Pharmacology Watch
November 1, 2006 5 minutes read
Wait and See Prescriptions for Treatment of Otitis Media
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Wait and see prescriptions (WASP) is a new concept for the treatment of otitis media in children. Children with otitis media frequently improve without antibiotics, and antibiotic overuse may be avoided with WASP, where prescriptions are given to parents but only filled if symptoms persists or worsen after 48 hours. This approach was evaluated in a recent study from the University of Oregon. In an urban, emergency room setting, 283 children with acute otitis media were randomized to WASP or standard therapy with an antibiotic. Sixty-two percent of parents in the WASP group did not fill their prescriptions, while 13% of parents in the standard therapy group did not fill theirs (P < .001). There was no statistically significant difference in the frequency of subsequent fever, otalgia, or unscheduled visits for medical care between the 2 groups. Very sick or toxic children were excluded from the study.
The authors conclude that wait-and-see prescriptions substantially reduce unnecessary use of antibiotics in children with acute otitis media (JAMA. 2006;296:1235-1241). In an accompanying editorial, Paul Little, MD, from University of Southampton in England, discusses how wait-and-see prescriptions for otitis media have been adopted by many northern European countries. He praises the current study because it was done in the emergency room setting where there is no ongoing relationship with a physician, and the chance for poor outcomes may have been higher. He also states that "If parents are given clear information about the timing of antibiotic use and specific guidelines for signs and symptoms that should trigger reassessment, delayed prescribing probably has its place, should be acceptable to parents, appears reasonably safe, and provides a significant step in the battle against antibiotic resistance" (JAMA. 2006;296:1290-1291).
New Hope for Macular Degeneration?
Two studies in the October 5th New England Journal of Medicine evaluate a new treatment for macular degeneration. Ranibizumab is a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A (VEGF-A), which has been implicated in promoting neovascularization. Administration of the drug involves a monthly intravitreal injection. In the first study, 716 patients were enrolled and randomized to 2 different doses of ranibizumab or sham injections. In both the low-dose and high-dose ranibizumab (0.3 mg and 0.5 mg, respectively), loss of visual acuity was significantly slowed compared to sham injections (P < 0.001 for both doses), and visual acuity actually improved by 15 or more letters in 25% of the 0.3 mg group and 34% of the 0.5 mg group, as compared to 5% of the sham injection group (P < 0.001 for both doses). The benefit in visual acuity was maintained for 24 months. Side effects were uncommon (N Engl J Med. 2006; 355:1419-1431).
In the second study, ranibizumab (0.3 mg or 0.5 mg) was compared to verteporfin photodynamic therapy. Significantly more patients lost fewer than 15 letters in the ranibizumab group vs verteporfin group (96.4% vs 64.3%, P <0 .001 for each comparison). Visual acuity improved by 15 letters or more in both ranibizumab groups (35.7% for 0.3 mg group and 40.3% for 0.5 mg group) vs 5.6% for the verteporfin group (P < 0 .001 for each comparison). Mean visual acuity increased in both ranibizumab groups, and decreased significantly in the verteporfin group. Side effects were uncommon in both groups.
The authors conclude that ranibizumab is superior to verteporfin for treatment of neovascular age-related macular degeneration (N Engl J Med. 2006:355:1432-1444). An accompanying editorial (N Engl J Med. 2006;355:1493-1495) and perspective (N Engl J Med. 2006;355:1409-1412) raise a fascinating ethical and economic issue regarding this issue.
Ranibizumab was recently approved by the FDA for use for macular degeneration under the trade name Lucentis (Genentech). The wholesale cost for the 0.5 mg monthly injection is $1950. Prior to the approval of ranibizumab, many ophthalmologists began compounding bevacizumab — a closely related monoclonal antibody also manufactured by Genentech and marketed under the trade name Avastin for the treatment of colorectal cancer — and using it as an intravitreal injection. The drug is formulated as an intravenous formulation, and the use of bevacizumab for macular degeneration is off label, but the drug seems to be effective based on several case studies. There is also a chance that bevacizumab may last longer in the eye since it is a much larger molecule. The cost of a single injection is also between $20 and $50. The economics alone make this issue of interest; however, it is unlikely that Genentech will intentionally undermine its own drug with a less expensive alternative, so we may not see company-sponsored studies on the use of bevacizumab for macular degeneration anytime soon.
Can Cialis be Used for Edema?
Erectile dysfunction drugs have significant effects on pulmonary vasculature, as evidenced by the recent approval of sildenafil for pulmonary hypertension. A new study suggests that tadalafil (Cialis) may be effective for preventing high-altitude pulmonary edema. In a small study from Europe, 29 adults with a history of high-altitude pulmonary edema were randomized to tadalafil 10 mg, dexamethasone 8 mg, or placebo twice daily during ascent and stage to 4559 m (14,000 feet). Two participants in the tadalafil group dropped out early because of acute mountain sickness but, of the remainder, high-altitude pulmonary edema developed in 7 of 9 participants receiving placebo, 1 of 8 adjustments receiving tadalafil, and none of the 10 participants receiving dexamethasone (P = 0.0074 for tadalafil, P < 0.001 for dexamethasone).
The authors conclude that both dexamethasone and tadalafil decrease pulmonary artery pressures and reduce the incidence of high-altitude pulmonary edema in patients at risk, although dexamethasone may be somewhat more effective (Ann Int Med. 2006;145:497-506).
FDA Actions
Novartis is warning doctors about the risk of congestive heart failure associated with its anticancer drug imatinib (Gleevec). The company is sending a letter to US and Canadian physicians as a result of an article in Nature Medicine that reported 10 patients had developed cardiotoxicity associated with use the drug (Nature Medicine. 2006;12:908-916). Patients with a history of high blood pressure, diabetes, or a history of heart disease may be particularly at risk.
Once a day amoxicillin is a reasonable alternative to twice a day dosing for children with strep pharyngitis, according to a new study. In 652 children with pharyngitis, researchers compared 750 or 1000 mg (depending on weight) once daily doses vs twice-a-day standard dosing. Failure rates by culture were 20.1% in the once daily group and 15.5% in the twice daily group; however, failure rates were lower in the once daily group at 28 days. There were no significant differences in adverse events (Pediatric Infect Dis J. 2006;25:761-767).
Mirtazapine may be a safe antidepressant for pregnant women. In 77 live births exposed to mirtazapine in the first trimester, there were 2 major malformations, a rate that is not significantly higher than chance. The drug was associated with a higher rate of preterm birth and spontaneous abortion, as noted with other antidepressants (J Clin Psychiatry. 2008:67:1280-1284).
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. 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. Questions and comments, call: (404) 262-5416. E-mail: [email protected].
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