News You Shouldn't Miss -- The Wall Street Journal

CDC Says a Number of Drugs Besides Cipro Work on Anthrax

Surge in Use of Cipro Spurs Concerns About Side Effects

Bayer's Cipro Will Be Profitable, Even on Discount Deal With U.S.

Online Cipro Supplier Is at Center of Storm As Demand Brings Both Sales and Scrutiny

Special Report: Aftermath of Terror

CDC Says a Number of Drugs Besides Cipro Work on Anthrax

By SCOTT HENSLEY and ANTONIO REGALADO
Staff Reporters of THE WALL STREET JOURNAL
 

With a nationwide rush on the antianthrax drug Cipro straining supplies in drug stores and hospitals, public-health authorities are reminding doctors that doxycycline, a generic drug, is believed to be just as effective as a foundation for anthrax treatment and as a protective agent after suspected inhalation of anthrax spores.

Guidelines released by the Centers for Disease Control and Prevention in Atlanta advise doctors to treat patients who have diagnosed anthrax infections first with intravenous Cipro or doxycycline, plus at least one other antibiotic to increase the odds of killing the bacteria. The patient eventually can be switched to oral therapy of 500 milligrams of Cipro, or ciprofloxacin, twice a day, or 100 milligrams of doxycycline twice a day.

So far, the CDC has tested 11 anthrax samples isolated from victims of the attack or contaminated workplaces for susceptibility to about a dozen different antibiotics, including Bayer AG's Cipro, penicillin, rifampin and vancomycin. Nearly all the drugs were effective in killing anthrax bacteria in test-tube experiments. Only one major class of microbe-fighter, called cephalosporins, didn't perform as well against the anthrax, suggesting the strain may have a natural immunity to this class of drugs. Because a particular kind of resistance may occur, the CDC also cautioned against using penicillin alone to treat anthrax infections.

However, the CDC told doctors who are prescribing an antibiotic as prophylaxis after suspected inhalation of spores that penicillin is thought to be acceptable in cases where Cipro may cause harmful side effects. All the antibiotics recommended have side effects that range from allergic reactions to diarrhea.

"From the publicly available information, these [anthrax cases] are very susceptible to a broader range of antimicrobials than Cipro or just the quinolones," the class of drug that includes Cipro, said P.J. Brennan, an infectious disease specialist at the University of Pennsylvania Health System in Philadelphia. So long as the anthrax bacterium hasn't been engineered to be resistant to these medicines, any of them could provide effective treatment, he said. "The recommendation for Cipro," he explained, "is based on the assumption that any terrorist worth his salt would try to engineer bacteria resistant" to older drugs.

Anthrax spores are hardy and resist destruction. Even the strongest antibiotics don't appear effective in killing them, experts say. Instead, the drugs halt the development of the disease after inhalation by hitting the bacteria as they emerge from the spore form. To work best, the antibiotics need to be circulating in the bloodstream for as long as significant numbers of spores might be present in the lungs, or elsewhere in the body. Therefore, a 60-day course of antibiotic treatment is recommended to treat or prevent anthrax infection after suspected exposure to spores.

There are no well-controlled studies in humans of antibiotics to treat inhaled anthrax. Even anecdotal reports of treatment are sparse because the disease has been so rare. During the Gulf War, however, researchers at the U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Md., tested the effectiveness of various antibiotics in rhesus monkeys to prevent the development of anthrax after inhalation of spores. Cipro, penicillin and doxycycline were all effective against the inhaled form of the disease.Meanwhile, GlaxoSmithKline PLC is working with the U.S. government to receive expedited review for two of its antibiotics -- Amoxil and Augmentin -- to be used for the treatment of anthrax.

The pharmaceuticals company said if current testing shows efficacy against anthrax, and the FDA approves the use of one or both of the antibiotics, GlaxoSmithKline of the United Kingdom expects to provide the drugs free to the government for use in treatment of anthrax.

"GlaxoSmithKline is confident the company has adequate manufacturing capability to meet potential need," the company said in a statement.

Write to Scott Hensley at scott.hensley@wsj.com¹ and Antonio Regalado at antonio.regalado@wsj.com²

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Health Journal

Surge in Use of Cipro Spurs Concerns About Side Effects

By TARA PARKER-POPE
Staff Reporter of THE WALL STREET JOURNAL
 

AFTER ANTHRAX FEARS spurred everyone from New York's governor to hundreds of postal workers to take the antibiotic Cipro, drug-safety experts are now predicting a rash of health problems caused by the drug itself.

Most troubling is the fact that three similar drugs, all chemical cousins of Cipro, already have been pulled off the market after being linked with severe side effects and even death.

Cipro, or ciprofloxacin, is one of several fluoroquinolones, a controversial class of antibiotics that can cause a range of bizarre side effects: from psychological problems and seizures to ruptured Achilles tendons. Fluoroquinolones made by other manufacturers, such as Johnson & Johnson's Levaquin, also are being considered for use in treating anthrax exposure.

Cipro is generally regarded as safe, but concerns are growing as its use surges amidst the anthrax scare. And some of the potential side effects of fluoroquinolones, such as cardiovascular complications, simply haven't been widely studied."

"I'm very concerned. There are safer drugs that are available for this, and they're not being used," says Raymond Woosley, vice president, health science, University of Arizona in Tuscon.

Bayer declined to comment on questions about Cipro side effects.

AT TABLOID PUBLISHER American Media, where the first case of anthrax was diagnosed and many workers are taking Cipro, some have complained of stomach upset or feeling "spacey" since taking the drug. One employee had a severe allergic reaction and another suffered a seizure; both were hospitalized, according to an AMI employee who asked not to be named. Some workers there, after researching side effects, have asked to switch to other antibiotics.

When first introduced 15 years ago, fluoroquinolones were celebrated as effective bacteria fighters without the resistance issues that sometimes render more traditional antibiotics ineffective. As use has grown, resistant strains have emerged, but the drugs remain some of the most heavily prescribed antibiotics.

But in 1992 Abbott Laboratories' temafloxacin, marketed as Omniflox, was withdrawn after only three months following 50 severe cases of adverse reaction, including three deaths. In 1999, 14 cases of acute liver failure, including five deaths, were linked to Pfizer's drug trovafloxacin, marketed as Trovan, prompting the FDA to severely limit its use. Later that year, Glaxo Wellcome's grepafloxacin, marketed as Raxar, was withdrawn after reports of heart rhythm abnormalities, with seven deaths.

Fluoroquinolone users who have suffered severe side effects call themselves "floxies" and have created their own Web site (www.geocities.com/quinolones¹). The Annals of Pharmacotherapy published a review of 45 cases of severe adverse effects from quinolones, including 11 cases involving Cipro. The Philadelphia law firm Sheller Ludwig Badey has been involved in about two dozen cases of severe quinolone side effects.

Doctors say that, in general, fluoroquinolones don't carry any higher rate of side effects than traditional antibiotics. But the nature of the side effects of fluoroquinolones often are so strange, patients often don't associate them with the drug.

DAVID A. FLOCKHART, professor of medicine and chief of clinical pharmacology at Indiana University School of Medicine, says as many as a third of patients taking a fluoroquinolone will experience some sort of psychiatric side effect, such as anxiety, personality change or confusion. "The psychiatric effects of the fluoroquinolones are underappreciated by the medical profession as well as by the public," says Dr. Flockhart, who has treated more than 100 patients with severe psychiatric side effects.

Dr. Flockhart says the drugs are useful in treating infection because they quickly reach high concentrations in the blood. That means the drugs can quickly concentrate in the brain and interfere with a receptor that normally prevents seizures.

After taking a single dose of Johnson & Johnson's Floxin for a mild urinary tract infection, 36-year-old Diane Ayres suffered a severe manic reaction with confusion, vision problems and insomnia. Doctors blamed the Floxin, and the episode left her with manic-depressive illness. "These are drugs that should be reserved primarily in situations where another drug has failed," says her husband, Stephen Fried, who has written a book, "Bitter Pills: Inside the Hazardous World of Legal Drugs."

Fluoroquinolones also are known to trigger another bizarre side effect -- tendon rupture, particularly the Achilles. Kansas dermatologist J. Michael Casparian took Cipro five years ago for a cough. Six months later he was playing charades in his living room when he experienced what felt like "a baseball bat hitting my ankle." A few years later, his other Achilles tendon snapped.

It's unclear why some people react to fluoroquinolones while others do not. Someone with an existing psychiatric condition, seizure disorder or with a history of head trauma shouldn't take fluoroquinolones. In addition, a patient who is prescribed a fluoroquinolone should ask whether another antibiotic, particularly one they've used before without ill effect, couldn't be used instead.

E-mail comments to healthjournal@wsj.com²

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Special Report: Aftermath of Terror

Bayer's Cipro Will Be Profitable, Even on Discount Deal With U.S.

By GARDINER HARRIS
Staff Reporter of THE WALL STREET JOURNAL
 

Under pressure from the U.S. government to lower its prices, Bayer Corp. announced what it termed a "historic" agreement Wednesday to sell Cipro, the anthrax-fighting antibiotic, for 95 cents a pill to the government. But generic makers and critics say Bayer's new pact is still enormously profitable.

Ranbaxy Inc., a generic-drug maker in Princeton, N.J., has offered to sell the pill for 40 cents apiece in the U.S., "and we'd still be making money at that price," said Dipack Chattaraj, Ranbaxy's president.

Ranbaxy's parent company is based in India and sells a generic form of Cipro there for about 30 cents a pill. Some competitors in India sell it for about 10 cents a pill. "It's a very easy product to make," Mr. Chattaraj said. "So when generic makers come on the market, the price will drop very fast."

Two other U.S. generic-drug makers who didn't wish to be identified said they could sell the pill for 40 cents in the U.S. and turn a profit. In fact, some international drug-distribution companies offer to sell the drug for as little as a nickel a pill.

"This company is profiteering in a time of national emergency," said James Love, a consumer activist and frequent gadfly to drug companies.

A Bayer spokeswoman refused to answer questions about the company's cost and profits surrounding Cipro.

Cipro's average wholesale price in the U.S. is about $4.67 per pill. The company normally sells the pill to the U.S. government for $1.77 per pill. Health and Human Services Secretary Tommy Thompson threatened to break Cipro's patent and order the pill from generic-drug makers unless Bayer lowered the price further. Bayer then announced it would sell the pill to the government for 95 cents apiece for the first 100 million pills, 85 cents each for the second 100 million pills and 75 cents each for the third 100 million.

"Bayer is fully committed to supporting America in its war on bioterrorism," said Helge Wehmeier, president and CEO of Bayer Corp., the U.S. subsidiary of Germany's Bayer AG, in a statement released Wednesday. "The men and women of Bayer are 100% committed to delivering this vital antibiotic to the U.S. government on schedule."

Mr. Thompson has proposed buying nearly 300 million pills of Cipro as part of the national pharmaceuticals stockpile, a cache of medicine used only in emergencies. So the pills the government is buying will not interfere with Bayer's usual selling market.

Mr. Thompson's threat to defy Bayer's patent unless the company lowered its price sent a chill through the entire pharmaceuticals industry. The drug industry has for years been fighting efforts by activists and poor nations to make such seizures easier in large-scale emergencies, such as the AIDS pandemic in Africa. The industry's staunchest ally to date in this fight has been the U.S. government.

So the industry has been trying to show it is pitching in to help the nation cope with bioterrorism. Several large pharmaceuticals companies are proposing to supply smallpox vaccines. Others are offering to show their own antibiotics fight anthrax.

"Putting aside personal and company considerations in a time of crisis is a tradition we honor, and we think our companies are committed to that," said Jeff Trewhitt, a spokesman for the Pharmaceutical Research and Manufacturers of America. Asked whether profit was among things the companies would put aside, Mr. Trewhitt replied, "It means making some compromises."

Some activists insist the government should respond to Bayer's price by seizing its patent and ordering supplies from generic-drug makers. Government leaders "are making it clear that they cannot stand up to pharmaceutical companies," said Tim Fuller, executive director of the Gray Panthers, a consumer group.

Bayer needs all the Cipro sales it can get. The company was forced this summer to withdraw its biggest-selling drug, anti-cholesterol pill Baycol, after deaths among some users. Cipro is now the company's sole big seller. "This is simple," said Neil Sweig, an analyst for Ryan, Beck & Co. "They've got a patent and they're saying, 'You want my product? Make it worth my while.' "

Cipro's patent doesn't expire until December 2003, at which time generic forms would be allowed on the market.

Also Thursday, lawyers for the Prescription Access Litigation Project announced a suit against Bayer to overturn a 1997 agreement between Bayer and Barr Laboratories Inc. in which Bayer pays Barr as much as $30 million a year until 2003. The agreement settled a lawsuit in which Barr charged that Cipro's patent was invalid.

William Haddad, chairman and chief executive of generic-drug maker United States Research and Development Corp., estimated that Bayer spends no more than 20 cents to make a Cipro pill. "Everybody else is making a sacrifice in these times," said Mr. Haddad. But Bayer "is still making an extraordinary profit when selling to the federal government. They are not doing it out of their heart."

Write to Gardiner Harris at gardiner.harris@wsj.com¹

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E-Business

Online Cipro Supplier Is at Center of Storm As Demand Brings Both Sales and Scrutiny

By JULIA ANGWIN
Staff Reporter of THE WALL STREET JOURNAL
 

MORRISVILLE, N.C. -- If you buy Cipro online these days, it's likely to come from a low-slung brick building in an office park in this Raleigh suburb.

The half-empty, unpainted offices are home to MedicalWeb.com Inc., an Internet operation whose fortunes are suddenly booming from the recent spike in demand for ciprofloxacin, an antibiotic used to treat anthrax exposure. Other antibiotics can also be used to treat anthrax but Cipro is the only one that has won specific approval from the FDA for anthrax treatment.

Of the approximately 30 Web sites advertising Cipro sales, at least eight connect purchasers to MedicalWeb.com (www.medicalweb.com¹). A company subsidiary, VirtualMedicalGroup.com (www.virtualmedicalgroup.com²), hooks patients up with doctors, who write online prescriptions for various ailments. The drugs are shipped by another subsidiary, 1stOnlinePharmacy.com (www.1stonlinepharmacy.com³), to the patient. The Web sites pay MedicalWeb.com a fee for its services.

Work at the North Carolina company has been nonstop since the anthrax crisis began in early October. Employees, fueled by potato chips, are staying up late into the night to answer hundreds of calls and e-mails from patients trying to order Cipro. Before last month, the company was filling six to 10 orders for Cipro per month. Now it is more than 100 per day.

But along with sales, the Cipro boom is drawing controversy to this obscure Internet operation. Last week, the North Carolina Medical Board showed up at the offices here demanding documents for an investigation. A person familiar with the situation says the board is gearing up to take more action against the Web venture soon.

All this has Tania Malik, chief executive of all three operations, worried. "It's almost, 'Be careful what you wish for,' " she says. "We did want people to know about VirtualMedicalGroup, but my fear is people see the press and think we're arrogant."

The issue with VirtualMedicalGroup -- and other online operations like it -- is its reliance on prescriptions from doctors who have never physically met the patients for whom they are prescribing medicine. Ms. Malik says the company has a network of 35 board-certified doctors who write prescriptions for customers with whom they interact online.

"We only do conditions that we feel are appropriately treated over the Internet," Ms. Malik says. Until recently, most of those prescriptions were for the impotence drug Viagra. Now, most of them are for Cipro.

Although some medical experts say that an online interaction isn't adequate to write a prescription, it isn't illegal in most states. Some state medical boards oppose the practice -- including the North Carolina board, which describes it as "inappropriate and unprofessional" -- but few have taken action against the doctors involved.

One problem is the virtual nature of Internet exchanges. "What is real challenging about these sites is to know what physician is involved and where they are licensed," says Dale L. Austin, interim chief executive officer of the Federation of State Medical Boards of the United States.

The federation has been investigating online prescription sites for the past year, but the probe has gained a new urgency with the recent run on Cipro. Now, the federation is working with the Food and Drug Administration and various law-enforcement agencies to crack down on the doctors who are doling out prescriptions on these sites.

But it is tough to go after a practice that is legal in most states. Mr. Austin says they may use legal grounding based on "standards of care" or unprofessional conduct. The American Medical Association says prescriptions issued over the Internet based on a simple questionnaire "do not sufficiently meet the standards for good medical care" but that ultimately it is up to a doctor's judgment.

"I think it's a question of professionalism and standards of practice," says Timothy T. Flaherty, the AMA's chairman. "Physicians have to ask themselves if they are doing what is the best for the patient."

Russell E. Randall says he thinks he is doing the best for his patients when he prescribes drugs for them online for VirtualMedicalGroup. "I'm very insistent that we only prescribe when it's appropriate," says Dr. Randall, a 73-year-old retired physician in Woodbury, Conn.; he still has a medical license.

For example, Dr. Randall says he often turns down people who want drugs for urinary tract infections or depression because those are things that should be diagnosed in person. However, drugs to treat both illnesses are offered by 1stOnlinePharmacy.com. With Cipro, he says, he simply counsels people not to take it without a good reason, but says it is fine for consumers to keep some around in case of emergencies.

"If I were in the Capitol building or a place where the anthrax had occurred, would I love to have it in my hip pocket? Sure, I would," Dr. Randall says. "If you start taking it right away, then you are better off. Will there be misuse of it? Sure, probably."

Public-health officials are concerned that a flood of people buying Cipro unnecessarily could deplete supplies for those who need it, and potentially lead to the development of anthrax resistant to the antibiotic. VirtualMedicalGroup officials say they are being responsible by limiting customers to a seven-day supply of Cipro -- rather than the 60 days' worth believed to be needed to treat a full-blown case of anthrax. VirtualMedicalGroup buys its drugs from AmerisourceBergen Corp. of Valley Forge, Pa., a major pharmaceuticals wholesaler, and says that to date, it hasn't had any trouble getting supplies.

Ms. Malik, who manned the phones herself last week, says the interaction with physicians like Dr. Randall is what differentiates her online pharmacy from "rogue sites." Some other sites only offer a checklist of questions before writing a prescription, she says. Her site has software that allows doctors and patients to conduct a "virtual office visit," which is essentially a private online chat that costs $49, not including the price of the drugs.

But the virtual office visit can be quite short. When a reporter ordered Cipro last week, the doctor posted a note in the chat room describing the possible side effects of Cipro and reiterating that it should only be used in case of a "credible anthrax exposure." The reporter agreed and six tablets of the medicine were sent for $45, plus shipping. However, Ms. Malik says, some visits are quite long and involve lengthy questions and answers between the doctor and patient. The VirtualMedicalGroup's online questionnaire does not ask patients to specify why they want a Cipro prescription (see example¹⁰).

Ms. Malik's brother, Steve, founded the company in 1996, and in 1999 recruited his sister Tania, who is an attorney, to run MedicalWeb, which is private and has no venture-capital backing. Ms. Malik says MedicalWeb has been profitable for the past four months and has annual sales of about $1 million. It operates with a staff of just 15. Even she has a sense that the Cipro crisis could be thrusting her company's technology into the fore before society is ready. "We're paving the way," she says, "and maybe we're too early."

Write to Julia Angwin at julia.angwin@wsj.com¹¹

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(3) http://www.1stonlinepharmacy.com
(4) http://2-buy-cipro.com/
(5) http://cipro-antibiotics-anthrax-vaccines.com/
(6) http://1-cipro-4-anthrax.com/
(7) http://cipropharmacy.com/
(8) http://ciprostockpile.com/
(9) http://gas-masks-israeli-gasmasks.com/
(10) http://cipro-for-less.com/cipro.jsp
(11) mailto:julia.angwin@wsj.com
 

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