International Approvals: Exubera, Kiovig, Wellbutrin XL

Yael Waknine

January 30, 2006

Jan. 30, 2006 — The European Commission has approved an inhalable formulation of recombinant human insulin for the treatment of adults with diabetes mellitus, and 10% intravenous immune globulin [human] for replacement therapy in primary immunodeficiency and autoimmune disorders. Canada's Therapeutic Products Directorate has approved bupropion HCl extended-release tablets for the treatment of major depressive disorder.


Inhalable Insulin (Exubera) for Type 1/2 Diabetes in Adults in EU

On January 26, the European Commission approved an inhalable formulation of recombinant human insulin (Exubera, made by Pfizer, Inc) for the treatment of adult patients with type 1 and type 2 diabetes mellitus for the control of hyperglycemia.

The inhalable dry powder formulation of insulin is available in 1- and 3-mg unit dose blisters. They are intended to be inhaled into the lungs 10 minutes prior to meals using a lightweight hand-held device approximately the size of an eyeglass case.

Although inhaled insulin has a duration of activity comparable to that of subcutaneously administered human insulin, its onset of action is similar to that of rapid-acting insulin analogs. In studies, peak insulin levels were achieved more rapidly with inhaled insulin compared with regular insulin (49 min [range, 30 - 90 min] vs 105 min [range, 60 - 240 min]).

In patients with type 1 diabetes, inhaled insulin should be used in regimens that include longer-acting insulins. In those with type 2 diabetes, it can be used as monotherapy or in combination with oral agents or longer-acting insulins.

The approval was based on clinical studies of more than 2500 patients (average treatment duration, 20 months), showing that inhaled insulin was similarly effective to injectable insulin for achieving glycemic control in adults with type 1 and type 2 diabetes, and for improved glycemic control in those with type 2 diabetes not adequately controlled with standard oral therapies.

Also, patients using the inhaled formulation reported greater overall treatment satisfaction and acceptance compared with insulin injections or oral therapies.

Adverse events were generally mild to moderate, and discontinuation rates were low. Hypoglycemia, cough, dyspnea, sore throat, and dry mouth were most commonly reported.

Use of inhaled insulin is contraindicated in patients with poorly controlled or unstable lung disease due to wide variations in lung function that could affect the drug's absorption and increase the risk for hyper- or hypoglycemia.

Inhaled insulin use is also contraindicated in patients who smoke or have ceased smoking within the last 6 months; treatment should be discontinued in those who start or resume smoking.

Lung function should be assessed via spirometry prior to initiating inhaled insulin therapy, checked again at 6 months, and annually thereafter. A small and potentially asymptomatic decrease in lung function may occur during the first few months of treatment.

Some patients have reported a mild cough within seconds to minutes of product inhalation; such episodes occurred less frequently as treatment continued.

Because consecutive inhalation of three 1-mg blisters causes a significantly higher insulin exposure than one 3-mg dose blister, these 2 regimens are not interchangeable.

The inhaled powder form of recombinant human insulin was approved by the US Food and Drug Administration on January 27.


10% IVIG (Kiovig) for Primary Immunodeficiency and Autoimmune Disorders in EU

On January 25, the European Commission approved 10% intravenous immune globulin [human] (IVIG; Kiovig, made by Baxter Healthcare SA) for use in the 25 states of the European Union, Norway, and Iceland.

The IVIG product is indicated for replacement therapy in primary immunodeficiency disorders, myeloma, or chronic lymphocytic leukemia with severe secondary hypogammaglobulinemia and recurrent infections, and children with congenital AIDS and recurrent infections.

It is also indicated for the treatment of Kawasaki syndrome, allogenic bone marrow transplantation, Guillain Barré syndrome, and idiopathic thrombocytopenic purpura in children and adults at high risk for bleeding or prior to surgery to correct platelet count.

The approval was based on data from a phase 3, multicenter study showing that no validated serious acute bacterial infections occurred in 61 patients treated with 300 to 600 mg per day of the solution every 21 to 28 days for a year.

The ready-to-use, sterile preparation eliminates the need for reconstitution, and its increased concentration compared with previously approved formulations (10% vs 5%) reduces the time required for infusion.

According to a company news release, it is the first and only 10% IVIG solution to offer the following combination of features: no added sugars, sodium, or preservatives; latex-free packaging; and an option for room-temperature storage for up to 9 months.

The IVIG product (marketed as Gammagard Liquid 10% by Baxter Healthcare Corporation) was previously approved in April 2005 by the US Food and Drug Administration for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. It is currently under consideration for approval by Canada's Therapeutic Products Directorate.


Extended-Release Bupropion Tablets (Wellbutrin XL) for Depression in Canada

On January 17, Canada's Therapeutic Products Directorate approved bupropion HCl 150- and 300-mg extended-release tablets (Wellbutrin XL, made by Biovail Corporation) for first-line use in the treatment of major depressive disorder in adults.

The approval was based on data showing that that the extended-release tablets demonstrated similar bioavailability to the immediate-release and sustained-release formulations under steady-state conditions (100 mg given 3 times daily and 150 mg given twice daily, respectively).

Extended-release bupropion tablets (marketed by GlaxoSmithKline) were approved by the US Food and Drug Administration in August 2003.

Reviewed by Gary D. Vogin, MD

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