Advate

Name: Advate

Indications

Control And Prevention Of Bleeding Episodes

ADVATE [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] is an Antihemophilic Factor (Recombinant) indicated for control and prevention of bleeding episodes in adults and children (0-16 years) with Hemophilia A.

Perioperative Management

ADVATE is indicated in the perioperative management in adults and children (0-16 years) with Hemophilia A.

Routine Prophylaxis

ADVATE is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children (0-16 years) with Hemophilia A.

ADVATE is not indicated for the treatment of von Willebrand disease.

Overdose

No symptoms of overdose with ADVATE have been reported.

Side Effects of Advate

Serious side effects have been reported with Advate. See the "Advate Precautions" section.

Common side effects of Advate include the following:

  • cough
  • headache
  • joint pain
  • sore throat
  • fever
  • stomach pain
  • diarrhea
  • chills
  • runny nose or congestion
  • nausea or vomiting

This is not a complete list of Advate side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

 

Advate Interactions

No drug interactions have been studied by the manufacturer. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Advate Precautions

Serious side effects have been reported with Advate including the following:

Hypersensitivity Reactions. Advate can cause serious allergic reactions. Tell your healthcare provider immediately about any signs or symptoms of an allergic reaction, which include the following:

  • dizziness
  • numbness or tingling
  • rash
  • flushing
  • swelling in the face
  • hives
  • itching
  • trouble breathing
  • vomiting

Neutralizing antibodies. Your body may form inhibitors to factor VIII, known as antibodies. Antibodies are proteins made by the body as a natural part of the immune system in response to something it recognizes as foreign. If your form these inhibitors, Advate may not work properly. Your healthcare provider will monitor you for development of these inhibitors with blood tests.

Do not take Advate if you:

  • are allergic to Advate or to any of its ingredients
  • are allergic to mice or hamsters

Uses For Advate

Antihemophilic factor (AHF) injection is used to treat and prevent serious bleeding episodes in patients with a bleeding problem called hemophilia A. The bleeding episode may be related to an injury (trauma) or a surgical procedure. AHF is a protein that is produced naturally in the body. It helps the blood form clots to stop bleeding and prevents bleeding problems from happening as often.

Hemophilia A, also called classical hemophilia, is a condition where the body does not make enough AHF. If you do not have enough AHF and you become injured, your blood will not form clots properly. You might bleed into and damage your muscles and joints. AHF injection is given to increase the levels of AHF in the blood.

There are several different types of AHF. They are made from human blood or artificially by a man-made process (recombinant). AHF made from human blood has been treated and is not likely to contain harmful viruses, such as hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). The man-made AHF products do not contain these viruses.

This medicine is available only with your doctor's prescription.

Before Using Advate

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of antihemophilic factor injection in children.

No information is available on the relationship of age to the effects of Hemofil® M in the pediatric population. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of Advate®, Adynovate®, Eloctate™, Kogenate® FS, Kovaltry®, Novoeight®, and Xyntha® have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related medical problems, which may require caution and an adjustment in the dose for patients receiving Advate®, Adynovate®, Eloctate™, Kogenate® FS, Kovaltry®, Novoeight®, and Xyntha®.

No information is available on the relationship of age to the effects of antihemophilic factor injection in geriatric patients.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Antihemophilic Factor

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Antihemophilic Factor VIII (Recombinant) PegylatedAntihemophilic Factor (Recombinant) Porcine SequenceAntihemophilic Factor (Recombinant) Single ChainAntihemophilic Factor VIII (Recombinant)Antihemophilic Factor VIII Fc Fusion Protein Recombinant

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Allergy to hamster or mouse proteins, history of or
  • von Willebrand disease (blood clotting disorder)—Should not be used in patients with these conditions.
  • Heart or blood vessel disease—Use with caution. May make these conditions worse.

Precautions While Using Advate

It is very important that your doctor check you or your child closely while you are receiving this medicine to make sure it is working properly. Blood tests may be needed.

This medicine may cause serious types of allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Check with your doctor right away if you or your child has a rash, itching, hoarseness, trouble breathing, trouble swallowing, lightheadedness or dizziness, or any swelling of your hands, face, or mouth after you receive this medicine.

It is recommended that you carry an identification (ID) card or letter stating that you have hemophilia A and the type of medicine you are using. If you have any questions about what kind of identification to carry, check with your doctor.

Check with your doctor right away if you have any symptoms of parvovirus infection: fever, chills, drowsiness, runny nose, and followed by a rash or joint pain.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine is made from donated human blood. Some human blood products have transmitted certain viruses to people who have received them, although the risk is low. Human donors and donated blood are both tested for viruses to keep the transmission risk low. Talk with your doctor about this risk if you are concerned.

The stopper of the bottle (vial) contains dry natural rubber (a derivative of latex), which may cause allergic reactions in people who are sensitive to latex. Tell your doctor if you have a latex allergy before you start using this medicine.

How is this medicine (Advate) best taken?

Use Advate as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as a shot into a vein.
  • This medicine may be given at home.
  • If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
  • Follow how to use as you have been told by the doctor or read the package insert.
  • Wash your hands before and after use.
  • If stored in a refrigerator, let this medicine come to room temperature before mixing. Do not heat Advate.
  • This medicine needs to be mixed before use. Follow how to mix as you were told by the doctor.
  • Do not shake.
  • Most products will be clear and colorless after mixing. Some products may be clear to slightly cloudy and colorless after mixing. Some products may be colorless to a faint yellow after mixing. Be sure you know what the product will look like after mixing.
  • Do not use if the solution is cloudy, leaking, or has particles.
  • Do not use if solution changes color.
  • After mixing, do not refrigerate.
  • Use within 3 hours of making.
  • Throw away any part of opened vial not used after use.
  • Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

Advate Description

Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] is a purified glycoprotein consisting of 2,332 amino acids that is synthesized by a genetically engineered Chinese hamster ovary (CHO) cell line. In culture, the CHO cell line expresses recombinant antihemophilic factor (rAHF) into the cell culture medium. The rAHF is purified from the culture medium using a series of chromatography columns. The purification process includes an immunoaffinity chromatography step in which a monoclonal antibody directed against Factor VIII is employed to selectively isolate the rAHF from the medium. The cell culture and purification processes used in the manufacture of Advate employ no additives of human or animal origin. The production process includes a dedicated, viral inactivation solvent-detergent treatment step. The rAHF synthesized by the CHO cells has the same biological effects on clotting as Antihemophilic Factor (Human) [AHF (Human)]. Structurally the recombinant protein has a similar combination of heterogeneous heavy and light chains as found in AHF (Human).

Advate is formulated as a sterile, non-pyrogenic, white to off white powder for intravenous injection. Advate is available in single-dose vials that contain nominally 250, 500, 1000, 1500, 2000 and 3000 International Units (IU) per vial. When reconstituted with the appropriate volume of diluent, the product contains the following stabilizers in maximal amounts: 38 mg/mL mannitol, 10 mg/mL trehalose, 108 mEq/L sodium, 12 mM histidine, 12 mM Tris, 1.9 mM calcium, 0.15 mg/mL polysorbate-80, and 0.10 mg/mL glutathione. Von Willebrand Factor (vWF) is co-expressed with Factor VIII, and helps to stabilize it in culture. The final product contains no more than 2 ng vWF/IU rAHF, which will not have any clinically relevant effect in patients with von Willebrand's disease. The product contains no preservative.

Each vial of Advate is labeled with the rAHF activity expressed in IU per vial. Biological potency is determined by an in vitro assay, which employs a Factor VIII concentrate standard that is referenced to a World Health Organization (WHO) International Standard for Factor VIII concentrates. One IU, as defined by the World Health Organization standard for blood coagulation FVIII, human, is approximately equal to the level of FVIII activity found in 1 mL of fresh pooled human plasma. The specific activity of Advate is 4000 to 10000 IU per milligram of protein.

Nonclinical Toxicology

Single doses several fold higher than the recommended clinical dose (related to body weight) did not demonstrate any acute or toxic effect for Advate in laboratory animals (mouse, rat, rabbit, and dog). Multiple dose studies were not performed with Advate, but were preformed with the related product, RECOMBINATE and with formulation buffers of Advate.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been conducted with the active ingredient in Advate to assess its mutagenic or carcinogenic potential. The CHO cell line employed in the production of Advate is derived from that used in the biosynthesis of RECOMBINATE [Antihemophilic Factor (Recombinant)]. Advate has been shown to be comparable to RECOMBINATE with respect to its biochemical and physicochemical properties, as well as its non-clinical in vivo pharmacology.

RECOMBINATE was tested for mutagenicity at doses considerably exceeding plasma concentrations in vitro, and at doses up to ten times the expected maximal clinical dose in vivo. At that concentration, it did not cause reverse mutations, chromosomal aberrations, or an increase in micronuclei formation in bone marrow polychromatic erythrocytes. Studies in animals have not been performed to evaluate carcinogenic potential.

(web3)