FDA Approvals: ACTOplus met XR, Azor, Vancomycin HCl Injection

Yael Waknine

May 21, 2009

May 21, 2009 — The US Food and Drug Administration (FDA) has approved pioglitazone HCl and metformin HCl extended-release tablets for the adjunctive treatment of type 2 diabetes mellitus, amlodipine and olmesartan medoxomil tablets for first-line use in the treatment of hypertension, and a 10-g vial size for vancomycin HCl injection.

Pioglitazone HCl/Metformin HCl Extended-Release Tablets (ACTOplus met XR) for Type 2 Diabetes

On May 12, the FDA approved pioglitazone HCl and metformin HCl extended-release tablets (ACTOplus met XR; Takeda Pharmaceutical Co, Ltd) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already receiving pioglitazone and metformin or who have inadequate glycemic control with either drug alone.

According to a company news release, it is the first and only prescription once-daily oral antidiabetic fixed-dose combination product available with the extended-release form of metformin.

The recommended starting dose for pioglitazone-metformin extended-release tablets is one 15-mg/1000-mg or 30-mg/1000-mg tablet administered once daily with the evening meal; this dose may be gradually uptitrated to a maximum of 45 mg/2000 mg depending on clinical response and tolerance. Patients initiating therapy or receiving dose increases should be monitored carefully for signs and symptoms of heart failure, including excessive and rapid weight gain, dyspnea, and/or edema. Use of the product in the setting of New York Heart Association class III or IV heart failure is contraindicated.

Patients receiving pioglitazone-metformin therapy should be informed that the extended-release tablets must be swallowed whole and not chewed, cut, or crushed, and that inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet.

Because metformin is substantially excreted by the kidneys and its accumulation has been linked to a risk for potentially fatal lactic acidosis, pioglitazone-metformin products should not be used in patients with kidney disease or renal impairment.

Similarly, treatment with pioglitazone-metformin should not be initiated in patients with clinical evidence of active liver disease or increased serum transaminase levels (alanine aminotransferase > 2.5 the upper limit of normal). Liver enzyme monitoring is recommended before initiation of therapy and periodically thereafter.

A pioglitazone and immediate-release metformin combination product (ACTOplus met) previously was approved by the FDA for the adjunctive treatment of type 2 diabetes mellitus.

Amlodipine and Olmesartan Medoxomil (Azor) Approved as First-Line Antihypertensive

On May 11, the FDA approved an expanded indication for amlodipine and olmesartan medoxomil tablets (Azor; Daiichi Sankyo, Inc), allowing use of the dihydropyridine calcium channel blocker plus angiotensin II receptor blocker combination product as first-line therapy in patients likely to require multiple antihypertensive agents to achieve their blood pressure goals.

"The approval of Azor as a first-line therapy gives doctors an important treatment option that may help the many patients who require multiple medications avoid several treatment steps to achieve their blood pressure goals," said Keith C. Ferdinand, MD, in a company news release. "Fixed-dose combinations like Azor provide patients with a more convenient option than separate monotherapies, which may help simplify the treatment regimen and decrease overall pill burden."

Dr. Ferdinand is chief science officer of the Association of Black Cardiologists and a clinical professor at the Emory School of Medicine in Atlanta, Georgia.

Approval of the product for first-line use was based on data from an 8-week, placebo-controlled, parallel-group factorial study that provided estimates of the probability of patients attaining blood pressure goals with amlodipine-olmesartan vs either component alone, based on baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling from all available data.

These figures are included in the prescribing monograph to provide an approximation of the likelihood of reaching a targeted blood pressure goal.

Amlodipine and olmesartan tablets previously were approved by the FDA for second-line use alone or with other agents in the treatment of hypertension.

Vancomycin Injection Now Available in 10-g Pharmacy Bulk Vials

On April 29, the FDA approved a 10-g pharmacy bulk vial of sterile vancomycin HCl injection (Hospira, Inc).

"This approval means Hospira now offers the most complete product portfolio of this important drug, which is an effective agent for fighting methicillin-resistant Staphylococcus aureus (MRSA)," the company said in a news release, noting that MRSA infections are often resistant to other antibiotics.

The glycopeptide antibiotic previously was approved in 500-mg, 750-mg, and 1-g dosages; and in 5-g pharmacy bulk packages.

Vancomycin is indicated for the treatment of serious, life-threatening infections by gram-positive bacteria that are unresponsive to other less toxic antibiotics.

To control the spread of vancomycin resistance, the Centers for Disease Control and Prevention advises that vancomycin therapy be restricted to the treatment of serious infections caused by susceptible organisms resistant to penicillins, pseudomembranous colitis refractory to metronidazole, infections caused by gram-positive microorganisms in patients with severe allergies to beta-lactam antimicrobials, antibacterial prophylaxis for endocarditis after certain procedures in penicillin-hypersensitive individuals at high risk, and as surgical prophylaxis for major procedures involving implantation of prostheses in institutions having a high rate of MRSA or methicillin-resistant S epidermidis.

Azor Prescribing Information

FDA New Drug Information