Indication: ADVATE is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for: Control and prevention of bleeding episodes. Perioperative management; Routine prophylaxis to prevent or reduce the frequency of bleeding episodes. ADVATE is not indicated for the treatment of von Willebrand disease.

ADVATE has an established safety profile in PTPs1

PTP clinical studies1

The safety of ADVATE was evaluated from 8 studies in 276 PTPs with moderately severe to severe hemophilia A. PTPs were defined as having ≥50 or ≥150 exposure days (EDs) to FVIII products, depending on the study. In this analysis, PTPs were defined as patients with ≥50 EDs. For PTP inhibitor incidence, all PTPs with ≥10 consecutive EDs (N=276) during the course of individual studies were included in the analysis. EDs were defined as calendar days on which rAHF-PFM was administered.

AHF=antihemophilic factor (recombinant), plasma/albumin-free method; PTP=previously treated patient.

Low risk of factor VIII inhibitor development in PTPs demonstrated in clinical studies1

8 clinical studies showed 0.36% incidence of factor VIII inhibitors in PTPs.

8 clinical studies showed 0.36% incidence of factor VIII inhibitors in 276 PTPs with moderately severe to severe hemophilia A (95% CI: 0.009%-2.002%)1

  • 1 PTP developed a nonpersistent, low-titer factor VIII inhibitor.1
  • There was 1 additional case of a possible low-titer factor VIII inhibitor, which was unconfirmed, unaccompanied by symptoms of inhibitor presence, and disappeared at the subject’s subsequent test.2

PTP=previously treated patient.

ADVATE has an established safety profile in PUPs and MTPs3,4

PUPs and MTPs clinical study design3,4

The safety of ADVATE was evaluated in a multicenter, open-label clinical study of 55 PUPs and MTPs <6 years of age with severe (factor VIII level <1%) or moderately severe (factor VIII level 1% - 2%) hemophilia A determined at baseline. PUPs and MTPs were defined as having had up to 3 exposures to a factor VIII product at time of enrollment. Patients were followed for 75 exposure days or 3 years, whichever occurred first. The primary safety endpoint was the percentage of patients who developed an inhibitor to factor VIII.

MTP=minimally treated patient, having had up to 3 exposures to a factor VIII product at time of enrollment in clinical study; PUP=previously untreated patient.

Selected Important Risk Information

Warnings & Precautions

Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

Please see additional detailed important risk information below.

The risk of inhibitor development was further evaluated in a study investigating immunogenicity in 55 PUPs and MTPs.3,4

The clinical study showed 29.1% incidence of factor VIII inhibitors in PUPs and MTPs.

The study showed 29.1% incidence of factor VIII inhibitors in PUPs and MTPs (16/55) (95% CI: 17.1%-41.1%)3,4

  • Factor VIII inhibitors were detected at a median of 13 EDs; min-max: 6-26 EDs3
  • 7 patients developed high-titer (>5 BU) factor VIII inhibitors, and 9 patients developed low-titer factor VIII inhibitors3

BU=Bethesda unit; ED=exposure days; MTP= minimally treated patient, having had up to 3 exposures to a factor VIII product at time of enrollment in clinical study; PUP=previously untreated patient.

Hypersensitivity reactions reported with ADVATE

Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with ADVATE. Symptoms include the following3:

  • Dizziness
  • Paresthesia
  • Rash
  • Flushing
  • Facial swelling
  • Urticaria
  • Dyspnea
  • Pruritus
  • Vomiting

Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment.

ADVATE adverse reactions observed in clinical trials

The most common adverse reactions observed in clinical trials, in >5% of subjects, included the following3:

  • Pyrexia
  • Headache
  • Cough
  • Nasopharyngitis
  • Arthralgia
  • Vomiting
  • Upper respiratory tract infection
  • Limb injury
  • Nasal congestion
  • Diarrhea
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  1. Shapiro AD, Schoenig-Diesing C, Silvati-Fidell L, Wong WY, Romanov V. Integrated analysis of safety data from 12 clinical interventional studies of plasma- and albumin-free recombinant factor VIII (rAHF-PFM) in haemophilia A. Haemophilia. 2015;21(6):791-798. doi:10.1111/hae.12724
  2. Valentino LA, Mamonov V, Hellmann A, et al. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012;10(3):359-367. Published correction appears in J Thromb Haemost. 2012;10(6):1204.
  3. Advate. Prescribing information. Baxalta US Inc; 2018.
  4. Auerswald G, Thompson AA, Recht M, et al. Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A. Thromb Haemost. 2012;107(6):1072-1082. doi:10.1160/TH11-09-0642