International Approvals: Torisel, Rocephin, Sigmart

Yael Waknine

December 03, 2007

December 3, 2007 — The European Commission has approved temsirolimus injection for the first-line treatment of advanced renal cell carcinoma. Japan's Ministry of Health, Labor, and Welfare has approved once-daily administration of ceftriaxone injection in children, as well as nicorandil injection for the treatment of acute heart failure.

Temsirolimus Injection ( Torisel) for Advanced Kidney Cancer in EU

On November 26, the European Commission (EC) approved temsirolimus injection ( Torisel, Wyeth Pharmaceuticals, Inc) for the first-line treatment of advanced renal cell carcinoma in patients who have at least 3 of 6 prognostic risk factors.

Risk factors include having had less than 1 year elapse since initial diagnosis, Karnofsky performance status of 60 or 70, hemoglobin level less than the lower limit of normal, corrected calcium level higher than 10 mg/dL, lactate dehydrogenase level more than 1.5 times the upper limit of normal, and more than 1 metastatic organ site.

Temsirolimus is administered as a 25-mg dose infused during a 30- to 60-minute period once weekly; treatment should continue until disease progression or unacceptable toxicity occurs. Prophylactic diphenhydramine (25 – 50 mg) should be administered intravenously approximately 30 minutes before each treatment.

The approval was based on data from a phase 3 clinical trial in which 626 patients with advanced renal cell carcinoma were randomly assigned to receive temsirolimus, interferon-alpha, or both. Results showed that temsirolimus therapy increased median overall survival by 49% compared with interferon-alpha (10.9 vs 7.3 months; P = .0078; hazard ratio, 0.73; 95% confidence interval, 0.58 – 0.92).

Progression-free survival, a secondary endpoint, was likewise significantly improved (5.5 vs 3.1 months; P = .0001; hazard ratio, 0.66; 95% confidence interval, 0.53 – 0.81). Use of the drug combination did not significantly increase overall survival relative to interferon-alpha alone.

Adverse events most commonly reported (incidence ≥ 30%) in patients receiving temsirolimus therapy included asthenia (51%), rash (47%), mucositis (41%), nausea (37%), edema (35%), and anorexia (32%). The most common laboratory abnormalities were anemia (94%), hyperglycemia (89%), hyperlipemia (87%), hypertriglyceridemia (83%), elevated alkaline phosphatase levels (68%), elevated serum creatinine levels (57%), lymphopenia (53%), hypophosphatemia (49%), thrombocytopenia (40%), elevated aspartate aminotransferase levels (38%), and leukopenia (32%).

Regular monitoring of complete blood counts and chemistry panels is advised; interruption of treatment may be required for patients with severe bone marrow suppression. Increased glucose levels may necessitate uptitration of insulin and/or oral hypoglycemic therapy, and increases in serum triglycerides may require initiation or uptitration of lipid-lowering agents.

Temsirolimus previously was approved by the US Food and Drug Administration on May 30, 2007.

Ceftriaxone Injection ( Rocephin) for Once-Daily Use in Children in Japan

On November 13, Japan's Ministry of Health, Labor, and Welfare approved a new dosing regimen for ceftriaxone for injection ( Rocephin, Chugai Pharmaceutical Company, Ltd, under license from Roche), allowing its once-daily administration in pediatric patients.

Ceftriaxone injection is recommended in Japan as first-line therapy for infectious diseases such as community-acquired pneumonia, meningitis, biliary tract infection, and gonococcal infection, the company says in a news release.

The recent emergence of drug-resistant bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, has presented problems, resulting in many pediatric cases of acute otitis media and community-acquired pneumonia. According to the news release, use of ceftriaxone is expected to produce a therapeutic effect on these cases.

Recently, the US Food and Drug Administration (FDA) warned against concomitant use of ceftriaxone and calcium-containing solutions/products because of the risk for fatal reactions with calcium-ceftriaxone precipitates in the lungs and kidneys.

Although such cases have been reported in term and premature neonates, all age groups are at potential risk for the reaction. A minimum of 48 hours should elapse between the last dose of ceftriaxone and use of calcium-containing products or those reconstituted with calcium-containing diluents such as Ringer's or Hartmann's solution.

Ceftriaxone injection previously was approved by the FDA for once- or twice-daily use in children.

Nicorandil Injection ( Sigmart) for Acute Heart Failure in Japan

On October 23, Japan's Ministry of Health, Labor, and Welfare (MHLW) approved an expanded indication for nicorandil injection ( Sigmart, Chugai Pharmaceutical Company, Ltd), allowing its use for the treatment of acute heart failure, including acute decompensation of chronic heart failure.

"Acute heart failure, which 250 thousand people suffer from per year in Japan, is treated with oxygen inhalation, diuretics, and intravenous vasodilators and inotropic drugs," the company says in a news release.

Nicorandil combines nitrate-like action and adenosine triphosphate–sensitive potassium channel opening abilities to improve pre- and postload in a balanced manner, offering a new therapeutic option for patients requiring intravenous vasodilatory therapy.

Nicorandil previously was approved by the MHLW for the treatment of unstable angina pectoris. It has not been approved by the US Food and Drug Administration.


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