Advate Side Effects
Generic Name: antihemophilic factor,antihemophilic factor (human),antihemophilic factor (recombinant)
Please note - some side effects for Advate may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects of Advate - for the Consumer
Advate
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Advate:
Seek medical attention right away if any of these SEVERE side effects occur when using Advate:Cough; diarrhea; headache; joint pain; sore throat; stuffy or runny nose; vomiting.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest or throat; swelling of the mouth, face, lips, or tongue; unusual hoarseness); burning numbness, or tingling; chest pain; dizziness; fainting; fever or chills; hot flashes; light-headedness; nausea; pain, swelling, or redness at the injection site; severe headache; shortness of breath; swelling of the legs; unusual bruising.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
TopAdvate Side Effects - for the Professional
Advate
The most serious adverse drug reactions (ADRs) seen with Advate are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments of Factor VIII..
The most common ADRs observed in clinical trials (frequency > 2% of subjects) were: Factor VIII inhibitor formation (observed predominantly in PUPs) and headache.(6.1)
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 patents (PTPs) and one ongoing study in 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 exposure to Advate per subject was 128.0 (range: 1 to 598) days.
There were 2,507 adverse events (AEs) reported in 215 subjects. None of the subjects withdrew from the studies due to adverse events. There were no deaths. Nineteen treated subjects reported no AEs during their participation. The most common AEs (product-related and unrelated, according to the investigator's opinion) occurring in at least 5% if subjects who received at least 1 Advate study infusion as shown in Table 3.
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MedDRA† System Organ Class |
MedDRA Preferred Term | Number of Events | Number of Subjects | Percent‡ of Subjects |
| Ear and labyrinth disorders | Ear pain | 17 | 14 | 6.0 |
| Gastrointestinal disorders | Constipation | 16 | 12 | 5.1 |
| Diarrhoea | 48 | 34 | 14.5 | |
| Nausea | 25 | 19 | 8.1 | |
| Vomiting | 53 | 38 | 16.2 | |
| General disorders and administration site conditions | Influenza like illness | 17 | 13 | 5.6 |
| Pain | 21 | 18 | 7.7 | |
| Pyrexia | 173 | 76 | 32.5 | |
| Infections and infestations | Ear infections | 40 | 25 | 10.7 |
| Influenza | 22 | 18 | 7.7 | |
| Nasopharyngitis | 121 | 62 | 26.5 | |
| Otitis media | 12 | 12 | 5.1 | |
| Sinusitis | 21 | 14 | 6.0 | |
| Upper respiratory tract infection | 49 | 31 | 13.2 | |
| Injury, poisoning and procedural complications | Accident | 41 | 20 | 8.5 |
| Fall | 22 | 17 | 7.3 | |
| Joint sprain | 16 | 14 | 6.0 | |
| Limb injury | 141 | 44 | 18.8 | |
| Procedural pain | 16 | 12 | 5.1 | |
| Musculoskeletal and connective tissue disorders | Arthralgia | 79 | 40 | 17.1 |
| Joint swelling | 15 | 13 | 5.6 | |
| Pain in extremity | 22 | 15 | 6.4 | |
| Nervous system disorders | Headache | 205 | 64 | 27.4 |
| Respiratory, thoracic and mediastinal disorders | Cough | 150 | 68 | 29.1 |
| Nasal congestion | 64 | 33 | 14.1 | |
| Pharyngolaryngeal pain | 50 | 32 | 13.7 | |
| Rhinorrhoea | 40 | 25 | 10.7 | |
| Skin and subcutaneous tissue disorders | Rash | 23 | 19 | 8.1 |
The majority of the events in Table 3 appear to have been related to trauma, intercurrent mild respiratory or gastrointestinal disease or well-described complications of hemophilia.
Fifty-six ADRs were reported in 27 subjects. Nearly all (53/56) were isolated events or occurred once in one subject with numerous subsequent infusions without reoccurrence. The most common ADRs with a frequency greater than or equal to 2% are shown in Table 4. Of all ADRs, none were reported in neonates, 16 were reported in infants, 7 were reported in children, 8 were reported in adolescents, and 25 were reported in adults.
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MedDRA System Organ Class |
MedDRA Preferred Term | Number of Patients |
ADR Rate (% Patients)† |
| Investigations | Anti-Factor VIII antibody positive | 5‡ | 2.14% |
| Nervous System Disorders | Headache | 5 | 2.14% |
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 of 0.03 and 2.91% for the risk of any Factor VIII inhibitor development). 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. 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 was also evaluated by measuring the development of antibodies to heterologous proteins. 182 treated subjects were assessed for anti-chinese hamster ovary 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 muIgGl protein antibodies. Of these 10 showed an upward trend in anti-mu IgG 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 5 represents the most frequently reported post-marketing adverse reactions as MedDRA Preferred Terms.
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| Organ System [MedDRA Primary SOC] | Preferred Term |
| Immune System Disorders: | Anaphylactic reaction* Hypersensitivity* |
| Blood And Lymphatic System Disorders: | Factor VIII inhibition |
| General disorders and administration site conditions |
Injection site reaction Chills Fatigue Malaise |
Side Effects by Body System - for Healthcare Professionals
Nervous system
Nervous system side effects have included headache, dizziness, somnolence, and asthenia.
Respiratory
Respiratory side effects have included dyspnea and rhinitis.
Musculoskeletal
Musculoskeletal side effects have included arthralgia.
Local
Local side effects have included injection site pain.
General
General side effects have included pyrexia and chills.
Gastrointestinal
Gastrointestinal side effects have included nausea, diarrhea, and vomiting.
Dermatologic
Dermatologic side effects have include pruritus, rash, and urticaria.
Cardiovascular
Cardiovascular side effects have included hemorrhage, hypotension, and vasodilatation.
TopMore Advate resources
- Advate MedFacts Consumer Leaflet (Wolters Kluwer)
- Advate Advanced Consumer (Micromedex) - Includes Dosage Information
- Advate Prescribing Information (FDA)
- Advate Consumer Overview
- Antihemophilic Factor Professional Patient Advice (Wolters Kluwer)
- Antihemophilic Factor (Human) Monograph (AHFS DI)
- Antihemophilic Factor (Recombinant) Monograph (AHFS DI)
- Helixate FS Prescribing Information (FDA)
- Kogenate Consumer Overview
- Kogenate FS MedFacts Consumer Leaflet (Wolters Kluwer)
- Kogenate FS Prescribing Information (FDA)
- Monoclate-P Prescribing Information (FDA)
- Recombinate Prescribing Information (FDA)
- Xyntha Prescribing Information (FDA)
- Xyntha MedFacts Consumer Leaflet (Wolters Kluwer)
- Xyntha Consumer Overview
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