Advate

Advate Side Effects Center

What Is Advate?

Advate [antihemophilic factor (recombinant), plasma/albumin-free method] is a purified glycoprotein used to control and prevent bleeding episodes in adults and children with Hemophilia A, for perioperative management in adults and children with Hemophilia A, and for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with Hemophilia A. Advate is not indicated for the treatment of von Willebrand disease.

What Are Side Effects of Advate?

Common side effects of Advate include:

Dosage for Advate

The dosage and duration of treatment with Advate depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the patient's clinical condition.

What Drugs, Substances, or Supplements Interact with Advate?

Advate may interact with other drugs. Tell your doctor all medications and supplements you use.

Advate During Pregnancy or Breastfeeding

During pregnancy, Advate should be administered only if prescribed. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Advate [antihemophilic factor (recombinant), plasma/albumin-free method] Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Advate Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives, itching, rash, numbness, tingling; fever, dizziness, nausea; fast heartbeats, chest tightness, wheezing, difficult breathing; pale skin, cold sweat, feeling light-headed, fainting; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

increased bleeding episodes;
any bleeding that will not stop;
chest pain; or
a light-headed feeling, like you might pass out.

Common side effects may include:

nose bleeds;
nausea, vomiting, diarrhea;
headache, dizziness;
muscle or joint pain;
rash;
flushing (sudden warmth, redness, or tingly feeling);
fever, chills;
cough;
weakness; or
pain, swelling, itching, or redness where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Advate ([Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] for Intravenous Injection)

Advate Professional Information

SIDE EFFECTS

The serious adverse drug reactions (ADRs) seen with ADVATE are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments to Factor VIII.

The most common ADRs observed in clinical trials (frequency ≥ 10% of subjects) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, limb injury.

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction 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.

ADVATE has been evaluated in five completed studies in previously treated patients (PTPs) and one ongoing study in previously untreated patients (PUPs) with severe to moderately severe Hemophilia A (Factor VIII ≤ 2% of normal). A total of 234 subjects have been treated with ADVATE as of March 2006. Total exposure to ADVATE was 44,926 infusions. The median duration of participation per subject was 370.5 (range: 1 to 1,256) days and the median number of exposure days to ADVATE per subject was 128.0 (range: 1 to 598).³

The summary of adverse reactions (ADRs) with a frequency ≥ 5% (defined as adverse events occurring within 24 hours of infusion or any event causally related occurring within study period) is shown in Table 3.

No subject was withdrawn from a study due to an ADR. There were no deaths in any of the clinical studies.

Table 3: Summary of Adverse Reactions (ADRs)^a with a Frequency ≥ 5% in 234 Treated Subjects^b

MedDRA^c System Organ Class	MedDRA Preferred Term	Number of ADRs	Number of Subjects	Percent of Subjects
General disorders and administration site conditions	Pyrexia	78	50	21
Nervous system disorders	Headache	104	49	21
Respiratory, thoracic and mediastinal disorders	Cough	75	44	19
Infections and infestations	Nasopharyngitis	61	40	17
Gastrointestinal disorders	Vomiting	35	27	12
Musculoskeletal and connective tissue disorders	Arthralgia	44	27	12
Injury, poisoning and procedural complications	Limb injury	55	24	10
Infections and infestations	Upper respiratory tract infection	24	20	9
Respiratory, thoracic and mediastinal disorders	Pharyngolaryngeal pain	23	20	9
Respiratory, thoracic and mediastinal disorders	Nasal congestion	24	19	8
Gastrointestinal disorders	Diarrhea	24	18	8
Gastrointestinal disorders	Nausea	21	17	8
General disorders and administration site conditions	Pair	19	17	8
Skin and subcutaneous tissue disorders	Rash	16	13	6
Infections and infestations	Ear infection	16	12	5
Injury, poisoning and procedural complications	Procedural pain	16	12	5
Respiratory, thoracic and mediastinal disorders	Rhinorrhea	15	12	5
^a ADRs are defined as all Adverse Events that occurred (a) within 24 hours after being infused with investigational product or (b) all Adverse Events assessed related or possibly related to investigational product or (c) Adverse Events for which the investigator's or sponsor's opinion of causality was missing or indeterminate. ^b The ADVATE clinical program included 234 treated subjects from 5 completed studies in PTPs and 1 ongoing study in PUPs as of 27 March 2006. ^c MedDRA version 8.1 was used.

Immunogenicity

The development of Factor VIII inhibitors with the use of ADVATE was evaluated in clinical studies with pediatric PTPs ( < 6 years of age with > 50 Factor VIII exposures) and PTPs ( ≥ 10 years of age with > 150 Factor VIII exposures). Of 198 subjects who were treated for at least 10 exposure days or on study for a minimum of 120 days, 1 adult developed a low-titer inhibitor (2.0 [BU] in the Bethesda assay) after 26 exposure days. Eight weeks later, the inhibitor was no longer detectable, and in vivo recovery was normal at 1 and 3 hours after infusion of another marketed recombinant Factor VIII concentrate. This single event results in a Factor VIII inhibitor frequency in PTPs of 0.51% (95% CI 0.03 to 2.91% for the risk of any Factor VIII inhibitor development).3,4 No Factor VIII inhibitors were detected in the 53 treated pediatric PTPs.

In clinical studies that enrolled previously untreated subjects (defined as having had up to 3 exposures to a Factor VIII product at the time of enrollment), 5 (20%) of 25 subjects who received ADVATE developed inhibitors to Factor VIII.3 Four patients developed high titer ( > 5 BU) and one patient developed low-titer inhibitors. Inhibitors were detected at a median of 11 exposure days (range 7 to 13 exposure days) to investigational product.

Immunogenicity also was evaluated by measuring the development of antibodies to heterologous proteins. 182 treated subjects were assessed for anti-Chinese hamster ovary (CHO) cell protein antibodies. Of these patients, 3 showed an upward trend in antibody titer over time and 4 showed repeated but transient elevations of antibodies. 182 treated subjects were assessed for muIgG protein antibodies. Of these, 10 showed an upward trend in anti-muIgG antibody titer over time and 2 showed repeated but transient elevations of antibodies. Four subjects who demonstrated antibody elevations reported isolated events of urticaria, pruritus, rash, and slightly elevated eosinophil counts. All of these subjects had numerous repeat exposures to the study product without recurrence of the events and a causal relationship between the antibody findings and these clinical events has not been established. Of the 181 subjects who were treated and assessed for the presence of anti-human von Willebrand Factor (VWF) antibodies, none displayed laboratory evidence indicative of a positive serologic response.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of ADVATE. 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.

Among patients treated with ADVATE, cases of serious allergic/hypersensitivity reactions including anaphylaxis have been reported and Factor VIII inhibitor formation (observed predominantly in PUPs). Table 4 represents the most frequently reported post-marketing adverse reactions as MedDRA Preferred Terms.

Table 4: Post-Marketing Experience

Organ System [MedDRA Primary SOC]	Preferred Term
Immune system disorders	Anaphylactic reaction^aHypersensitivity^a
Blood and lymphatic system disorders	Factor VIII inhibition
General disorders and administration site conditions	Injection site reaction Chills Fatigue/Malaise Chest discomfort/pain Less-than-expected therapeutic effect
^a These reactions have been manifested by dizziness, paresthesias, rash, flushing, face swelling, urticaria, and/or pruritus.

Read the entire FDA prescribing information for Advate ([Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] for Intravenous Injection)

&Copy; Advate Patient Information is supplied by Cerner Multum, Inc. and Advate Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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