FDA Approves Claritin For OTC Use For Seasonal Rhinitis

Pharmacology Watch

After years of legal wrangling, the FDA has approved loratadine (Claritin, Schering-Plough) as an over-the-counter (OTC) product for the treatment of seasonal rhinitis. Loratadine is considered a nonsedating antihistamine, and its OTC approval was linked with the FDA's work with the National Transportation Safety Board to improve public awareness about the concerns of drowsiness while driving associated with older antihistamines. The OTC switch also comes within months of loss of patent protection for loratadine and the entry into the market of generic equivalents. The OTC switch applies to all 5 formulations of Claritin, and at least 1 generic house plans to market "Reditabs." Meanwhile, Schering-Plough continues to aggressively market desloratadine, the active metabolite of loratadine under the trade name Clarinex, in an attempt to protect its $3 billion Claritin market.

Simpler Atrial Fibrillation Management

Management of atrial fibrillation (AF) may be simpler in the future based on the results of 2 studies published in the December 5, 2002, N Engl J Med. The larger of the 2 studies (AFFIRM) enrolled more than 4000 patients in the United States and Canada with AF and at least 1 other risk factor for stroke such as hypertension, coronary artery disease, diabetes, congestive heart failure, or age older than 65. Patients were randomized to a rhythm control strategy with cardioversion followed by amiodarone, sotalol, propafenone, or older antiarrhythmics such as procainamide or quinidine; or a rate control strategy with digoxin, beta-blockers, and/or calcium channel antagonists. All patients in both groups were anticoagulated with warfarin. The primary end point was overall mortality. The 5-year death rate was 23.8% in the rhythm control group and 21.3% in the rate control group (P = 0.08). Rhythm control was associated with more hospitalizations and more adverse drug effects. In the second study from The Netherlands, 522 patients with persistent AF after electrical cardioversion were randomized to treatment aimed at rate control or rhythm control. Both groups received oral anticoagulation, and the composite end point was death from cardiovascular causes as well as bleeding, implantation of a pacemaker, or severe adverse effects of drugs. After a mean duration of nearly 2.5 years, the primary end point occurred in 44 patients in the rate control group (17.2%) and 60 patients in the rhythm control group (22.6%) (P = 0.11). Although both studies showed trends toward adverse outcomes with rhythm control, neither study reached statistical significance. The authors of both studies suggest that a rate control strategy for the treatment of AF is at least as good as the rhythm control strategy. In an accompanying editorial, Michael D. Cain, MD, states that "on the basis of these data, rate control can now be considered a primary approach to the treatment of atrial fibrillation." He also suggests that nonpharmacologic treatments for AF will still be pursued with the goal toward maintaining sinus rhythm (N Engl J Med. 2002;347:1825-1833; 1834-1840; 1883-1884).

Oral Anticoagulation Vs Aspirin in AF

In a related study, oral anticoagulation was found to be superior to aspirin in preventing stroke in patients with atrial fibrillation (AF) or paroxysmal AF. The study was a pooled analysis of 6 trials of more than 4000 patients who were randomized to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. Patients receiving oral anticoagulation were significantly less likely to experience stroke (2.4 vs 4.5 events per 100 patient years; hazard ratio [HR], 0.55), ischemic stroke (HR, 0.48), or cardiovascular events (HR, 0.71) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient years; HR, 1.71). Anticoagulant therapy also showed benefit on all-cause mortality but only after 3 years of therapy. Interestingly, more benefit was seen for anticoagulation vs aspirin in patients younger than 75 compared to those 75 years or older. A lesser benefit was also seen for women compared to men. The authors suggest that oral anticoagulation is more effective than aspirin in decreasing the risk of stroke and other cardiovascular events in patients with nonvalvular AF (JAMA. 2002;288:2441-2448).

Immunization Does Not Cause Autism

A new study should put an end to concern regarding the MMR (measles, mumps, and rubella) vaccine and its possible link to autism. Researchers in Denmark looked at the records of all children born between January 1991 and December 1998, representing a cohort of almost 540,000 children. Of those, 82% (440,655) received the MMR vaccine. In the cohort, 316 children were diagnosed with autism and 422 were diagnosed with other artistic spectrum disorders. After adjustment for potential confounders, the relative risk for artistic disorder in the vaccinated children compared to the unvaccinated was 0.92 (95% CI, 0.68 to 1.24). The relative risk for other artistic spectrum disorders was 0.83 (95% CI, 0.65 to 1.24). The authors also looked for a possible association between age at the time of vaccination, the time since vaccination or the date of vaccination, and development of artistic disorder and found no relationship. They also found no temporal clustering of cases of autism at any time after immunization (N Engl J Med. 2002;347:1477-1482).

Statins May Lower CRP Levels

C-reactive protein (CRP), an inflammatory marker, has shown to be a strong predictor of cardiovascular events, perhaps even more predictive then LDL cholesterol levels (N Engl J Med. 2002; 347:1557-1565). Most physicians have looked at these studies with interest but have been unsure what to do with an elevated CRP level in an individual patient. Perhaps even more importantly, it is unclear whether lowering CRP affects cardiovascular outcomes. Until an answer is found to this important question, an increasing body of evidence is suggesting that statins may lower CRP levels.

Simvastatin Reduced CRP Plasma Levels

A recent study reviewed the use of simvastatin in 130 patients with mixed hyperlipidemia and 195 patients with hypertriglyceridemia in a placebo-controlled, double-blind trial. After 6 weeks of treatment with simvastatin 20, 40, and 80 mg, significant reductions in CRP plasma levels were noted vs placebo (P < 0.05) (Am J Cardiol. 2002;90:942-946). CRP lowering by statins appears to be a class effect with multiple reports of benefit with various statins in the last 2 years.

FDA Actions

Roche’s pegelated interferon alfa-2a (Pegasys) has been approved for use in combination with a ribavirin for the treatment of hepatitis C. The drug was approved in October 2002, but Roche has been eagerly awaiting the approval for combination treatment in order to compete with Schering-Plough’s Peg-Intron/ribavirin combination for the same indication.

Eli Lilly has received approval to market atomoxetine (Strattera) for the treatment of attention deficit hyperactivity disorder (ADHD). Unlike other drugs for this indication, atomoxetine is not a stimulant and is not listed as a controlled substance. Rather, the drug is a selective norepinephrine reuptake inhibitor, which seems to play a role in regulating attention, impulsivity, and activity levels. Strattera is approved for treatment of ADHD in children, adolescents, and adults.

Eli Lilly has also received approval to market teriparatide injection (Forteo) for the treatment of osteoporosis in postmenopausal women who are at high risk for fracture. Teriparatide is a portion of human parathyroid hormone, which stimulates new bone formation in the spine and hip. The drug is given by daily injection in the thigh or abdomen. 


This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. Telephone: (404) 262-5517. E-mail: robin.mason@ahcpub.com. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.