Wednesday, December 1, 2010

Dec2010 – Pain Product Announcements & Warnings

AnnouncementsFeatured Items: denosumab (Xgeva) approval; duloxetine hcl (Cymbalta) approval for musculoskeletal pain; acetaminophen IV (Ofirmev) approval; propoxyphene-containing analgesics (Darvon, Darvocet) withdrawn. — Brand names are trademarks of their respective manufacturers. Compiled by Winnie Dawson, MA, RN, BSN.

Denosumab (Xgeva™) — FDA Approved For Cancer-Related Bone Pain
Amgen received a November 2010 U.S. Food and Drug Administration approval for Xgeva to reduce bone pain and other skeletal-related events in patients with bone metastases from solid tumors. The drug was given a 6-month priority review because it offered an advance in the treatment of metastatic bone pain and skeletal-related events (SREs). Xgeva is a human IgG2 monoclonal antibody that binds and inhibits RANKL, a protein that is essential for cells responsible for bone resorption. The drug, a reformulation of the osteoporosis drug Prolia, is administered every 4 weeks as a 120 mg subcutaneous injection.

Clinical trials compared Xgeva with Zometa — a bisphosphonate derivative — in more than 5,700 patients with a total of 50 different tumor types. Xgeva showed superior results in reducing SREs compared to Zometa in patients with breast or prostate cancer and bone metastasis. In patients with bone metastases due to other solid tumors, Xgeva showed results equal or superior to Zometa. The most serious adverse events included dyspnea, low blood calcium levels, and osteonecrosis of the jaw. Patients should be given calcium and vitamin D as need to prevent hypocalcemia. Xgeva has not been approved for patients with multiple myeloma or other cancers of the blood. To learn more, read the prescribing information for Xgeva.

Duloxetine HCl (Cymbalta®) — Approved for Chronic Musculoskeletal Pain
In November 2010 the FDA granted Eli-Lilly approval of Cymbalta to treat chronic musculoskeletal pain, including the discomfort of chronic low back pain and osteoarthritis. Cymbalta was originally approved in 2004 as an antidepressant and, more recently, as treatment for the symptoms of fibromyalgia. This new approval to treat musculoskeletal pain was based on 4 double-blind, placebo-controlled, randomized clinical trials with more than 600 patients. Results showed a significant reduction in pain compared with placebo. The recommended dose is one 60 mg capsule taken daily. Commonly reported side effects were nausea, dry mouth, insomnia, drowsiness, constipation, fatigue, and dizziness. Serious adverse events occurred in less than 1% of patients and included liver damage, allergic reactions, pneumonia, depressed mood, and suicidal thoughts and behavior. Read the prescribing information and medication guide for full administration and safety recommendations.

Acetaminophen IV (Ofirmev™) — Approved for Acute Pain and Fever Reduction
Ofirmev received FDA approval in November 2010 for the management of mild to moderate pain, the management of moderate to severe pain with an adjunctive opioid analgesic, and fever reduction. Cadence Pharmaceuticals reported that this first intravenous formulation of acetaminophen was approved on the basis of significant efficacy in 3 clinical trials conducted in adult and pediatric populations. Ofirmev is administered as a 15-minute IV infusion only and is available in 100 mL glass vials containing 1000 mg acetaminophen (10 mg/mL). The product is contraindicated in patients with a hypersensitivity to acetaminophen and those with severe hepatic impairment or active liver disease. Common adverse reactions in adult patients treated in clinical trials were nausea, vomiting, headache, and insomnia. Pediatric patients also experienced constipation, pruritus, agitation, and atelectasis (lung collapse). Ofirmev is expected to be available during the first quarter of 2011; complete administration and safety data can be found in the prescribing information.

Propoxyphene-Containing Analgesics (Darvon®, Darvocet®) Withdrawn Due to Cardiotoxicity Risk
Xanodyne Pharmaceuticals voluntarily agreed to stop marketing propoxyphene following the release of FDA data showing that serious cardiac toxicity may occur even at therapeutic doses. A new study reported an increased risk for serious heart rhythm abnormalities. The FDA has asked healthcare practitioners to contact their patients taking propoxyphene-containing drugs, to inform them of the risks, and to ask them to agree to discontinue the product in favor of alternative pain management treatment. They were also asked to stop new prescribing of these products. The FDA has requested that all other manufacturers of propoxyphene-containing generic drugs withdraw their products. Read the FDA Drug Safety Communication for full information; also see our blogpost Propoxyphene Products Withdrawn in USA. Why?