Anti-Inhibitor Coagulant Complex: A Comprehensive Overview

Overview

Anti-inhibitor coagulant complex is a human plasma, dried and frozen with the bypassing activity of factor VII for intravenous administration (IV) or infusion after reconstitution. The complex is indicated for patients with hemophilia A (classic hemophilia caused by lack of clotting factor VIII) and B (Christmas disease caused by the lack of clotting factor IX), along with inhibitors. The anti-inhibitor coagulant complex got FDA (Food and Drug Administration) approval on 16 December 2013 to prevent bleeding episodes in hemophilia A and B patients. The article talks in detail about the uses, contraindications, side effects, warnings and precautions, pharmacological aspects, and drug interactions of this drug.

Drug Group:

Anti-inhibitor coagulant complex belongs to the drug class - Antifibrinolytics.

Indications

Anti-inhibitor coagulant complex is prescribed for hemophilia A and B with inhibitors for the following:

• Perioperative management.

• Control and prevention of bleeding episodes.

• Routine prophylaxis to reduce and prevent the frequency of bleeding episodes.

Dose Form and Strength:

• The drug is available in lyophilized (freeze-dried) powder in single-dose glass vials of 500, 1000, or 2500 units per vial.

For Patients:

What Is Hemophilia A?

It is a hereditary hemorrhagic disorder caused by the lack of blood clotting factor VIII, leading to excessive bleeding spontaneously or post-trauma. Hemophilia A causes joint bleeding followed by swelling and pain, bruising, blood in stool and urine, nosebleeds, urinary tract, gastrointestinal tract bleeding, prolonged bleeding after tooth extraction, cuts, or surgery, and bleeding without cause.

What Is Anti-inhibitor Coagulant Complex Prescribed For?

Anti-inhibitor coagulant complex is used to treat bleeding disorders, such as hemophilia A and B, with inhibitors for perioperative management, control and prevention of bleeding episodes, and routine prophylaxis to reduce and prevent the frequency of bleeding episodes.

What Precautions Should Be Followed Before Taking Anti-Inhibitor Coagulant Complex?

• A person should inform the doctor of any hypersensitivity reaction to the anti-inhibitor coagulant complex, its ingredients, or any other drug. They must report immediately any such symptoms to the healthcare provider if they occur after drug administration. If a person is allergic to latex, the doctor must be informed.

• There is a risk of hepatitis A (contagious liver infection caused by HAV or hepatitis A virus) or provirus B19 transmission and may experience symptoms such as chills, fever, drowsiness, and rhinorrhea (runny nose) accompanied by joint pain and rashes, two weeks later. A person may also experience hepatitis A infection symptoms, such as anorexia, low-grade fever, fatigue, nausea, dark urine, jaundice, abdominal pain, and vomiting. Therefore, in such cases, report to the healthcare provider immediately.

• One must also inform the doctor about any prescription or non-prescription drug that one is taking or planning to take before consuming the anti-inhibitor coagulant complex.

• In addition, one must also inform the healthcare provider about past and present medical history, such as thromboembolic diseases (in which the blot clots form within the vein and later get dislodged into the blood) and cardiovascular diseases (heart and circulatory diseases).

• A person who is pregnant or planning to conceive or breastfeed must also inform the doctor before starting with the anti-inhibitor coagulant complex.

What Is the Drug Dosage of Anti-inhibitor Coagulant Complex?

Adult and Pediatric Drug Dosage: (Hemophilia A and B)

1. Perioperative Management:

• Preoperative: Immediately before surgery, 50 to 100 units per kilogram (kg) intravenously (IV) is given once.

• Postoperative: 50 to 100 units per kilogram intravenously, six to 12 hours is given until bleeding and healing are achieved.

2. Prevention and Bleeding Control

• Severe Hemorrhage: For example, in central nervous system bleeding, 100 units per kilogram (kg) is given intravenously for about six to 12 hours. The drug dosage should be at most 200 units per kg per day unless the severity of the bleeding justifies it.

• Joint Hemorrhage: 50 units per kilogram after every 12 hours; later, increasing to 100 units per kg every 12 hours is recommended until the clinical signs are improved. The dosage should not exceed 200 units per kg per day.

• Soft Tissue Hemorrhage: 100 units per kilogram IV every 12 hours, not exceeding the dosage beyond 200 units per kg per day.

3. Routine Prophylaxis:

• 85 units per kilogram intravenously every alternate day is given.

What Are the Side Effects of Anti-inhibitor Coagulant Complex?

Common Side Effects:

• Chills.

• Fever.

• Headache.

• Pain around the needle prick.

• Change in heart rate and blood pressure.

• Flushing.

• Numbness and tingling sensation around the face area.

• Dark-colored urine.

• Shortness of breath.

• Vomiting.

• Nausea.

• Cough or wheezing.

• Dizziness.

Serious Side Effects:

• Severe cough.

• Chest pain.

• Joint pain and rash.

• Trouble breathing.

• Sudden weakness.

• Hoarseness.

• Hives.

• Slurred speech.

• Tremors and profuse sweating.

• Loss of coordination.

• Blurred vision.

• Swelling and pain in the eye.

• Lightheadedness.

Overdose:

Acute Overdose

High doses of anti-inhibitor coagulant complex can cause the risk of developing pulmonary embolism (blot clot in the arteries supplying blood to the lungs), myocardial infarction (heart attack), venous thrombosis (blockage of a vein due to clot formation), and disseminated intravascular coagulation (DIC).

Chronic Overdose

There is no information available regarding the chronic drug overdose of anti-inhibitor coagulant complexes.

Drug Storage and Disposal:

Anti-inhibitor coagulant complex is stored at 2 to 25 degrees Celsius or 26 to 77 degrees Fahrenheit. It should be stored in its original package to protect it from light and not frozen. However, if refrigerated, allow the vials to reach room temperature before preparation and reconstitution.

Expired or unused drugs or reconstitution, as well as used needles and syringes, should be disposed of cautiously as per the local garbage disposal laws or by contacting the local pharmacist for safe drug disposal methods. In addition, used syringes and needles can be discarded using puncture-proof sharp disposal containers.

The drug and the puncture-proof container must be kept out of reach of children.

For Doctors:

What Are the Pharmacological Actions of Anti-inhibitor Coagulant Complex?

Clinical Pharmacology

• Mechanism of Action: Anti-inhibitor coagulant complex induces and facilitates thrombin generation to control bleeding. The drug contains activated factor VIII and non-activated factors II, IX, and X, which can interact with platelets and plasma coagulation factors, leading to hemostasis by increasing impaired thrombin generation with inhibitors.

• Pharmacodynamics: The anti-inhibitor coagulant complex contains various clotting factors promoting thrombosis by acting at several coagulation processes.

• Pharmacokinetics: The pharmacokinetics of the Anti-inhibitor coagulant complex have yet to be established in humans. However, the coagulation factors present in the drug are increased following intravenous administration within 10 to 30 minutes, and each clotting factor has varying half-lives. The half-life of factor VIII is five hours, factor X is 40 hours, prothrombin is 65 hours, and factor IX is 25 hours.

Ingredients

• Active Ingredients: Activated factor VIII.

• Inactive Ingredients: Non-activated factor II, IX, X.

Drug Administration and Monitoring

Administration:

• The drug is administered slowly through intravenously (IV) injection or IV infusion after reconstitution only.

• The drug dosage and treatment duration usually depend on the extent and location of bleeding and the patient’s clinical status. Monitoring the replacement therapy is important in case of any major surgery and fatal bleeding episodes.

Reconstitution:

• The entire reconstitution process should be done with an aseptic technique.

• In case of refrigeration, the sterile water for injection of diluent and the Anti-inhibitor coagulant complex vial should be allowed to reach room temperature,

• The cap of the diluent vials and concentrate should be removed.

• Sterile alcohol swabs should be used to wipe the stoppers of both vial and diluent, and they should be allowed to dry before use.

• The high-flow device devices for administering this drug should be opened without touching its lid.

• Next, place the diluent on some plane, solid, and flat surface, and insert the spike via the diluent stopper without touching the clear spike.

• Grip the device at the edge of the package and remove it without removing the cap (yellow) over the high-flow device and the purple spike.

• The device should be turned upside down to place the diluent on top, and then the spike (purple) should be quickly installed directly on the vial. The vacuum draws the diluent into the drug vial.

• The connection between the two vials should be cautiously established by closing the open fluid pathway during the spike's initial insertion into the vial (diluent).

• The vial should be gently swirled to dissolve the Anti-inhibitor coagulant complex drug completely.

• The prepared reconstitution should be administered within three hours and must not be refrigerated. The unused vial should be discarded safely.

Monitoring:

• The doctor should advise the patient for a platelet count test if expected treatment outcomes are not achieved or during the initial use of this drug. The effectiveness of this drug requires a functionally intact platelet count.

• There is no direct measure of the drug’s efficacy available, and various coagulation tests, aPTT (activated partial thromboplastin time), or WBCT (whole blood clotting test), also do not relate to the clinical outcomes. Therefore, increasing the drug dosage is not recommended because drug overdose can produce disseminated intravascular coagulation (DIC), a condition that affects blood’s ability to form clots and cease bleeding.

What Are the Contraindications of Anti-Inhibitor Coagulant Complex?

Contraindications of Anti-inhibitor coagulant complex:

• The drug is contraindicated in case of severe hypersensitivity or anaphylactic reactions to an Anti-inhibitor coagulant complex, any of its components, or any other drug.

• Acute embolism or thrombosis, which includes myocardial infarction.

• Disseminated intravascular coagulation (DIC).

What Are the Drug Interactions of Anti-Inhibitor Coagulant Complex?

• Anti-inhibitor coagulant complexes can cause thromboembolic events, such as myocardial infarction, pulmonary embolism, venous thrombosis, and stroke in patients with thrombotic risk factors and following the administration of high dosage. In addition, thrombotic events can also occur in patients with disseminated intravascular coagulation (DIC), septicemia, atherosclerosis disease, crush injury, or treatment with recombinant factor VIIa due to predisposing coagulopathy or circulating factors. Therefore, the potential benefits of the treatment with the anti-inhibitor coagulant complex should be established against the potential risk of thromboembolic events in a patient.

• Anti-inhibitor coagulant complex has a risk of carrying infectious agents, such as Creutzfeldt-Jakob disease - a degenerative brain disorder that causes dementia and death- (vCJD) agent, and viruses, as it is prepared from human plasma. However, the plasma donors are screened for any exposure to infections, and the infectious agents are eliminated during the manufacturing; still, the risk of such agents in the drug is present. Therefore, the drug should be cautiously prescribed, keeping in mind all the risks of infectious human pathogen agents present in the drug, and the same should be conveyed to the patient and the attendant.

• The drug is also known to cause anaphylactic, allergic, and hypersensitivity reactions after infusion.A patient may present symptoms of gastrointestinal issues, urticaria (bronchospasm, angioedema, and hypotension), and hypotension (low blood pressure). In addition, other reactions of hypersensitivity include pyrexia, chills, and hypertension. Therefore, if any symptoms of severe hypersensitivity reactions occur in a patient, the drug should be immediately stopped, and supportive care should be started.

• The drug may also interfere with laboratory tests as it contains iso hemagglutinins, anti-A and anti-B, which can interfere with serological tests, such as the Coombs test or antiglobulin test for red cell antibodies.

Drug Interactions of Anti-Inhibitor Coagulant Complex:

Anti-inhibitor coagulant complex is not recommended to be prescribed concomitantly with certain drugs. Healthcare providers should adjust the dosage and how the patient uses both drugs. These drugs include:

• Emicizumab.

• Aminocaproic acid.

• Tranexamic acid.

• Coagulation factor VIIa.

There should be at least more than 12 hours of gap between the discontinuation of these drugs and the initiation of the anti-inhibitor coagulant complex.

Use in Special Populations:

Pregnancy

Drug-associated risks with anti-inhibitor coagulant complex have not yet been studied in pregnant women. Also, no data or studies are available on the drug's effects on animal reproduction. There is no information regarding the fetal harm or reproduction effects caused by the drug, and no studies show any impact on labor and delivery as well. According to the United States population, the risks associated with birth defects and miscarriages are approximately two to four percent and 15 to 20 percent, respectively. Therefore, the drug should be prescribed to this population only if the potential benefits of the drug outweigh the potential benefits in pregnancy cases.

Lactation: No clinical studies or data show any presence of the drug in human milk, its effects on milk production, or its effects on breastfed babies. However, the health and developmental effects of the drug on the mother and the baby should be cautiously evaluated.

Pediatric Use: The drug's safety and efficacy in pediatric patients have been established, and the results have been excellent, showing hemostasis in the majority of cases. However, the same has not yet been established in neonates. There, doctors should prescribe the drug cautiously.

Geriatric Use: The effectiveness and safety of the drug in the geriatric population greater than or equal to 65 years has not been established yet. Therefore, the drug should be cautiously prescribed for this population.