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:

Cough; diarrhea; headache; joint pain; sore throat; stuffy or runny nose; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Advate:

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.

Top

Advate 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.

 

Table 3. Adverse Events Reported by > 5% Treated of Study Subject*

* Includes data from 234, treated subjects from 5 completed studies in PTPs, and 1 ongoing study in PUPs as of 27 March 2006. † MedDRA version 8.1 was used. ‡ This percent is calculated relative to 234, the total number of treated subjects.
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.

Table 4. Summary of Most Common Adverse Drug Reactions (ADRs)* with a frequency ≥ 2%

* ADR = Adverse Drug Reaction = adverse events considered by the investigator to be at least possibly related to administration of the product. † 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. ‡ All 5 ADRs occurred in (PUPs) from an ongoing clinical study, and all were for the development of Factor VIII inhibitors with a titer ≥ 0.6 BU that were to be reported as a serious AE.
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.

Table 5. Post-Marketing Experience

* These reactions and have been manifested by dizziness, paresthesias, rash, flushing, face swelling, urticaria, and/or pruritus.
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

Top

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.

Top

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.