Alphanate

Serious adverse drug reactions (ADRs) observed in patients receiving ALPHANATE include anaphylaxis/hypersensitivity reactions. Thromboembolic events also have been observed in patients receiving ALPHANATE for VWD [see WARNINGS AND PRECAUTIONS].

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse drug reaction (ADR) rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice.

In a prospective clinical study with ALPHANATE, 23 subjects were exposed to 1217 infusions (median=42, range 2-160). The total number of exposure days was 1133, and the total number of months on study across all subjects was 234 (19.5 subject years). No ADRs or inhibitors to FVIII were reported during the study.

In the prospective clinical study of ALPHANATE [using both ALPHANATE Solvent Detergent (A-SD, a previous generation product) and ALPHANATE Solvent Detergent/Heat Treated (A-SD/HT, the current generation product)] in subjects with von Willebrand Disease, ADRs occurred in 5 of 36 subjects (13.9%) treated with ALPHANATE.

Sixty-one total ADRs were reported in 204 infusions. The majority of ADRs were rated as mild (55 of 61 [90.2%]). Six ADRs (9.8%) were rated as moderate. No reactions rated as serious were reported. The adverse drug reaction grading scale is defined as follows:

• Mild: the event was noted but the administration of the compound was not interrupted; the event resolved spontaneously or no treatment was required beyond administration of nonprescription analgesics.
• Moderate: the administration of the compound was not necessarily interrupted; the event required momentary treatment with prescription drugs and produced no sequelae.

Overall, the proportion of infusions associated with ADRs was 14 of 204 infusions (6.9%). The most common ADRs reported ( > 1% of infusions) were pruritus, headache, backpain, paresthesia, respiratory distress, facial edema, pain, rash, and chills. One incident of pulmonary embolism was reported that was considered to have a possible relationship to the product. This subject received a dose of 60 IU VWF:RCo/kg body weight and the FVIII:C level achieved was 290%.

In the retrospective study conducted to determine the efficacy and safety of ALPHANATE (A-SD/ HT) in a surgical or invasive procedure setting as perioperative prophylaxis against excessive bleeding, [see Clinical Studies], 3 out of 39 subjects (7.7%) experienced 6 adverse drug reactions. Four were considered mild and 2 were considered moderate. No subject discontinued their treatment due to an adverse drug reaction. The adverse drug reactions were pruritus, paresthesia (2 events) and hemorrhage (all considered mild), and one event each of moderate hematocrit decrease and orthostatic hypotension.

One adverse drug reaction (pain) related to the treatment with heat-treated ALPHANATE (A-SD/ HT) was reported in the four pediatric subjects with von Willebrand Disease during the course of the prospective study and in none of the five pediatric subjects in the retrospective clinical study.

Post-Marketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The most common post-marketing ADRs reported include allergic/hypersensitivity reactions, nausea, fever, joint pain, fatigue, and infusion site pain.

In the U.S.

• Alphanate
• Humate-P
• Wilate

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antihemophilic Agent

Antihemophilic factor VIII and von Willebrand factor injection is a combination product that is used to treat serious bleeding episodes in patients with a bleeding problem called von Willebrand disease (VWD). The bleeding episode may be related to an injury (trauma) or a surgical procedure. This medicine may also be used to stop bleeding in patients with hemophilia A.

Antihemophilic factor VIII and von Willebrand factor are normally produced in the body. They help clot the blood when an injury occurs. Patients with von Willebrand disease or hemophilia A do not make enough of these substances to prevent bleeding, so this product is given to increase the levels of these substances in the blood.

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

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 VIII and von Willebrand factor injection in children 5 to 16 years of age.

Geriatric

Adequate and well-controlled studies have not been done on the relationship of age to the effects of antihemophilic factor VIII and von Willebrand factor injection in geriatric patients.

Pregnancy

Breast Feeding

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

• Blood clots, history of or
• Deep vein thrombosis (blood clot in leg), history of or
• Pulmonary embolism (blood clot in lung), history of or
• Stroke, history of—Use with caution. May make these conditions worse.

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

This medicine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have a cough, difficulty with swallowing, dizziness, a fast heartbeat, wheezing, shortness of breath, trouble breathing, chest tightness, swelling in your face, hands, tongue, or throat, a fever, chills, a runny nose or sneezing, itching or hives, or lightheadedness or faintness after you get the injection.

This medicine may increase your chance of having blood clots. Tell your doctor right away if you have a sudden or severe headache, problems with vision or speech, chest pain, shortness of breath, or numbness or weakness with this medicine.

This medicine is made from donated human blood. Some human blood products have transmitted certain viruses to people who have received them. The risk of getting a virus from medicines made from human blood has been greatly reduced in recent years. This is the result of required testing of human donors for certain viruses, and testing during the making of these medicines. Although the risk is low, talk with your doctor if you have concerns.

• If you have an allergy to Alphanate (antihemophilic factor/VWF complex (human)) or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Alphanate with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use Alphanate 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.
• Your doctor may 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.
• This medicine needs to be mixed before use. Follow how to mix as you were told by the doctor.
• Do not shake.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• 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.
• Use within 3 hours of making.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you are not sure what to do if you miss a dose, call your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of certain infections (parvovirus B19, hepatitis A) like fever or chills, feeling very sleepy, runny nose, rash, joint pain, tiredness, poor appetite, upset stomach or throwing up, belly pain, or yellow skin or eyes.
• Flushing.
• Very bad dizziness or passing out.
• Very bad headache.
• A burning, numbness, or tingling feeling that is not normal.
• Stinging.
• Swelling.
• Very upset stomach or throwing up.
• Feeling very tired or weak.
• Restlessness.
• Dark urine or yellow skin or eyes.
• Chest pain or pressure or a fast heartbeat.
• Shortness of breath.
• Coughing up blood.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Change in color of mouth to blue.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.

Safety has not been established during pregnancy; use only if clearly needed. AU TGA pregnancy category: Not formally assigned to a pregnancy category. US FDA pregnancy category: C

There are no controlled data in human pregnancy. Delivery confers an increased risk of hemorrhagic events in patients with von Willebrand disease. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

AU and UK: Safety has not been established; use only if clearly needed. US: Caution is recommended. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in the nursing infant are unknown.