Vardenafil Will Compete for Share of ED Market

Pharmacology Watch

The FDA has approved vardenafil (Levitra—Bayer and GlaxoSmithKline) for the treatment of erectile dysfunction in men. Vardenafil joins sildenafil (Viagra) as the only 2 drugs approved for this indication in this country. Vardenafil was approved after trials involving more than 2009 men were presented to the FDA, including trials of men with diabetes and men who had undergone radical prostatectomy. The recommended dose is 10 mg taken one hour before sexual activity. Doses up to 20 mg may be taken if the 10 mg strength is inadequate. Lower doses (2.5 mg and 5.0 mg) are also available for men requiring lower doses due to drug interactions or other medical conditions. Vardenafil carries the same warning as sildenafil regarding concomitant use with nitrates or alpha-blockers, since this combination may cause dangerously low blood pressure. The drug should also not be taken by men who have QT prolongation. Vardenafil will be marketed as being a faster-acting, longer-lasting alternative to sildenafil.

Study Challanges Statin/Depression Link

The wholesale use of statins in otherwise healthy patients with elevated cholesterol levels has concerned many physicians because of decade-old studies linking statins with depression and violent behavior. A new study challenges those findings, and in fact asserts the opposite, suggesting that statins reduce the risk of psychological disorders including depression. Researchers from Harvard looked at 140 patients at an outpatient cardiology clinic who were treated with statins, compared to 231 control patients who were not on statins. Over an average follow-up of 4 years, statin use was associated with the 30-40% lower risk of abnormal depression scores (odds ratio, 0.63), anxiety (OR, 0.69), and hostility (OR, 0.77) after adjustment for potential cofounders. The improvement in psychological scores was independent of the cholesterol-lowering effect of the statins. The choice of statin was not defined in the report, but the authors make the comment that "the lipophilic statins, as opposed to all other cholesterol-lowering drugs, appear primarily responsible for the observed effect on psychological well-being." They further state "this hypothesis requires further testing." (J Am Coll Cardiol. 2003;42:690-697). The implication here is that lipophilic statins more readily cross the blood brain barrier where they exert their beneficial psychological effect.

Antibiotics, Placebo No Different in Rhinosinusitis Patients

Adult patients with rhinosinusitis do no better with antibiotics than placebo, according to a new study. Researchers from Switzerland randomized 252 adults with a history of purulent nasal discharge and facial pain to amoxicillin/clavulanic acid (Augmentin 875) or placebo twice daily for 6 days. There was no difference between the 2 groups in time to cure (hazard ratio for amoxicillin/clavulanate, 0.99; 95% CI, 0.80-2.05). There was also no difference in the days with restrictions due to rhinosinusitis, or in the number of patients with a positive rhinoscopy. Patients given amoxicillin/clavulanate were more likely to develop diarrhea at 7 days (odds ratio, 3.89; 95% CI, 2.09-7.25). The authors point out that rhinosinusitis is one of the most common indications for antibiotics in general practice and suggest that antibiotics can be safely withheld during the first week, a policy that may cut down on the emergence of antibiotic resistance (Arch Intern Med. 2003;163:1793-1798).

Rosuvastatin Approved for Lowering Cholesterol

The FDA has approved AstraZeneca’s rosuvastatin (Crestor) for marketing in this country. The new cholesterol-lowering statin was approved in doses ranging from 5 to 40 mg. The higher dose had been the subject of some controversy because of possible renal side effects, but the final labeling for the drug does not recommend kidney monitoring except the recommendation to screen for proteinuria. In studies presented to the FDA, rosuvastatin lowered LDL cholesterol by 45-63%, and increased HDL cholesterol by 8-14%, numbers similar to the effect of the current leader in the statin market, atorvastatin (Lipitor). AstraZeneca is planning a quick rollout of Crestor and is expected to heavily market the drug to compete with atorvastatin for this multibillion-dollar market.

Losartan More Effective Than Atenolol in Cardiovascular Treatment

In hypertensive patients without evidence of vascular disease, losartan is more effective than atenolol in preventing cardiovascular morbidity and mortality, according to a new study published in the Annals of Internal Medicine. As part of the ongoing Losartan Intervention for Endpoint reduction in hypertension (LIFE) study, 6886 men and women age 55-80 years of age with hypertension and evidence of LVH on electrocardiogram, but no evidence of vascular disease, were randomized in a double-blind fashion to once-daily treatment with losartan or atenolol. End points were cardiovascular deaths, stroke, or myocardial infarction. Blood pressure reduction was similar both groups. The primary composite end point occurred in 282 patients in the losartan group (17.5/1000 patient years) and 355 in the atenolol group (21.8/1000 patient years) (RR, 0.81; 95% CI, 0.69-0.95; P = 0.008). Other end points included cardiovascular deaths, 103 losartan group, 132 atenolol group (RR, 0.80 [CI , 0.62-.04]; P = 0.092), nonfatal and fatal stroke, 125 losartan group, 193 atenolol group (RR, 0.66 [CI, 0.53-0.82]; P < 0.001), and fatal and nonfatal myocardial infarction, 110 losartan group, 100 atenolol group (RR, 1.14 [CI 0.87-1.49]; P > 0.2). As in other studies of ARBs, new onset diabetes occurred less often in the losartan group. The authors conclude that in relatively low-risk patients without evidence of vascular disease, losartan is more effective than atenolol in preventing cardiovascular morbidity and mortality. They postulate that this effect may have a relationship to the vasculotoxic effects of angiotensin II out of proportion to the blood pressure lowering effects of the drug (Ann Intern Med. 2003;139:169-177).

Estradiol May Prevent Osteoporosis While Avoiding Adverse ERT Effects

A new study suggests that ultra low-dose estradiol may prevent osteoporosis while avoiding most of the adverse effects of estrogen replacement therapy. Researchers from the University of Connecticut randomized 167 healthy women older than 65 to micronized estradiol 0.25 mg per day or placebo in a double-blind fashion. Women who had not had hysterectomies also received micronized progesterone 100 mg per day. Bone mineral density (BMD) of the hip, spine, wrist, and total body were measured annually for 3 years, as were serum and urine biochemical markers of bone resorption and formation, and sex hormones. BMD increased at all sites for patients taking low-dose estradiol compared with placebo (P < 0.001), and markers of bone turnover were significantly reduced in the estradiol group as well. There was no difference between the 2 groups in breast tenderness, endometrial thickness or pathological effects, or mammographic findings. No breast cancers were found in either group during the study (JAMA. 2003;290:1042-1048). Two important questions, which deserve further investigation, are raised by the study and include whether the adverse events found with HRT in the Women’s Health Initiative can be prevented by lower doses of estrogen, and whether estradiol or any other estrogen product, or other estrogen/progestin combinations are safer than conjugated estrogen/medroxyprogesterone, which was used in the WHI study.

Other FDA Actions

Bayer has received FDA approval to market a once-a-day formulation of ciprofloxacin for the treatment of complicated urinary tract infections. The 1000 mg once daily for the drug will be called Cipro XR. The company is expected to lose patent exclusivity on its other formulations of ciprofloxacin in 2004.

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: 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.