There is a large amount of interesting research underway for SLE, and we will see more clinical trial results as these novel agents work their way through the development pipeline.
New Approvals
Morphine sulfate high-concentration solution (100 mg per 5 mL) has been approved by the U.S. Food and Drug Administration (FDA) for the management of opioid-tolerant patients with moderate-to-severe acute and chronic pain, as well as for end-of-life care.10 Early in 2009, the FDA established an initiative to remove unapproved narcotic formulations from the market, products that were never approved by the FDA. Because of this, they were not subjected to safety, efficacy, bioavailability, or dose-ranging studies, as they are today. The FDA sent warning letters to nine pharmaceutical manufacturers, of which seven manufactured high-concentration morphine sulfate products. When the FDA realized there were no FDA-approved high-concentration morphine sulfate products on the market, they gave the manufacturers a reprieve from the ruling so as not to disrupt patient care. Since then, the FDA has worked with one manufacturer (Roxane) to bring this product to market. As part of this agent’s approval, the manufacturer established a safety profile to focus on the risks of misuse, abuse, and overuse. This product will likely be available with a Risk Evaluation and Mitigation Strategy (REMS).
NP-1 (topical amitriptyline/ketamine) has received orphan drug approval status from the FDA for the management of post-herpetic neuralgia (PHN).11 In phase II studies of patients with PHN, it had at least equivalent effectiveness compared to gabapentin.
Tocilizumab (Actemra) has been approved by the FDA to treat adults with moderate to severe active rheumatoid arthritis (RA) and who have not had an adequate response to one or more tumor necrosis inhibitor therapies.12 Tocilizumab is the first interleukin-6 receptor antagonist monoclonal antibody approved for the treatment of RA. Prior to approval, tocilizumab was studied in five late-stage studies in more than 4,000 patients, either given alone or in combination with methotrexate or other disease-modifying antirheumatic drugs. This agent is approved for the same use in the European Union (EU) under the brand name RoActemra.
Pipeline
- Denosumab (Prolia), currently in phase III clinical trials in the United States, has received a positive opinion from the authorization of marketing by the Committee for Medicinal Products for Human Use of the European Medicines Agency in the EU for the treatment of postmenopausal osteoporosis in women at risk for fractures, as well as for treating bone loss in men with prostate cancer at increased fracture risk.13,14
- Phase III clinical trials have been completed for insulin ultra-rapid acting, rDNA origin (Afrezza). As an inhaled insulin product, its pH-sensitive particles immediately dissolve when in contact with the lung surface, releasing insulin monomers that rapidly cross into the systemic circulation.15 It achieves peak insulin levels within 12 to 14 minutes of being administered, which mimics mealtime insulin observed in nondiabetics. The new drug application was filed, and it was originally expected to be reviewed by mid-January 2010, so the FDA is likely to act on it soon.
- Lidocaine topical patch 5%, a generic version of Lidoderm, had an abbreviated new drug application filed for it on January 21, 2010. Although this agent is FDA-approved for treating pain related to PHN, there are other off-label evidence-based uses for this agent.16 The first Lidoderm patent is set to expire in mid-March 2010.17
Safety
Diclofenac gel 1% (Voltaren gel), the topical nonsteroidal antiinflammatory agent used to relieve ostearthritis pain, has undergone a safety change to its label related to hepatic effects, including revised warnings and precautions about the potential for liver function test elevations while receiving treatment with this agent and all diclofenac- containing products.18 Postmarketing case reports have been identified related to drug-induced hepatotoxicity within the first month of treatment with topical diclofenac (these can occur any time during treatment). Through postmarketing surveillance, severe hepatic reactions have been reported, including fulminant hepatitis with and without jaundice, jaundice, liver necrosis, and liver failure. Some cases led to death or liver transplantation. It is recommended that patients receiving topical diclofenac be monitored with periodic transaminase measurements, particularly in patients receiving long-term therapy. A baseline measurement should be obtained before treatment followed by subsequent measurements (at unspecified intervals). Current data based on clinical trials and other cases suggest that transaminase levels be obtained within four to eight weeks after initiating diclofenac treatment, and subsequently thereafter.