Increased risk of marked hepatic enzyme elevations in patients taking SOMAVERT (pegvisomant) in combination with a somatostatin analogue - For Health Professionals

Starting date:

June 2, 2008

Posting date:

June 10, 2008

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Biologic/vaccine

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-170001890

This is duplicated text of a letter from Pfizer Canada Inc.

Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on Somavert (pegvisomant)

2008-06-02

Subject: Increased risk of marked hepatic enzyme elevations in patients taking Somavert^® (pegvisomant) in combination with a somatostatin analogue

Dear Health Care Professional,

Pfizer, in consultation with Health Canada, wishes to inform you of an increased risk of marked hepatic enzyme elevations in patients taking Somavert (pegvisomant) in combination with a somatostatin analogue (octreotide acetate).

Somavert, a growth hormone receptor antagonist, is indicated for the treatment of acromegaly in patients who have had an inadequate response to surgery, and/or radiation therapy, and other medical therapies, or for whom these therapies are not appropriate.

• Marked hepatic enzyme elevations (greater than 10 times upper limit of normal [ULN]) were reported in 3 out of 26 (approximately 10%) patients treated with the combination of Somavert and octreotide acetate in a post-marketing study.
• Data available from the literature^{Footnote 1}, indicate that 2 out of 32 patients (approximately 6%) treated with Somavert in combination with a somatostatin analogue have reported hepatic transaminases elevations greater than 10 times ULN.
• The combined use of Somavert and somatostatin analogues is not approved for the treatment of acromegaly as the safety and efficacy of this combination have not been established.

In a global post-marketing combination study with a somatostatin analogue, one out of 25 patients in the pegvisomant group and 1 out of 27 in the octreotide acetate group had transaminases greater than three or more times the upper limit of normal (ULN). Three patients out of 26 treated with the combination were found to have serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ranging from 13 to 45 times the ULN within 3 months of starting this treatment. Two of these patients received supratherapeutic doses of octreotide acetate (30 mg every 2 weeks) combined with a normal dose of Somavert (10 mg daily). All three patients completely recovered after discontinuation of treatment.

Neggers et al.^{Footnote 1} reported that elevated liver enzyme tests were observed in 11 out of 32 patients receiving pegvisomant in combination with a somatostatin analogue, at normal doses. Marked hepatic transaminases elevations greater than 10 times the ULN were reported in 2 of these patients, at least one of which is known to have been on octreotide acetate.

During pre-marketing clinical studies, marked elevations of hepatic enzymes greater than 10 times the ULN were reported in 0.8% of patients treated with Somavert.^{Footnote 2}

For all patients using Somavert, baseline serum ALT, AST, serum total bilirubin (TBIL), and alkaline phosphatase (ALP) levels should be obtained prior to initiating therapy with Somavert and monitored routinely during the course of treatment.

If a patient develops liver test (LT) elevations, or any other signs or symptoms of liver dysfunction while receiving Somavert the following patient management is recommended:

The Canadian Product Monograph will be revised to include this new information.

As part of Pfizer post-marketing safety activities, reports of abnormal hepatic function will continue to be closely monitored.

Healthcare professionals and patients who have additional questions may contact Pfizer Canada's medical information line at 1-800-463-6001.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious hepatic dysfunction or other serious or unexpected adverse reactions in patients receiving Somavert should be reported to Pfizer Canada Inc. or Health Canada at the following addresses:

Pfizer Canada Inc.

17300 Trans-Canada Highway

Kirkland, QC H9J 2M5

1-800-463-6001

Any suspected adverse reaction can also be reported to:

Canada Vigilance Program

Marketed Health Products Directorate

Health Canada

Address Locator: 0701C

Ottawa, Ontario, K1A 0K9

Tel: 613-957-0337

Fax: 613-957-0335

To report an Adverse Reaction, consumers and health professionals may call toll free:

Tel: 866-234-2345

Fax: 866-678-6789

CanadaVigilance@hc-sc.gc.ca

The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

For other inquiries related to this communication, please contact Health Canada at:

Marketed Health Products Directorate (MHPD)

E-mail: mhpd_dpsc@hc-sc.gc.ca

Tel: 613-954-6522

Fax: 613-952-7738

Sincerely,

original signed by

Bernard Prigent, MD, MBA

Vice-President and Medical Director

Pfizer Canada Inc.