etc.

• Patients should also inform about the history of recent surgeries since this drug can make an individual susceptible to thromboembolic events.

• Patients who are pregnant or planning on becoming pregnant in the immediate future should disclose this information to their doctors before starting the therapy with Nonacog beta pegol.

For Doctors

Indications

• To stop bleeding.

• As a prophylaxis treatment to prevent bleeding.

Contraindications:

The following groups should avoid the use of this medication-

• Individuals with known allergies to hamster proteins.

• Individuals having hypersensitivity to Nonacog beta pegol and the following excipients -

1. Sodium chloride.

2. Histidine.

3. Sucrose.

4. Polysorbate 80.

5. Mannitol.

6. Sodium hydroxide.

7. Hydrochloric acid.

Constituents:

Active Component - Nonacog beta pegol.

Excipients -

Powder:

• Sodium chloride.

• Histidine.

• Sucrose.

• Polysorbate 80.

• Mannitol.

• Sodium hydroxide (for pH adjustment)

• Hydrochloric acid (for pH adjustment).

Solvent:

• Histidine.

• Water for injection.

• Sodium hydroxide(for pH adjustment).

• Hydrochloric acid (for pH adjustment).

Pharmacology

Mechanism of Action:

Factor IXa and tissue complex factor VII together activate Nonacog beta pegol, cleaving the peptide and the 40 kDa PEG moiety. This activation process results in the formation of recombinant factor IX, which has the same biological activity as endogenous coagulation factor IXa. Activating factor VIIIa and factor IX initiates a mechanism that triggers the coagulation cascade, involves factor X, and converts prothrombin into thrombin. Thrombin formation leads to the conversion of fibrinogen into fibrin, aiding clot formation.

The Half-Life of Nonacog Beta Pegol - The half-life of Nonacog beta pegol varies for adults and children. In children, at a steady state, it is estimated to be 70 hours, whereas, for adults, it is 89 hours.

Dosage and Administration:

Administered intravenously, the dosage of Nonacog beta pegol varies, depending on its use for various medical situations.

• For Ceasing Bleeding: Typically, a dose of 40 international units or 40 IU per kg of body weight is prescribed to the patients, but the dose can be increased to 80 IU per kg of body weight, depending on the patient's requirements.

• For Prophylaxis Treatment to Prevent Bleeding: 40 international units or 40 IU per kg of body weight, administered weekly. However, the dosage can change depending on the patient's needs.

Missed Dose: Patients should contact their doctors about missing a scheduled dose so that the consequent dose can be administered.

Adverse effects of Nonacog Beta Pegol:

The adverse effects of Nonacog beta pegol include:

• Pruritis.

• Skin reaction at the site of administration.

• Nausea.

• Vomiting.

• Fatigue.

• Heart palpitations.

• Hot flushes.

• Anaphylaxis.

Pharmacokinetics of Nonacog Beta Pegol:

1. Absorption - Following an intravascular dose, Nonacog beta pegol shows a terminal half-life of 41 hours to 67 hours.

2. Distribution - Nonacog beta pegol rarely accumulates in the tissues, and following its administration, the mean volume of distribution at a steady state is 64 ml/kg. The distribution of Nonacog beta pegol varies according to the age of the patient.

Following a single dose, the volume of distribution varies in the following manner in different groups-

• Children Less Than 6 Years of Age - 72ml/kg

• Adolescents Between the Ages of 7 and 12 Years - 68ml/kg

• Adolescents Between the Ages of 13 and 17 Years - 59ml/kg

• Adults - 47ml/kg

3. Metabolism - Nonacog beta pegol's protein components are broken down into simpler forms by the activity of endosomes and lysosomes. In contrast, the PEG component of the drug returns to circulation, thereby increasing its retention in the body by 7.5 to 9 times more than the original compound.

4. Elimination - The PEG component of Nonacog beta pegol, measuring 40 kDa, is primarily excreted and eliminated via the feces and urine, constituting 40 percent and 49 percent of the initial dose. In contrast, a bi-phasic elimination process eliminates the PEG part of Nonacog beta pegol.