Advate

Name: Advate

Advate Dosage

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended. Always check the strength of the medicine on the label to be sure you are using the correct potency.

Recombinant antihemophilic factor is injected into a vein through an IV. You may be shown how to use an IV at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of needles, IV tubing, and other items used.

Recombinant antihemophilic factor is usually given every 8 to 24 hours for 1 to 4 days, depending on the reason you are using the medicine.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Always wash your hands before preparing and giving your injection.

Recombinant antihemophilic factor must be mixed with a liquid (diluent) before injecting it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

After mixing the medicine and diluent, keep the mixture at room temperature and use it within 3 hours. Do not put mixed medicine into a refrigerator.

Prepare your dose in a syringe only when you are ready to give yourself an injection. Each vial is for one use only. After measuring your dose, throw the vial away, even if there is medicine left in it.

Do not use recombinant antihemophilic factor if it has changed colors or has particles in it. Call your pharmacist for new medication.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

While using recombinant antihemophilic factor, you may need frequent blood tests.

Your body may develop antibodies to antihemophilic factor, making it less effective. Call your doctor if this medicine seems to be less effective in controlling your bleeding.

Store the medicine and the diluent in their original container in the refrigerator. Do not allow them to freeze. Take the medicine out of the refrigerator and allow it to reach room temperature before injecting your dose.

You may also store the medication and diluent at room temperature until the expiration date on the label. Some brands of this medicine can be stored at room temperature for only a certain number of months, or until the expiration date (whichever comes first). Follow the storage directions on the medicine label.

If you store this medicine at room temperature, do not return it to the refrigerator.

Do not store this medicine in bright light. Throw away any leftover medicine and diluent if the expiration date has passed.

Wear a medical alert tag or carry an ID card stating that you have hemophilia. Any doctor, dentist, or emergency medical care provider who treats you should know that you have a bleeding or blood-clotting disorder.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Since recombinant antihemophilic factor is used when needed, you may not be on a dosing schedule. If you are on a schedule, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Uses

This medication is used to control and prevent bleeding episodes in people with low levels of factor VIII (hemophilia A). It is also used in these patients before surgery to prevent bleeding. People with low factor VIII levels are at risk for bleeding longer after an injury/surgery and for bleeding inside the body (especially into the joints and muscles). This product contains a man-made form of factor VIII, also called antihemophilic factor. This product is used to temporarily replace the missing factor VIII, a protein (clotting factor) that is normally in the blood, so that the blood can clot and the bleeding can stop.This medication should not be used to treat von Willebrand disease.

Warnings

Included as part of the PRECAUTIONS section.

Inform MD

Before taking Advate, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to Advate or to any of its ingredients
  • have or have had any medical problems
  • are allergic to mice or hamsters
  • have been told that you have inhibitors to factor VIII
  • are pregnant or plan to become pregnant
  • are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Other Requirements

  • Keep all appointments with your doctor and laboratory. Your doctor will order lab tests to check your levels of factor VIII to determine your dose and frequency of Advate.

Proper Use of antihemophilic factor

This section provides information on the proper use of a number of products that contain antihemophilic factor. It may not be specific to Advate. Please read with care.

A doctor or other trained health professional will give you or your child this medicine in a hospital or clinic setting. This medicine is given through a needle placed in one of your veins.

This medicine may also be given at home to patients who do not need to be in a hospital or clinic. If you or your child is using this medicine at home, your doctor will teach you how to prepare and inject the medicine. Make sure you understand all of the instructions before giving yourself an injection. Your dose may change based on where you are bleeding. Do not use more medicine or use it more often than your doctor tells you to.

Use only the brand of this medicine that your doctor prescribed. Not all brands are prepared in the same way and the dose may be different.

Every package of medicine comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

To prepare the medicine using 2 bottles (vials) or containers:

  • Take the bottles of powder medicine and liquid (diluent) out of the refrigerator and warm them to room temperature.
  • Wipe the rubber surface of the bottles with an alcohol swab and allow them to dry.
  • Follow the specific directions for your brand of medicine when you prepare the injection.
  • Add the liquid to the powder using the special transfer needle or transfer device that comes with the package.
  • When injecting the liquid into the dry medicine, aim the stream of liquid against the wall of the container of dry medicine to prevent foaming.
  • Swirl the bottle gently to dissolve the medicine. Do not shake the bottle. Shaking will create foam in the mixture.
  • Check the mixture to make sure it is clear. Do not use the medicine if you can see anything solid in the mixture or if the mixture is cloudy.
  • Use a plastic disposable syringe to remove the mixture from the bottle. Use a special filter needle if your brand of medicine provides one.
  • Give the injection as directed by your doctor.
  • If you are using more than one bottle of medicine for your dose, prepare the second bottle the same way. Add the mixture from the second bottle to the same syringe.

To prepare the medicine using a prefilled dual-chamber syringe (Xyntha®):

  • Take the prefilled dual-chamber syringe out of the refrigerator and warm it to room temperature.
  • The dual-chamber syringe has the powder medicine in one part and the liquid (diluent) in the second part of the syringe.
  • Attach the plunger rod to the syringe according to the directions. Keep the syringe pointed up to prevent leaking of the liquid.
  • Remove the white seal and the grey rubber tip cap. Put the blue vented cap on the syringe. Do not touch the open ends of the syringe and the blue cap.
  • Slowly push the plunger until the 2 stoppers inside the syringe are together. This will push all of the liquid into the chamber with the powder medicine.
  • Keep the syringe pointed up and gently swirl the syringe to mix the liquid and powder.
  • Check the mixture to make sure it is clear. Do not use the medicine if you can see anything solid in the mixture or if the mixture is cloudy.
  • Keep the syringe pointed up and push the plunger until most of the air is removed.
  • A special infusion set comes with the package. Remove the blue cap and attach the infusion set to the syringe.
  • Give the injection as directed by your doctor.
  • If you are using more than one syringe of medicine for your dose, prepare the second dual-chamber syringe the same way. The mixture from each syringe will be combined together in a separate syringe before your injection. Your doctor will show you how to do this.

Use the mixture within 3 or 4 hours after it is prepared. It must not be stored and used later. Do not put the mixture in the refrigerator.

Do not reuse syringes and needles. Put used syringes and needles in a puncture-resistant disposable container, or dispose of them as directed by your doctor.

Talk to your doctor before traveling. You should plan to bring enough medicine for your treatment when traveling.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For injection dosage form (injection):
    • For bleeding episodes in patients with hemophilia A:
      • Adults and teenagers—Dose is based on body weight and the type of bleeding episode. The dose must be determined by your doctor.
      • Children—Dose is based on body weight and the type of bleeding episode. The dose must be determined by your child's doctor.

Missed Dose

Call your doctor or pharmacist for instructions.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

The AHF products should be stored in the original container in the refrigerator. Do not let the packages freeze. They can also be kept at room temperature for short periods of time, such as 3 to 12 months. Store the medicine as directed by your doctor or by the manufacturer of the brand you are using. Protect the container from heat and direct light.

If you move the medicine from the refrigerator to room temperature, write the date you take it from the refrigerator on the container. The length of time the medicine can remain at room temperature will depend on the brand you use. If you have already stored the medicine at room temperature, do not return it to the refrigerator. If you do not use the medicine within the time recommended by the manufacturer, you must destroy the medicine.

Advate Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Fever
Less common or rare
  • Changes in facial skin color
  • chills
  • fast or irregular breathing
  • nausea
  • puffiness or swelling of the eyelids or around the eyes
  • sensation of burning, warmth, heat, numbness, tightness, or tingling
  • skin rash, hives, or itching
  • tightness in the chest
  • troubled breathing
  • unusual tiredness or weakness
Incidence not known
  • Bluish color of the fingernails, lips, skin, palms, or nail beds
  • blurred vision
  • chest pain or discomfort
  • confusion
  • cough
  • deep or fast breathing with dizziness
  • difficult or labored breathing
  • difficulty with swallowing
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fast, pounding, or irregular heartbeat or pulse
  • noisy breathing
  • numbness of the feet, hands, and around the mouth
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • slow or irregular heartbeat
  • sweating
  • swelling of the face, throat, or tongue
  • unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Headache
Less common
  • Burning, stinging, or swelling at the injection site
  • diarrhea
  • dizziness or lightheadedness
  • dry mouth or bad taste in the mouth
  • lack or loss of strength
  • nosebleed
  • redness of the face
  • vomiting
Rare
  • Change in taste
  • loss of taste
Incidence not known
  • Abdominal or stomach pain
  • feeling of warmth
  • increased sweating
  • irritability
  • muscle or bone pain
  • redness of the eye
  • redness of the face, neck, arms, and occasionally, upper chest
  • redness of the skin
  • trouble seeing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

What are some other side effects of Advate?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Irritation where the shot is given.
  • Headache.
  • Cough.
  • Nose and throat irritation.
  • Joint pain.
  • Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Advate or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Advate (antihemophilic factor (recombinant) (advate)). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Advate Dosage and Administration

For Intravenous Use After Reconstitution only

  • Treatment with Advate should be initiated under the supervision of a physician experienced in the treatment of hemophilia A.
  • Each vial of Advate has the recombinant Factor VIII potency in international units stated on the label. The expected in vivo peak increase in Factor VIII level expressed as IU/dL of plasma or percent normal can be estimated by multiplying the dose administered per kg body weight (IU/kg) by 2.
  • The dosage and duration depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the patient's clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes. [Control and Prevention of Bleeding Episodes (2.1) and Perioperative Management (2.2)]

The expected in vivo peak increase in Factor VIII level expressed as IU/dL (or % of normal) can be estimated using the following formulas:

IU/dL (or % of normal)=[Total Dose (IU)/body weight (kg)] × 2 [IU/dL]/[IU/kg]

OR

Dose (IU) = body weight (kg) × Desired Factor VIII Rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL)

Examples (assuming patient's baseline Factor VIII level is < 1% of normal):

  1. A dose of 1750 IU Advate administered to a 70 kg patient should be expected to result in a peak post-infusion Factor VIII increase of 1750 IU × {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal).
  2. A peak level of 70% is required in a 40 kg child. In this situation, the appropriate dose would be 40 kg × 70 IU/dL/{[2 IU/dL]/[IU/kg]} = 1400 IU.

The dose and frequency of administration should be based on the individual clinical response. Patients may vary in their pharmacokinetic (e.g. half-life, in vivo recovery) and clinical responses to Advate. Although you can estimate the dose by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests including serial Factor VIII activity assays be performed  [see WARNINGS and PRECAUTIONS: Monitoring Laboratory Tests (5.4) and Pharmacokinetics (12.3)].

Control and Prevention of Bleeding Episodes

A guide for dosing in the treatment of bleeding episodes is provided in Table 1. The careful control of treatment dose is especially important in cases of life-threatening episodes.

Table 1 Guide to Advate Dosing for Treatment of Bleeding Episodes in Adults and Children
* Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Degree of Hemorrhage
Or
Type of Bleeding Episodes
Required Peak Post-infusion Factor VIII Activity in the Blood
(as % of Normal or IU/dL)
Dosage and Frequency Necessary to Maintain the Therapeutic Plasma Level
Minor
Early hemarthrosis, mild muscle bleeding, or mild oral bleeding episode.
20-40 10-20 IU/kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for one to three days until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved.
Moderate
Moderate bleeding into muscles, bleeding into the oral cavity, definite hemarthroses, and known trauma.
30-60 15-30 IU per kg* Repeat infusions every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for three days or more until the bleeding episode is resolved (as indicated by relief of pain) or healing is achieved.
Major
Significant gastrointestinal bleeding, intracranial, intra-abdominal or intrathoracic bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, Fractures, Head trauma.
60-100 Initial dose 30-50 IU per kg:
Repeat dose 30-50 IU per kg every 8 to 24 hours (6 to 12 hours for patients under the age of 6) until resolution of the bleeding episode has occurred.

Peri-operative Management

A guide for dosing in perioperative management is provided in Table 2. The careful control of dose and duration of treatment is especially important in cases of major surgery or life-threatening bleeding episodes.

Table 2 Guide to Advate Dosing for Perioperative Management in Adults and Children
Type of Surgery Required Peak Post-infusion Factor VIII Activity in the Blood
(% of Normal or IU/dL)
Frequency of Infusion
* Dose (IU/kg) = Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)

Minor

Including tooth extraction

60-100 A single bolus infusion (30-50 IU/kg*) beginning within one hour of the operation. Optional additional dosing every 12 to 24 hours as needed to control bleeding. For dental procedures, adjunctive therapy may be considered.

Major

Examples include intracranial, Intra-abdominal, or Intrathoracic surgery, joint replacement surgery

80-120
(pre- and post-operative)
Preoperative bolus infusion: 40-60 IU/kg*. Verify 100% activity has been achieved prior to surgery. Maintenance bolus infusion (40-60 IU/kg*) repeat infusions every 8 to 24 hours (6 to 24 hours for patients under the age of 6), depending on the desired level of Factor VIII and state of wound healing.

Instruction for Use

Advate is administered by intravenous (IV) injection after reconstitution. Patients should follow the specific reconstitution and administration procedures provided by their physicians.

For instructions, patients should follow the recommendations in the FDA-approved patient labeling.

Reconstitution, product administration, and handling of the administration set and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single use. Discard all equipment, including any reconstituted Advate in an appropriate container.

Preparation and Reconstitution:

The procedures below are provided as general guidelines for the reconstitution and administration of Advate. Always work on a clean surface and wash your hands before performing the following procedures.

  1. Bring the Advate (dry factor concentrate) and Sterile Water for Injection, USP (diluent) to room temperature.
  2. Remove caps from the factor concentrate and diluent vials.
  3. Cleanse stoppers with germicidal solution, and allow to dry prior to use. Place the vials on a flat surface.
  4. Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package.
  5. Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B).
  6. Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike.
  7. Turn the system over, so that the diluent vial is on top. Quickly insert the white plastic spike fully into the Advate vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the Advate vial.
  8. Swirl gently until Advate is completely dissolved.

Do not refrigerate after reconstitution.

Administration

Advate is intended for intravenous use after reconstitution only.

  • Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless in appearance. If not, do not use the solution and notify Baxter immediately.
  • Administer Advate at room temperature not more than 3 hours after reconstitution.
  • Plastic syringes must be used with this product, since proteins such as Advate tend to stick to the surface of glass syringes.
  1. Use aseptic technique.
  2. Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device (Figure E). DO NOT INJECT AIR.
  3. Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure F).
  4. Disconnect the syringe; attach a suitable needle and inject intravenously as instructed under Administration by Bolus Infusion.
  5. If a patient is to receive more than one vial of Advate, the contents of multiple vials may be drawn into the same syringe. Please note that the BAXJECT II device is intended for use with a single vial of Advate and Sterile Water for Injection only, therefore reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device.

Administration by bolus infusion

Administer a dose of Advate over a period of ≤ 5 minutes (maximum infusion rate, 10 mL/min). Determine the pulse rate before and during administration of Advate. Should a significant increase in pulse rate occur, reducing the rate of administration or temporarily halting the injection usually allows the symptoms to disappear promptly.

Figure A Figure B Figure C

Figure D Figure E Figure F

Use in specific populations

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Advate. It is not known whether Advate can cause fetal harm when administered to a pregnant woman, or whether it can affect reproductive capacity. Advate should be given to a pregnant woman only if clearly needed.

Labor and Delivery

There are no adequate and well-controlled human studies that have investigated the effects of Advate during labor and delivery. Advate should be used only if clinically needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Advate is administered to a nursing woman. Advate should be given to nursing mothers only if clinically needed.

Pediatric Use

In comparison to adults, children present with higher Factor VIII clearance values and thus lower half-life and recovery of Factor VIII. This may be explained by differences in body composition and should be taken into account when dosing or following Factor VIII levels in the pediatric population. Larger or more frequent doses should be considered to account for the observed differences in adjusted recovery and terminal half-life Dose adjustment may be needed. [see Pharmacokinetics (12.3)].

Geriatric Use

Clinical studies of Advate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects. Dose selection for a geriatric patient should be individualized.

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