The new maximum daily dose (MDD) of acetaminophen will soon be six dosage units (3,000 mg) for all Tylenol and acetaminophen-containing products, a reduction from the current MDD of eight dosage units (4,000 mg), says McNeil Consumer Healthcare of Johnson & Johnson.1 The MDD lowering recommendations are intended to reduce accidental overdoses from over-the-counter acetaminophen-containing products. In January, the U.S. Food and Drug Administration (FDA) asked manufacturers of prescription products to lower the total amount of acetaminophen in dosage forms to no greater than 350 mg. Both the MDD change and the maximum dosage change are planned for 2012. Prescribers and patients themselves are often unaware of the total daily acetaminophen amount that is consumed. This is often due to different products containing varied amounts. Hepatotoxicity from acetaminophen is more common than many prescribers realize, and this effort aims to improve medication safety.
Dronedarone, an antiarrhythmic agent approved by the FDA in July 2009, is used to reduce the risk of cardiovascular hospitalization in patients who are in sinus rhythm or who will be cardioverted but who also have paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors.2 The FDA is reviewing clinical trial data in patients with permanent AF, including data from one study that was terminated early after a twofold increase in death and a twofold increase in stroke and hospitalization for heart failure was noted. There were 32 deaths in the dronedarone arm and 14 in the placebo arm (P=0.009). The objective of the this study, known as PALLAS, was to assess the potential benefit of dronedarone 400 mg twice daily in patients over 65 years old with permanent AF in the reduction of major cardiovascular events (stroke, systemic arterial embolism, myocardial infarction [MI], or cardiovascular death), unplanned cardiovascular hospitalization, or any cause of death. It is not clear how these results affect patients using dronedarone for its FDA-approved indications.
As recently reported in an ACR Hotline released June 29, 2011, rituximab was the subject of a Health Canada Safety Advisory related to information regarding fatal infusion reactions in rheumatoid arthritis (RA) patients.3 Officials reported that it was unclear whether patients were premedicated prior to rituximab infusion because analgesics, corticosteroids, and antihistamines are recommended prior to these infusions. They noted that health professionals should remain attentive for signs of hypersensitivity or anaphylactic reactions in patients receiving rituximab infusions and report any spontaneous reactions to authorities (e.g., the FDA Adverse Event Reporting Program, Health Canada).
New Drug and Device Information
A new subcutaneous injectable formulation of abatacept (Orencia) to treat moderate to severe RA in adults is slated to become available later this month.4 This new formulation was compared to the already available intravenous formulation and showed similar efficacy and safety at six months.
Adalimumab (Humira) may soon be used to treat ulcerative colitis because studies have shown that patients taking it had a higher remission rate than placebo-treated patients.5 The FDA is expected to rule in on this use toward the end of this year or in early 2012. It is also being investigated to treat uveitis, hidradenitis suppurativa, and other conditions. Adalimumab faces competition from oral agents for RA and other oral agents for similar immune-mediated diseases. Abbott is also planning to apply for FDA approval to sell adalimumab with a thinner needle to try to reduce patient discomfort. The manufacturer plans to have the smaller needle packaged with the pen devices and with the prefilled syringes.
The first ceramic-on-metal total artificial hip implant for treating patients with osteoarthritis (OA) was recently FDA approved.6 It is known as the Pinnacle CoMplete Acetabular Hip System and is the first to combine a ceramic ball and a metal socket. Prior approved devices have used combinations of metal, ceramic, and polyethylene plastic. This approval was provided subsequent to a two-year, randomized clinical trial that compared 194 patients who received the new hip implant to 196 patients who received a metal-on-metal hip implant. Two patients who received the Pinnacle CoMplete system required a second surgery to replace their new implant compared with three patients who required a second surgery in the control group. Clinically there were differences between the groups following the hip surgery. Contingent on their approval, the manufacturer is required to conduct a postmarketing study for adverse event and metal ion blood concentrations.
Oxycodone (Oxecta) has been approved by the FDA to treat patients with acute and chronic moderate-to-severe pain where the use of an opioid analgesic is appropriate.7 This agent is the first oxycodone immediate-release formulation that is designed to discourage common methods of tampering such as crushing or dissolving, which are associated with opioid abuse and misuse. This oxycodone also causes nasal irritation if snorted. The manufacturer is being required to conduct a study to determine whether this analgesic decreases consequences of abuse and misuse. It is expected to be available before the end of 2011.
Rivaroxaban has been FDA approved for the prevention of deep vein thrombosis in patients undergoing hip or knee replacement surgery.8 It is currently the only new oral anticoagulant for venous thromboembolism prophylaxis in patients undergoing knee or hip replacement surgery. In clinical trials, rivaroxaban was more effective than enoxaparin and placebo, with a similar safety profile compared to enoxaparin as well as lower major bleeding rates. Approval is also being sought for stroke prevention in AF.
Ticagrelor, another oral antiplatelet agent, recently garnered FDA approval for reducing thrombotic events in patients with acute coronary syndrome, including unstable angina, and patients with MI who are stenting candidates.9 Ticagrelor was studied in a dual antiplatelet regimen and comes with a boxed warning that aspirin doses greater than 100 mg daily can decrease its effectiveness. A Risk Evaluation and Mitigation Strategy was part of its approval, as has been the case with other recently FDA-approved antiplatelet agents. The agent was compared to clopidogrel, which had slightly lower bleeding rates. Clopidogrel is expected to lose patent protection in May 2012.
AN2728 is a boron-based small molecule that inhibits phosphodiesterase-4 activity, thereby reducing the production of tumor necrosis factor–alpha, interleukin (IL)-12, IL-23, and other proinflammatory cytokines. It has received positive results from a phase IIb trial in psoriasis patients.10 It was studied in 68 patients with mild to moderate plaque-type psoriasis in a 12-week study and was compared with a placebo vehicle. A Physician’s Global Assessment score was used to determine outcomes. AN2728-treated patients showed improvement compared to placebo at all recorded time points during the study, with peak efficacy occurring after Day 42 of treatment. AN2728 is a 2% topical ointment. Phase III trials are planned.
BT-061 is an anti-CD4 antibody undergoing a phase II clinical trials for the treatment of RA and psoriasis.11 It is also undergoing preclinical trials for other immune-mediated diseases. Abbott has entered into a partnership agreement with Biotest to develop and market this agent, to strengthen the Abbott immunology pipeline.
Canakinumab, an investigational IL-1-beta protein targeted monoclonal antibody, was deemed not approvable for acute gouty attacks by the FDA’s Arthritis Advisory Committee.12 Safety issues, such as increased infection rates and high triglyceride levels, were of concern, considering it was felt that the agent would mainly be used for symptomatic relief rather than as a disease-modifying agent. The drug is already approved for use in patients with cryopyrin-associated periodic syndrome.
IMO-3100, an investigational TLR7 and TLR9 antagonist for psoriasis, is currently on clinical hold for proposed phase II clinical trials.13 A clinical hold, which is requested by the FDA, is used to delay a proposed trial or suspend an ongoing clinical trial. More data should be available soon.
Michele Kaufman is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.
- DeNoon DJ, Martin L. New dosing labels for extra strength Tylenol maximum dosage will be reduced to 6 pills a day. www.webmd.com/pain-management/news/20110728/new-dosing-labels-for-extra-strength-tylenol. Published July 28, 2011. Accessed July 28, 2011.
- FDA Drug Safety Communication: Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events. www.fda.gov/Drugs/DrugSafety/ucm 264059.htm. Published July 21, 2011. Accessed July 27, 2011.
- RITUXAN (rituximab)—fatal infusion related reactions in patients with rheumatoid arthritis—for health professionals. http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2011/ rituxan_6_hpc-cps-eng.php. Published June 2, 2011. Accessed June 29, 2011.
- Dennis M. FDA clears new formulation of Bristol-Myers Squibb’s arthritis drug Orencia. www.firstwordpharma.com/forward/emailref?path=node/894126. Published July 31, 2011. Accessed August 2, 2011.
- Loftus P. Abbott seeks improvements for Humira. www.marketwatch.com/story/abbott-seeks-improvements-for-humira-2011-06-21. Published June 21, 2011. Accessed July 28, 2011.
- FDA approves first ceramic-on-metal total hip replacement system. www.medicalnewstoday.com/releases/228502.php. Published June 16, 2011. Accessed July 28, 2011.
- Dennis M. FDA approves Pfizer, Acura’s pain drug Oxecta. www.firstwordpharma.com/node/879810. Published June 20, 2011. Accessed July 28, 2011.
- Dane L. FDA approves Johnson & Johnson, Bayer’s Xarelto for DVT. www.firstwordpharma.com/node/883881. Published July 1, 2011. Accessed July 28, 2011.
- Peck P. FDA okays new drug to prevent death, MI. www.medpagetoday.com/Cardiology/PCI/27647. Published July 20, 2011. Accessed July 22, 2011.
- Anacor Pharmaceuticals announces positive preliminary results from Phase 2b trial of AN2728 for psoriasis. http:// inves tor.anacor.com/releasedetail.cfm?RELEASEID=587511&. Published June 27, 2011. Accessed July 28, 2011.
- Dennis M. Abbott, Biotest enter deal for rheumatoid arthritis, psoriasis drug. www.firstwordpharma.com/forward/emailref?path=node/880228. Published June 21, 2011. Accessed July 28, 2011.
- Gever J. FDA panel calls biologic drug unsafe for gout. www.medpagetoday.com/Rheumatology/Arthritis/27195?utm_source=breaking-news&utm_medium=email&utm_campaign=breaking-news. Published June 21, 2011. Accessed June 21, 2011.
- Idera reports clinical hold on proposed Phase 2 clinical trial of IMO-3100. http://ir.iderapharma.com/phoenix.zhtml?c=208904&p=irol-newsArticle_print&ID=1587275&highlight=. Published July 20, 2011. Accessed July 28, 2011.