Drug Safety
The Food and Drug Administration (FDA) performed a review of bisphosphonates, prompted by growing evidence over how long patients should continue using these agents.1 Concerns include osteonecrosis of the jaw, atypical femur fractures, and esophageal cancer in women that used this class of agents for three or more years. Three long-term trials were evaluated, looking at the meaningful endpoint of vertebral fracture rate, rather than any other endpoint previously identified as being important. When fracture data was pooled across trials in patients treated continuously for at least six years, fracture rates ranged from 9.3% to 10.6% for bisphosphonate therapy, whereas the fracture rate for patients switched to placebo was 8% to 8.8%. This raises the question of whether continuing bisphosphonates provides any additional fracture prevention benefit. In addition, more data are needed to determine whether markers of bone mineral density or bone turnover reliably help decisions related to continuing or interrupting bisphosphonate treatment. No studies have yet determined how long bisphosphonate benefits last. Although some patients may safely continue to take the drug, some may benefit from discontinuation. New treatment algorithms are needed, in light of available safety information.
Drug Approvals
After a long wait, clopidogrel (generic Plavix) has been FDA approved as a generic.2 Two dosage forms were approved—75 mg and 300 mg. Clopidogrel is approved for secondary stroke and myocardial infarction prophylaxis and for patients with peripheral artery disease. It became available from at least eight manufacturers in mid-May.
Hydromorphone 8 mg tablets (generic Dilaudid) are now available for treatment of pain.3
The first generic morphine sulfate oral solution available in 100 milligrams per 5 mL (20 milligrams per 1 mL) was recently FDA approved for relieving moderate to severe acute and chronic pain in opioid-tolerant patients.4 This form had been available but had not been FDA approved. It is now approved and meets U.S. safety requirements for approved drugs.
Phentermine HCl orally disintegrating tablets (Suprenza) have been FDA approved as a short-term adjunct in the management of exogenous obesity.5 Phentermine, a sympathomimetic amine anorectic, is FDA approved for treating obesity in patients with an initial body mass index of ≥30kg/m2 or ≥27kg/m2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia).
A supplemental New Drug Application (sNDA) has been submitted to the FDA seeking approval for the use of oral rivaroxaban (Xarelto) to treat deep vein thrombosis (DVT) or pulmonary embolism and prevent recurrent venous thromboembolism.6 Rivaroxaban is an oral anticoagulant, a factor Xa inhibitor, currently approved for the prophylaxis of DVT in people undergoing knee- or hip-replacement surgery and for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. On May 23, an FDA advisory committee recommended against approving rivaroxaban for treating acute coronary syndromes, citing missing safety and outcomes data.7 At press time, the FDA was expected to render a decision by the end of June.
Pipeline
CB-5945 is an oral mu opioid receptor and delta opioid receptor antagonist, currently in phase II clinical trials to treat opioid-induced constipation in patients with abdominal symptoms on chronic opioid therapy for persistent noncancer-related pain.8 In two phase II clinical trials, the drug was dosed once and twice daily over four weeks, with opioid consumption, pain scores, and adverse events monitored. The most commonly reported adverse events were abdominal pain and upper respiratory tract infection. Gastrointestinal-related adverse events were mostly mild with a low incidence. Phase III trials are planned.