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WinRho SDF (Rho(D) Immune Globulin Intravenous (Human)) Dear Healthcare Professional Letter Jan 2000

FDA posts safety alerts, public health advisories, press releases and other notices from companies as a service to health professionals, consumers and other interested parties. Although FDA approves medical products, FDA does not endorse either the product or the company.


This is the retyped text of a letter from Cangene Corporation and Nabi. Contact the company for a copy of any referenced enclosures.


Important Prescribing Information

January 3, 2000

Dear Healthcare Professional:

Cangene Corporation and Nabi® are committed to providing updated information to healthcare professionals to enable informed prescribing and treatment decisions regarding the use of our product WinRho SDF™ (Rho (D) Immune Globulin Intravenous (Human)). Based on a recent assessment of adverse events following administration of WinRho* to immune thrombocytopenic purpura (ITP) patients positive for Rho(D) antigen (D-positive), we have revised the package insert to state that "Rho(D) positive ITP patients treated with WinRho SDF should be monitored for signs and/or symptoms of intravascular hemolysis (IVH), clinically compromising anemia, and renal insufficiency."

Between April 1996 and April 1999, 15 cases that involved the acute onset of IVH following treatment of D-positive ITP patients with WinRho* were reported to the Food and Drug Administration (FDA). An additional 26 cases of possible IVH in ITP patients treated with WinRho were reported to FDA between May and October 1999 and are being further evaluated.

The 15 cases included four patients who died, one of whom died from complications secondary to IVH-induced exacerbation of anemia. Although the primary cause of death in the other three patients was related to underlying disease, the extent to which IVH-related clinical complications exacerbated their conditions and contributed to their deaths is unknown. Other clinical complications in the 15 patients included onset or exacerbation of anemia in seven patients (six of whom received packed red blood cells) and acute onset or exacerbation of renal insufficiency in eight patients (two of whom underwent dialysis). Six patients experienced more than one IVH-related complication.

An estimated incidence rate of 0.7 % for IVH following administration of WinRho for treatment of ITP was obtained from unpublished data from WinRho clinical trials1. However, this rate may underestimate the frequency of IVH because not all patients were monitored for IVH, which was observed only coincidentally.

The current WinRho SDF™ package insert references the occurrence of IVH under the Adverse Reactions/Treatment of ITP section, therefore, other sections of the labeling for the product will be modified to include all of the above information. This information can be found in the attached addendum.

Healthcare professionals should report serious adverse events possibly associated with the use of WinRho to Nabi at 1-800-327-7106. Alternatively, this information may be reported to FDA's MedWatch reporting system by phone (1-800-FDA-1088), facsimile (1-800-FDA-0178), the MedWatch website at www.fda.gov/medwatch, or mailed to MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20852-9787, using Form 3500, which is available from any of the above FDA listings.

If you have any additional questions regarding this information, please contact us directly.

Sincerely,

CANGENE CORPORATION
Andrew Storey
Vice President, Quality Assurance, Clinical and Regulatory Affairs

* WinRho includes all forms of product manufactured since licensure in 1995 [WinRho, WinRho SD, WinRho SDF]

1. Data available upon request.

 


Please refer to enclosed full prescribing information.
SUMMARY OF LABELING CHANGES

Precautions

Treatment of ITP

Following administration of WinRho SDF™ , Rho(D) positive ITP patients should be monitored for signs and/or symptoms of IVH, clinically compromising anemia, and renal insufficiency.

If patients are to be transfused, Rho(D) negative packed red blood cells [PRBCs] should be used so as not to exacerbate ongoing IVH. Platelet products may contain up to 5.0 mL of red blood cells [RBCs]; thus caution should likewise be exercised if platelets from Rho((D) positive donors are transfused.

Laboratory Tests

Treatment of ITP

Passively acquired anti-A, anti-B, anti-C, and anti-E blood group antibodies may be detectable in direct and indirect antiglobulin (Coombs) tests obtained following WinRho administration. Interpretation of direct and indirect antiglobulin tests must be made in the context of the patient's underlying clinical condition and supporting laboratory data.

Adverse Reactions

Treatment of ITP

In clinical trials of subjects (n=161) with childhood acute ITP, adults and children with chronic ITP, and adults and children with ITP secondary to HIV, 60/848 (7%) of infusions were associated with at least one adverse event that was considered to be related to the study medication. The most common adverse events were headache (19 infusions; 2%), chills (14 infusions; <2%), and fever (nine infusions; 1%). All are expected adverse events associated with infusions of immunoglobulins.

WinRho SDF™, Rho(D) Immune Globulin Intravenous (Human), is administered to Rho(D) positive patients with ITP. Therefore, side effects related to the destruction of Rho(D) positive red blood cells, most notably a decreased hemoglobin, can be expected. In four clinical trials of patients treated with the recommended initial intravenous dose of 50 µg/kg (250 IU/kg), the mean maximum decrease in hemoglobin was 1.70 g/dL (range +0.40 to -6.1 g/dL). At a reduced dose, ranging from 25 to 40 µg/kg (125 to 200 IU/kg), the mean maximum decrease in hemoglobin was 0.81 g/dL (range +0.65 to -1.9 g/dL). Only 5/137 (3.7%) of patients had a maximum decrease in hemoglobin greater than 4 g/dL (range 4.2 to 6.1 g/dL).

In most cases, the RBC destruction is believed to occur in the spleen. However, signs and symptoms consistent with IVH, including back pain, shaking chills, and/or hemoglobinuria, have been reported, occurring within 4 hours of WinRho administration.

IVH-related complications that have been reported include death (four cases reported between April 1996 and April 1999), onset or exacerbation of anemia, and acute onset or exacerbation of renal insufficiency. One patient died from complications secondary to IVH-induced exacerbation of anemia after administration of WinRho for treatment of ITP. Although the primary cause of death in the other three ITP patients treated with WinRho was related to underlying disease, the extent to which IVH-related clinical complications exacerbated their conditions and contributed to their deaths is unknown.

The mean maximum decrease in hemoglobin in patients who were not transfused with PRBCs was 3.5 g/dL (range: 0.0-7.6 g/dL). Transfusions for treatment-associated anemia were administered within hours to days of the onset of IVH and consisted of between 1-6 units of PRBCs. Acute renal insufficiency was noted within 2 to 48 hours of the onset of IVH. The mean maximum increase in serum creatinine in patients who did not undergo dialysis was 3.5 mg/dL (range: 0.8-10.3 mg/dL) and occurred within 2-9 days. The renal insufficiency in all surviving patients resolved with medical management, including dialysis, within 4-23 days.

The etiology of IVH following WinRho administration is unknown. No known risk factors associated with this adverse event have yet been identified from among those examined, which included age, gender, pre-treatment renal function, pre-treatment hemoglobin, concomitantly administered PRBCs, or WinRho dose.