U.S. Pharmacist

A compound designed to prevent chest pains in heart patients has shown promising results in animal studies, say scientists. In the second issue of the British Journal of Pharmacology to be published by Wiley-Blackwell, researchers from the Centre de Recherche Pierre Fabre in France, show that the novel compound F15845 has anti-angina activity and can protect heart cells from damage without the unwanted side effects often experienced with other drugs.

Because F15845 does not interfere with heart function, as some conventional drugs such as beta blockers do, it could be given as part of a combination therapy. “It’s completely different from other anti-angina drugs which directly interact with the function of the heart. So the idea is to do a co-administration with conventional heart drugs such as beta blockers,” says lead author of the study, Bruno Le Grand from the Centre de Recherche Pierre Fabre in Castres, France.

The drug works by blocking excess influxes of sodium into heart cells through ‘gate’ proteins called sodium channels. High levels of sodium in heart cells are associated with low oxygen levels, which cause angina and can in turn lead to the build up of toxic concentrations of calcium that are lethal to cells. A number of drugs that target sodium channels can block the influx, but they act universally on heart cells and can sometimes cause further heart irregularities.

F15845 specifically targets the sodium channels that are thought to cause the most damage, those responsible for what is known as the persistent sodium current, which causes a permanent excess sodium influx.

The study confirmed the drug’s anti-angina activity in laboratory animals. The researchers say the drug is absorbed well when given orally and represents a novel therapeutic opportunity for treating angina and possibly other cardiac pathologies.

“We know that in animals, we have acceptable bioavailability, but with the data that we have in human volunteers following phase I clinical trials we are very confident that it is above 70 per cent,”

Retail pharmacies “are waging what some consider a generic-drug price war that is threatening margins in a typically high-profit area and reflects the intense competition that drug store chains face in attracting and keeping customers,” the Wall Street Journal reports. According to the Journal, generic drug programs have “proliferated” since Wal-Mart in 2006 began selling a month’s supply of many generic prescriptions for $4. Now, large pharmacy chains such as Walgreen, CVS Caremark and Rite Aid have begun to “aggressively promote their discount drug programs … as the economy declined and competition increased,” the Journal reports. According to the Journal, “These moves are among the latest in a market battle that has helped lead to lower prices and greater use of generic drugs.”

This summer, Walgreen strengthened marketing for its Prescription Savings Club, which provides customers with discounts on generic drugs and 5,000 brand-name medications, as well as rebates on store-brand products. CVS this fall introduced a discount program for uninsured customers that offers a 90-day supply of more than 400 generic drugs for $9.99 and a 10% discount at the company’s store-based health clinics. In September, Rite Aid unveiled a prescription savings card that offers hundreds of generic drugs at $8.99 for a 30-day supply or $15.99 for a 90-day supply, in addition to discounts on brand-name drugs and store-brand products. Rite Aid CEO Mary Sammons in September acknowledged that the programs were beginning to affect consumers’ decisions about where to purchase medications, the Journal reports.

Kermit Crawford, senior vice president of pharmacy at Walgreen, said, “I don’t know if I would term it a generic price war,” adding, “I think that the pricing is competitive within certain therapeutic categories, and I think what you see is all of the retailers promoting their competitive price.” Carolyn Castel, CVS spokesperson, said, “The prevailing economic situation only increases the need to offer options” for the underinsured and uninsured.

Pharmacy benefit managers such as CVS, Medco Health Solutions and Express Scripts, which administer large U.S. mail-order pharmacies, said retail generic discount programs are not hurting their businesses. Medco Vice President for Channel and Generic Strategy Ken Malley said, “The movement’s really been from retail to retail. We have not seen movement from our mail pharmacies.” He added that mail-order programs mostly serve the insured, while retail programs tend to focus on uninsured patients. He also noted that generic drug prices for the insured already are low (Wisenberg Brin, Wall Street Journal, 12/22).

U.S. Attorney Matt M. Dummermuth announced recently that an officer of an Internet pharmacy business who failed to report more than $1.6 million in income to the IRS was sentenced Nov. 25, 2008, to three years’ imprisonment.

Alexis Avello, 42, of Coral Gables, Fla., received the prison term after pleading guilty June 6, 2008, to willfully filing a false tax return. At the plea hearing, he admitted he falsely filed a federal income tax return in 2005 in which he claimed his taxable income for 2004 was $5,929.

Avello eventually admitted his taxable income in 2004 was really more than $1.6 million. Avello agreed as part of the plea agreement to litigate the civil forfeiture of more than $3.8 million he received from Pharma.com, an Internet pharmacy business for which he was a corporate officer until early 2004.

He was sentenced in Cedar Rapids by United States District Court Chief Judge Linda R. Reade. Avello was sentenced to 36 months’ imprisonment and ordered to pay the costs of prosecution — more than $61,400. A special assessment of $100 was imposed, and he was ordered to make $558,566 in restitution to the IRS for the tax loss that resulted from his false return. He must also serve a one-year term of supervised release after the prison term.

Avello is being held in the U.S. Marshal’s custody until he can be transported to a federal prison. The case was prosecuted by Assistant United States Attorneys Stephanie M. Rose and Matthew J. Cole and was investigated as part of the Organized Crime Drug Enforcement Task Force program of the United States Department of Justice through a cooperative effort of the Drug Enforcement Administration Office of Diversion Control, the Internal Revenue Service, and the Dubuque Drug Task Force.

Pfizer has dropped its bid to market its potency pill Viagra over the counter in Europe, the US pharmaceutical giant announced Thursday.

Pfizer “has withdrawn its application to switch the legal status of the 50 mg tablet strength of Viagra from ‘prescription only’ to ‘non-prescription’ in the European Union (EU),” a statement said.

Prizer said it had decided to withdraw the application “to fully consider” comments from the European Medicines Agency‘s Committee for Medicinal Products for Human Use, “recognizing that there were some concerns regarding the proposed supply of Viagra 50 mg tablets without a prescription,” the statement said.

“All current doses of Viagra will continue to be available to patients by prescription from their doctor,” it said.

Worldwide sales of Viagra, first introduced ten years ago, reached 1.8 billion dollars in 2007.

About 5 million Americans attend meetings of self-help groups like Alcoholics Anonymous for alcohol and drug abusers, and nearly half of them reported remaining clean, a federal study released on Monday showed.

The U.S. Substance Abuse and Mental Health Services Administration examined the popularity of meetings like those run in many communities by AA and Narcotics Anonymous.

In these kinds of meetings, people speak to others who also are grappling with drug and alcohol abuse about their experiences and offer emotional support to one another as they try to beat their addiction.

The findings were based on a survey given to 135,672 people age 12 and older in 2006 and 2007, the agency said.

SAMHSA said 5 million people age 12 and older — 2 percent of the U.S. population in that age group — reported attending such a self-help group in the prior year because of alcohol or drugs. About two-thirds of them were male and 80 percent were over age 25.

Of those people, 45 percent reported abstaining from drugs and alcohol during the month before responding to the survey.

About a third of those who attended a self-help group also reported undergoing more formal treatment for addiction in the past year such as entering a formal rehabilitation facility.

Stephen Wing, the agency’s associate administrator for alcohol policy, said about 22 million Americans meet the definition for substance abuse. Wing said the agency did not have data on whether attendance at these types of meetings was increasing over time.

“The data reinforces the fact that participation in self-help groups is associated with abstinence and recovery,” Wing said.

Generics are copies of brand-name medicines whose patents have expired.That usually happens after a brand drug has been on the market for about
10 to 14 years. By law, the brand name company loses the right to be the only seller of that drug after its patent period is up. But it can be quite confusing
when new generics become available.The first reason for that confusion is that most of the time the brandname drug stays on the market. So if you have been taking one for many
years for a chronic disease, you and your doctor will have a choice: You can stick with the brand or switch to the generic. Not surprisingly, you may be reluctant
to switch at first because change isn’t easy if something is working. That’s one reason many generics remain under-prescribed compared to brands.But these days, your insurer,
pharmacist, and doctor may be newly committed to making the switch. Our advice: there’s no reason not to.The second reason generics can be confusing is that generic pills often
look different. The companies that make brand-name drugs have been very successful at selling you their pharmapills in certain colors, shapes, and sizes. For example, you may recall the
ads for the “purple pill” (for heartburn).Brand pills may also have a colored outer shell that contains a sweetener. Generics, in contract, areoften plain white pills that don’t look
as high quality. Our advice: don’t be fooled by appearances. The shape,color, and taste of a pill make no biological or medical difference.The third reason for confusion is that
many doctors may continue to write a prescription for the brand medicine and leave it to the pharmacist to ask you whether you would prefer that or the generic. In every state, the pharmacist
can make this switch without the doctor’s permission, but they must ask you first. The problem: when you get asked this question for the first time or for a new prescription, you may be
reluctant. Our advice: talk it over with the pharmacist and take the generic.

A new diet drug, tesofensine, produces twice the weight loss of currently available obesity drugs, Danish researchers report.

“Tesofensine produces a weight loss of approximately 10 percent more than placebo and diet in obese patients,” said lead researcher Dr. Arne Astrup, from the Department of Human Nutrition, Faculty of Life Sciences, at the University of Copenhagen. Other drugs produce only about 5 percent weight loss, Astrup noted.

This drug could replace the need for gastric bypass surgery in some obese patients. “There is an enormous gap between the existing weight-loss compounds and gastric surgery,” Astrup said. “Tesofensine could close that gap. If you combine the drug with an effective diet, you could probably reach the 20 percent weight loss seen in gastric surgery.”

“Tesofensine could compete with gastric surgery and be offered to those who are below the threshold for surgery or for patients who do not wish [to have] gastric surgery,” Astrup said. “There are also patients who cannot tolerate gastric surgery.”

The report was published in the Oct. 23 online issue of The Lancet.

For the study, Astrup’s team conducted a phase II trial in which they randomly assigned 203 obese patients to receive three different daily doses of tesofensine or placebo. The participants were also put on a low-energy diet.

Among the 161 who completed the trial, those who received tesofensine lost more weight than those receiving placebo. Over 24 weeks, those receiving the lowest dose of tesofensine (0.25 milligrams) lost 14.7 pounds, while those taking 0.5 milligrams lost 25 pounds, and those taking the highest dose (1 milligram) lost 28 pounds. People receiving placebo lost less than 5 pounds.

The weight loss among people who took 0.5 or 1 milligram of tesofensine was double that of weight loss seen with the currently available diet drugs Acomplia (rimonabant) or Meridia (sibutramine), the researchers said.

People taking the highest dose of tesofensine experienced a rise in blood pressure. Other side effects of the drug included dry mouth, nausea, constipation, hard stools, diarrhea and insomnia.

Astrup believes that the 0.5 milligram dose is the best, because it produced weight loss with the fewest side effects.

Early evidence shows that people who stay on the drug maintain their weight loss and may even continue to lose weight, Astrup said.

Once starting the drug, people would need to keep taking it to maintain the benefit, Astrup said. “There is no treatment that is working beyond its taking. This is true for all anti-diabetic medication, hypertension medication and everything, including anti-obesity drugs,” he said. “It’s a long-term treatment, and, in some cases, a permanent treatment to keep body weight down.”

Tesofensine works by inhibiting the neurotransmitters noradrenalin, dopamine and serotonin in the brain. In turn, this suppresses hunger, leading to an energy deficit which burns excess body fat. The drug’s effect was first noticed in trials involving Alzheimer’s and Parkinson’s patients.

Larger clinical trials of tesofensine are expected to begin next year, Astrup said.

Astrup noted that Neurosearch, the maker of tesofensine, is seeking approval for the drug in the United States and Europe. Astrup is a paid consultant for Neurosearch and also owns stock in the company.

Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine, thinks that the true test of any diet or drug is its ability to keep weight off over time.

“Losing weight, in the short term, though not easy, is not all that challenging,” Katz said. “Any diet that restricts choice will tend to work, from low fat, to low carb, to cabbage soup or grapefruit, and a number of drugs can provide this effect as well, including, it seems, tesofensine,” he said.

But the real test is sustainable weight control over the long term, Katz said. “This six-month study cannot tell us if tesofensine will pass that test,” he noted.

This trial did find that tesofensine increased heart rate and blood pressure slightly, and reduced lean body mass along with fat mass. “These effects are all of potential concern,” Katz noted.

“Additional study is needed to tell us what place tesofensine might occupy among the strategies available to facilitate sustainable, healthful weight loss,” Katz said. “Though promising, this study does not yet get us there.”

There was a time when discussions about sexual dysfunction were limited to the bedroom. Viagra brought it to the living room, and now every night, it and two rivals, Levitra and Cialis, battle on the airwaves.

viagra “Well, it’s a war, and it’s a very expensive war,” said Jim Mathews, of the Mathews Evans Advertising.

The competing drug makers are spending $300 million a year on advertisements, trying to tap into the 17 percent of men over 40 who experience erectile dysfunction.

“There’s a lot at stake. They’re projecting $6 billion in sales in this category by the year 2006, which is not all that far off,” Mathews said.

Urologist Dr. Dan Keiller credits the advertisements with prompting men to finally get help for what sometimes turns out to be an underlying condition, like diabetes or high cholesterol.

SURVEY
Men: Would you seek help for erectile dysfunction?
Yes, I already have.
Yes, I absolutely would.
Maybe, depending on how much it affected my life.
No, it would be too embarrassing.
I’m not sure.
Results | Disclaimer | E-Mail
“I think advertising, even though it has the ploy of selling medications has been wonderful for the community of men and getting us to speak about our health,” Keiller said.

Getting that discussion going without being vulgar or generating giggles is a challenge for the drug rivals, each trying to carve out a niche with different themes.

Although the three drugs are competing against each other, they’re not starting a price war because each pill still costs about $10. Instead, they are using advertising to try to increase their brand recognition.

Viagra focuses on depicting happy men in their ads. Levitra uses a woman’s testimonial and sports star Mike Ditka.

Cialis, which is more subtle and longer-lasting, focuses on the relationship.

The advertisements clearly tap into men’s insecurities, according to communication professor Ric Pierson.

“I think it’s sort of playing on the construction of masculinity in that somehow your value as a man is sort of tied into your sexual performance,” Pierson said.

That’s why critics worry that the drugs are used by some just for enhancement. Keiller agreed and runs into that problem on occasion.

“I refuse to give it to a man unless he’s willing to talk about it a little bit,” Keiller said.

But overwhelmingly, he said, the ads are bringing men to him who have overcome being embarrassed to talk about a once-taboo subject.

Erectile dysfunction (ED) is the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.¹ The prevalence of ED is estimated at 35% in men over age 60 and in some studies as high as 50%.^2,3 It has been estimated that globally, the number of patients with ED will exceed 300 million by 2025.⁴ Despite recognition that ED is a common medical illness and not only psychogenic in origin–as historically described–patients and physicians alike often have difficulty communicating on this topic. In an international survey of more than 27,000 men and women, only 9% of respondents reported that their physician had inquired about their sexual health in the last three years.⁵

Pharmacists–a trusted source of objective medical information–are responsible for counseling and routinely dispensing medications for ED. This affords many opportunities to improve outcomes as well as provide valuable education on optimization of treatments–especially when a suboptimal response is experienced with phosphodiesterase type 5 (PDE-5) inhibitors. ED is an important patient care topic, as patients may associate sexual health with vitality and overall well-being. Furthermore, there are several treatment options, making this an amenable medical condition potentially responsive to both pharmacotherapy and nonpharmacologic measures.

Etiology of Erectile Dysfunction
A complex sequence of biochemical steps results in an erection during sexual stimulation.⁶ The principal mediator is nitric oxide (NO), which activates guanylyl cyclase, thereby increasing concentrations of cyclic guanosine monophosphate. The resulting relaxation of smooth muscle allows for engorgement of the penis to provide rigidity for intercourse.

ED has multiple etiologies including vascular, neurologic, and endocrine disorders. This highlights the importance of a proper physical exam and a thorough patient history. Many patients have specific modifiable vascular risk factors that can impact erectile function. Patients with vascular risk factors including hypertension, coronary artery disease (CAD), high cholesterol, and diabetes are at increased risk for ED compared to patients without these conditions.^7,8 Smoking appears to further increase the risk of ED in patients with vascular risk factors, likely due to direct effects on endothelial function.⁹ Health care providers should routinely remind current smokers with ED of the beneficial effects of smoking cessation from both a cardiovascular and sexual health perspective. In regard to diabetes, poor glycemic control and duration of disease further increases risk, which highlights the need for prevention and vigilance in this patient population.¹⁰

Obese patients are also at risk for ED, possibly due to increases in oxidative stress that may render NO inactive.¹¹ In obese men, lifestyle changes including moderate weight loss and increased exercise can have a significant impact on retaining and improving erectile function. Additionally, ED is often the first sign of underlying, undiagnosed cardiovascular disease.¹¹

It is important that pharmacists recognize medication classes associated with ED and sexual dysfunction. For example, incidence of selective serotonin reuptake inhibitor (SSRI)–induced sexual dysfunction is estimated at 30% to 50%.¹² In this situation, as well as in beta-blocker–induced ED, drug holidays to avoid sexual side effects should not be routinely recommended. Whenever possible, conversion to another agent within the same therapeutic class with a lower incidence of sexual side effects should be recommended. PDE-5 inhibitors may be appropriate and have been studied to improve specific causes of drug-induced sexual dysfunction.^13,14 Other medications commonly associated with ED include antihypertensive agents such as calcium channel blockers, beta-blockers, and thiazide diuretics as well as miscellaneous agents including methotrexate, interferon-alpha, and 5-alpha reductase inhibitors.¹⁵

Phosphodiesterase Inhibitors
When potentially reversible causes of ED have been ruled out, PDE-5 inhibitors are considered first-line therapy unless otherwise contraindicated by patient-specific comorbidities or concomitant administration with certain medications.¹⁶ Three agents are currently available: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Current guidelines for the management of ED do not favor one agent over another for initial treatment of ED. Post-hoc analysis of phosphodiesterase inhibitor– naГЇve men did not identify specific patient characteristics predicting patient preference for either sildenafil or tadalafil.¹⁷ Specific differences between the three available agents are largely based on pharmacokinetics and onset of action (Table 1).^18-20

Patients with CAD who are considered for PDE-5 inhibitor therapy should undergo cardiovascular risk stratification.^21,22 Patients determined to be at low risk may receive medication for ED and may cautiously resume sexual activity. Higher-risk patients, including those with unstable angina; untreated, poorly controlled, accelerated, or malignant hypertension; a recent (within two weeks) myocardial infarction (MI); or aortic stenosis should be advised to abstain from sexual activity until stabilization has occurred.²² Due to possible precipitous decreases in blood pressure, PDE-5 inhibitors should not be used in men taking nitrates.

An additional contraindication to PDE-5 inhibitor use is prior diagnosis of nonarteritic ischemic optic neuropathy (NAION), a rare ophthalmologic disorder. Temporal association between PDE-5 inhibitor use and diagnosis of NAION has been documented; however, a cause-effect relationship has yet to be fully established.²³ Patients with this ophthalmologic disorder often share similar vascular risk factors including hypertension and smoking–further confounding this relationship. A case control study examining this issue found no increased risk of this condition except in patients with a history of MI.²⁴ Overall, the risk of this condition is low, but patients with a history of NAION should not take PDE-5 inhibitors.

Other rare side effects reported with tadalafil and sildenafil include sudden loss of hearing; however, a cause-effect relationship has yet to be fully established.^19,25 More commonly reported side effects include changes in blue-green vision with sildenafil and a higher reported incidence of back pain with tadalafil.^18,19

While PDE-5 inhibitors have revolutionized the management of ED, the remainder of this review will focus on alternative treatment options and potential treatment strategies in the setting of failed PDE-5 inhibitor therapy or contraindications.

Alternative Therapies
Approximately one in three men who suffer from ED will have inadequate response, contraindications, or side effects to PDE-5 inhibitors.¹⁵ The American Urological Association (AUA) states that for patients who fail an adequate trial of a PDE-5 inhibitor, a trial of another such agent may be appropriate. However, no studies have shown benefit for one PDE-5 inhibitor over another.¹⁶ Alternative therapies include intracavernosal injections, intraurethral therapy, vacuum devices, and penile prostheses (Table 2). Although more invasive than oral medications, these options are effective for many patients.

Injectable Therapies: One injectable medication used as a second-line therapy in the treatment of ED is alprostadil. This naturally occurring form of prostaglandin E₁ acts to increase cyclic adenosine monophosphate (cAMP), which in turn relaxes smooth muscle, leading to an erection.²⁶ Phentolamine (an alpha-adrenergic blocker) and papaverine (a nonspecific phosphodiesterase inhibitor) both act as vasodilators and may be used in combination with alprostadil if the patient has an inadequate response to alprostadil alone. Alprostadil is the most effective monotherapy followed by papaverine; phentolamine is used only in combination as augmentation. It may be preferable to use all three medications in combination, as efficacy increases from approximately 80% to 92% with use of the combination (tri-mix), and side effects may decrease since lower doses of each agent are used.^15,27 When side effects do occur, they may include penile ache (5%) and, in rare cases, penile fibrosis or priapism.¹⁵ Hypotension is also rare.²⁶

Although intracavernosal injection provides local, rapid response, the invasiveness and requirement for injection may deter patients or decrease compliance.²⁸ As previously noted, injection therapies are considered second-line treatment and are typically offered to patients who have failed or cannot tolerate therapy with PDE-5 inhibitors. Contraindications to intracavernosal injection therapy include anatomical deformation of the penis, leukemia, myeloma, sickle cell disease, predisposition to priapism, or hypersensitivity to the agents.²⁶ Precautions to their use include bleeding disorders or concomitant use of anticoagulants.²⁶ When this therapy is initiated, the first dose should be administered under the supervision of a health care provider to allow teaching of administration technique and titration of dose required to obtain adequate erection.

Intraurethral Suppository: Alprostadil may also be administered via urethral suppository. A medicated pellet more commonly called MUSE (medicated urethral system for erection) is inserted by the patient into the distal urethra prior to intercourse. This formulation often provides local, rapid response although efficacy (~67%) may be less than intracavernosal injection.²⁹ Despite using the same active medication to achieve an erection, it has been shown that patients who fail intracavernosal injection therapy may have success with use of intraurethral alprostadil.²⁹ Engel and McVary reported in a retrospective review that 58% of men who described intracavernosal injection as “not effective” were able to achieve an erection with use of intraurethral alprostadil in the clinic setting.²⁹ It is recommended that intraurethral suppository be offered to patients who have failed PDE-5 inhibitors.¹⁵ It may be an especially useful second-line option for patients who are deterred by intracavernosal injections due to needle aversion or pain from injection. Side effects are similar to those of intracavernosal injection and include local pain (32%) and, in rare cases, persistent penile pain or priapism.³⁰ Intraurethral administration may also lead to urethral bleeding (5%) and increased risk of urinary tract infection (0.2%).²⁷

Vacuum Constriction Devices: Other second-line therapies include vacuum constriction devices (VCDs), which use negative pressure to draw blood into the penis. A band is placed at the base of the penis to maintain the erection for no longer than 30 minutes. Efficacy of VCDs is unclear due to the lack of high-quality studies, but it has been estimated at 35% to 90%.^15,27 Low patient acceptability again limits the use of these devices, but they may be appropriate and effective, especially when it is necessary to avoid drug therapy and provide a noninvasive mode of administration. Use of anticoagulants or presence of a bleeding disorder are considered contraindications to use of VCDs.²⁷

Penile Prostheses: Penile prostheses are considered third-line treatment options due to the need for surgical implantation of the devices. There are two main types–malleable, also known as semirigid, and inflatable devices. Despite their invasiveness, prostheses may be preferred by patients over vacuum devices. Recent analysis of patient satisfaction and device reliability have yielded very positive results.^15,31 Essentially all patients with proper device function can achieve an erection. Failure of the device most often results from infection or mechanical failure. The five-year rate of mechanical failure is estimated to be 6% to 16% depending on the type of device used.¹⁶ Infection can also lead to prosthesis failure, but with appropriate surgical techniques and antibiotic practices these rates are only 2% to 3% (slightly higher in diabetics).²⁷ Device manufacturers have also attempted to decrease rates of infection by use of antibacterial-impregnated prostheses or hydrophilic coatings.^16,27 If infection does occur, the prosthesis must be removed and infection treated appropriately. Reimplantation is an option after a period of several months, but is more technically challenging. Due to the replacement of penile erectile tissue during implantation, PDE-5 inhibitors, intracavernosal injection, and MUSE are not considered options after implantation and subsequent removal of a prosthesis. In these patients, the only viable option remains reimplantation. However, a vast majority of patients have previously failed most other therapies upon arrival to this stage.

Other Alternative Therapies: Despite being advertised as an herbal alternative for the treatment of ED, yohimbine is not recommended by the AUA, as safety and efficacy in humans have yet to be determined. This herbal medication, believed to increase libido in rats, has alpha₂-adrenergic inhibition leading to increased blood pressure, heart rate, and motor activity in humans.¹⁶ Yohimbine may also cause irritability and tremor.¹⁶

Use of trazodone for treatment of ED is not recommended by the AUA. It has been hypothesized that this antidepressant, via antagonism of alpha₂-adrenergic receptors, would possibly relax penile smooth muscle and dilate penile arteries, leading to an erection. Results from clinical trials have been conflicting and, therefore, its use cannot be recommended.¹⁶

It is estimated that approximately 12% of patients with ED have hypogonadism, and in some cases this may be a reversible cause of ED through treatment with administration of exogenous testosterone.³² If symptoms persist beyond three months of testosterone therapy, dysfunction is most commonly due to or complicated by the adverse effects of the patient’s comorbid conditions, including impaired penile vasculature.³² Dual treatment with testosterone and a PDE-5 inhibitor may be indicated. As AUA guidelines state, administration of exogenous testosterone in someone with normal serum testosterone values is not recommended.¹⁶

Subgroup Analysis: Status Post Radical Prostatectomy
As practitioners attempt to individualize treatment of ED, unique situations arise. A common scenario includes treatment of ED post radical retropubic prostatectomy (RRP), as with the 50-year-old man presented in the case study. Prostate cancer is the fourth most common cancer in adults, and it is estimated that approximately 40% of patients with localized disease will undergo radical prostatectomy.³³ Urinary incontinence and ED are the most common complications from this procedure, with the latter attributed mainly to damage to nerves regulating erections.³³ Advances in surgical techniques, including nerve-sparing procedures, may reduce ED and subsequently improve response to PDE-5 inhibitors.

Therapy with PDE-5 inhibitors may be warranted not only to treat but also to prevent ED in patients who have undergone RRP. Bannowsky et al conducted a randomized, placebo-controlled trial (N = 43) comparing sildenafil 25 mg nightly on recovery of erectile function after nerve-sparing radical prostatectomy (NSRP).³⁴ Their findings suggest that sildenafil may enhance recovery of erectile function by supporting cavernosal oxygenation and preventing subsequent fibrosis. One year postsurgery, 47% of patients randomized to sildenafil were able to achieve and maintain an erection sufficient for vaginal intercourse, compared to 28% of controls. When “on-demand” sildenafil 50 to 100 mg as needed was allowed, potency increased to 86% versus 66%, respectively (P <.001).³⁴

Based on these findings, Bannowsky et al have proposed a new therapeutic concept, termed the Kiel concept, for optimum reestablishment of erectile function and satisfying sexual function after NSRP, which is based on the significant benefit observed in patients taking sildenafil 25 mg nightly.³⁴ They suggest that patients with no confirmed erections at one year postsurgery should undergo a trial of intracavernosal injection therapy, and if no spontaneous erections occur at two years, more invasive therapy may be required.³⁴ Future studies are needed to further investigate the theories behind the Kiel concept, as it remains controversial; however, this study conveys the possible importance of early therapy to support cavernosal oxygenation after RRP. It also emphasizes the importance of following up with patients for symptoms of ED and utilization of alternative therapies to treat this clinical problem.

Conclusion
In summary, pharmacists should be readily available to counsel patients on the differences not only between PDE-5 inhibitors but between second-line therapies as well. Because failure of one PDE-5 inhibitor does not necessarily preclude effectiveness of another agent, pharmacists should determine if the medication has benefited the patient. In the setting of failed PDE-5 inhibitors, several alternative therapies exist, and patients may be considered for second-line treatment options. Patient specific factors, as well as convenience and patient adherence, should be considered prior to initiating therapy with any agent.

With the number of visitors to Internet drug outlets nearly tripling in the last year, the risk to patients’ health is higher than ever. Based on its assessment of more than 1,000 Internet drug outlets selling medicine online, the National Association of Boards of Pharmacy(R) (NABP(R)) finds that 97% of these sites appear to be operating out of compliance with state and federal laws or established patient safety and pharmacy practice standards. Most of these sites appear to violate several criteria for legitimate pharmacy practice. For instance, 93% do not require a valid prescription, 25% do not secure patients’ personal information, and 61% offer foreign drugs, which are not approved by the US Food and Drug Administration (FDA), and which, according to federal law, are not legal to sell in the US.

“NABP understands the need for many patients to consider cost in regard to their prescription medications,” says NABP President Rich Palombo, RPh. “Our hope, however, is that no one should have to sacrifice safety in the interest of saving money.”

NABP historically has viewed the use of medications obtained from foreign sources cautiously for two reasons: (1) federal law prohibits it, and (2) proponents have yet to develop provisions to ensure patients receive safe, effective medications. Currently, no safeguards exist to protect shipments of foreign medications entering the US from infiltration by counterfeit and substandard drugs. Until such provisions are in place, use of foreign medicines will present a risk.

Foreign medicines are often purchased from Internet drug outlets, the majority of which have been found to be operating outside of the regulatory framework established to protect patient health. “Buying drugs online continues to be fraught with fraudsters,” MarkMonitor reports in its summer 2008 Brandjacking Index(TM). In its survey of nearly 3,000 Internet drug outlets, MarkMonitor “found numerous examples of con artists who hijack well-known brands for their own profit and continue to thrive by selling illicit drugs, endangering consumers’ health and well-being.” Meanwhile, the number of visits to Internet drug outlets continues to rise. The report cites 99,000 visitors to Internet drug outlets by the second quarter of 2008, compared to 32,000 visitors by the same time last year.

Depending on the country of origin, the likelihood of foreign medications being counterfeit may be significant. The World Health Organization estimates that counterfeit drugs range from less than 1% in developed countries to more than 30% in some developing countries. Drug counterfeiting occurs less frequently in the US than in other countries due to the strict regulatory framework that governs the production of drug products and the distribution chain, and enforcement against violators.

Web sites that sell medicine over the Internet may not be legitimately licensed pharmacies in any country, or they may dispense medicine obtained from anywhere in the world. When patients do choose to purchase medicine over the Internet, FDA advises them to use Internet pharmacies that are accredited through the Verified Internet Pharmacy Practice Sites(TM) (VIPPS(R)) program. These sites, displaying the VIPPS seal of approval, have undergone and successfully completed the rigorous NABP accreditation process, which includes a thorough review of all policies and procedures regarding the practice of pharmacy and dispensing of medicine over the Internet, as well as an on-site inspection of facilities used by the site to receive, review, and dispense medicine. Unless medications have been purchased from a state-licensed Internet pharmacy in the US, the safety and efficacy of these medications cannot be guaranteed.

To educate and empower patients to make informed decisions when buying medicine online, NABP monitors Web sites that sell prescription medicine and distinguishes those sites that do, and do not, appear to comply with state and federal laws and established patient safety and pharmacy practice standards. As of October 2008, NABP has assessed more than 1,000 Internet drug outlets, 999 of which appear to be operating in conflict with pharmacy laws and standards and have been named as Not Recommended on the NABP Web site, www.nabp.net/ip.asp. MarkMonitor states in its Brandjacking Index, “we strongly urge consumers to check this listing before they purchase any medications online.”