News

FDA Approves First IV Osteoporosis Therapy


 

Last month, the Food and Drug Administration approved an injectable formulation of ibandronate, the first intravenous treatment for osteoporosis to become available and the first bisphosphonate administered once every 3 months.

The approved dose is 3 mg, administered intravenously over 15–30 seconds, by a health care professional, once every 3 months. Ibandronate is the third such formulation approved by the FDA; the first, a daily 2.5-mg formulation approved in 2003, was never marketed because of the availability of more convenient weekly bisphosphonate formulations that were already available at that time. A monthly oral formulation of ibandronate (150 mg) was approved and marketed almost a year ago. Like the monthly formulation, the IV formulation will be marketed under the trade name Boniva, by Hoffmann-La Roche. It will be available “early this year,” according to a press release announcing the approval. At press time, the company had not provided information on its cost.

Bypassing the esophagus and stomach—eliminating the need to sit upright without drinking or eating for 30–60 minutes after taking an oral bisphosphonate that is required to reduce the risk of esophagitis and gastritis—is perhaps the most obvious advantage of the IV formulation, said Dr. Robert Recker, director of the Creighton University Osteoporosis Research Center, Omaha, Neb.

Injectable ibandronate can also be used for patients who cannot swallow well, and having the patient come to the office once every 3 months for an injection assures compliance and may be more convenient for patients, added Dr. Recker, who is also professor of medicine and chief of the division of endocrinology at the University. He is a consultant to Roche, and to manufacturers of other osteoporosis therapies, and has conducted clinical trials funded by all these companies.

Dr. Recker was among the investigators in the DIVA (the Dosing Intravenous Administration) study, a randomized, double-blind multinational “noninferiority” study of 1,358 women with postmenopausal osteoporosis. The study compared 2.5 mg of ibandronate daily with the injectable formulation once every 3 months; at 1 year, bone mineral density (BMD) of the lumbar spine had increased by a mean of 4.5% among those on the IV treatment vs. a mean of 3.5% among those on daily therapy, a highly statistically significant difference. Increases in the total hip, femoral neck and trochanter BMD were also greater among those on IV ibandronate.

Because the 2.5-mg daily formulation has already been shown to reduce the risk of new vertebral fractures over 3 years in studies that were the basis of that formulation's approval, antifracture efficacy data on IV ibandronate were not required for approval.

Overall safety and tolerability of IV ibandronate was similar to that associated with the daily oral dose in the DIVA study, with arthralgia, abdominal pain, and back pain among the most commonly reported side effects. Some patients experience a mild flu-like syndrome with the first injection, which, if necessary, is easily suppressed with aspirin, acetaminophen, or an NSAID, although some people do not need to take anything, Dr. Recker said.

Because IV bisphosphonates have been associated with renal toxicity, serum creatinine should be checked before each dose, and patients with severe renal impairment should not receive the drug, according to the product's label (package insert), approved by the FDA. No cases of acute renal failure were reported in controlled trials where IV Boniva was administered over 15–30 seconds. Like other bisphosphonates, ibandronate inhibits osteoclast-mediated bone resorption, reducing the elevated rate of bone turnover. The other two bisphosphonates approved for treating postmenopausal osteoporosis are alendronate (Fosamax) and risedronate (Actonel), which are administered weekly, and are also approved for prevention of osteoporosis.

To get the most benefits from bisphosphonates, Dr. Recker stressed taking a daily absorbable calcium supplement of more than 1,200 mg of calcium a day taken in divided doses with meals, and a vitamin D supplement. He recommends 1,000 mg of vitamin D3 every day, not vitamin D2, which is in most supplements.

Next Article: