The Dangers Of Pharmacy Compounding—3 Dead, 13 Hospitalized From Bacterially Contaminated Injections

Betamethasone injection (CELESTONE SOLUSPAN), a cortisone type anti-inflammatory drug, produced or compounded at Doc’s Pharmacy in Walnut Creek, California from non-sterile powder, has been linked to death and serious illness. Of 38 persons known to have received the drug, 13 were hospitalized. Of these, five later contracted meningitis, three of whom died.

The betamethasone apparently became contaminated with Serratia bacteria when 300 milliliters of the drug (about a third of a quart) was being transferred into 5 milliliter (a teaspoonful) vials before sale to an area surgical center.

Serratia bacteria usually causes illness only in patients with compromised immune systems or those who are very sick and confined to a hospital intensive care unit (ICU). Meningitis is an inflammation of the lining of the brain and spinal cord that can be caused by bacteria, viruses, or chemicals. The cases of meningitis may have resulted from the contaminated drug being injected into the spines of these patients. At least one of the patients who died, a 47-year-old man, was being treated with the betameth-asone injection for chronic lower back pain. Serratia meningitis is not a contagious form of the disease.

We wrote about the dangers of pharmacy compounding in the November 1998 issue of Worst Pills, Best Pills News. Provisions in the Food and Drug Administration Modernization Act (FDAMA) of 1997 were used as cover by compounding pharmacists to engage in the small scale manufacture of prescription drugs under the pretense of traditional pharmacy compounding. There are some legitimate medical reasons for compounding drugs but they are extremely limited and the need for compounded sterile products made from non-sterile bulk drug substances is even rarer.

The FDA oversees the manufacture of prescription drugs under regulations known as Good Manufacturing Practice (GMP) guidelines. These are meant to ensure the quality and stability of finished products so that patients and physicians can be assured of the same therapeutic effect from different batches of a particular drug. GMP guidelines also ensure that drugs intended for intravenous (IV) or other types of injection are sterile. There is a “zero-tolerance” standard for the regulated producers of prescription drugs for even a single bacterium in a product that is intended for injection into a patient.

Compounding pharmacists, on the other hand, manufacture drugs without having to prove that their products are safe and effective or that they are produced in facilities meeting GMP guidelines. There was no regulatory body, either state or federal, that required Doc’s Pharmacy to sell sterile injectables, and this holds true nationwide.

On February 6, 2001, the Ninth Circuit Court of Appeals struck down the pharmacy compounding provisions of FDAMA on First Amendment grounds as a result of litigation brought by a group of compounding pharmacists that sell their unregulated products through the mail throughout the U.S. FDAMA had prohibited compounding pharmacists from advertising that they produced specific products (such as compounded natural hormone replacement therapy) and could only advertise that they specialized in compounding.

The FDA could revert to the stronger, pre-FDAMA law and regulate compounded drugs as unapproved new drugs. However, the agency has chosen not to do so at this time, perhaps because of its limited resources and fear of the compounding pharmacies’ collective political clout. State boards of pharmacy in many cases are strapped for staff and resources and there are no state regulations that require pharmacy-compounded drugs to be safe and effective or produced in facilities meeting GMPs. This exposes the public to a dangerous marketplace where untested prescription drugs can be sold. A rule that was current in Imperial Rome still applies in the third millennium A.D: Caveat emptor (let the buyer beware).

There are other aspects of the Doc’s Pharmacy case that are troubling from a patient safety perspective. A comprehensive review of the injection of steroids such as betamethasone into the spine, published in the April 2001 issue of The Journal of Neurology, Neurosurgery and Psychiatry, found the practice questionable. The authors of the review concluded:

• Intraspinal steroid therapy is not effective therapy for back pain or radicular syndromes [pain from nerve roots] because steroid formulation, placebos, and sham injections have similar outcomes.
• Patients should be informed that there is no evidence that epidural steroid injections provide permanent relief of pain. Serious permanent complications to the spinal cord, nerve roots, or peripheral nerves are a rare but certain risk.

A tainted, unapproved pharmacy-compounded drug from Doc’s Pharmacy that may have been given for an inappropriate purpose may have needlessly injured and killed the patients in Walnut Creek.

Compounding pharmacists are also known for outright quackery, usually in conjunction with complementary-alternative-medicine physicians as remedies for their sagging profits. In the March 2000 issue of Worst Pills, Best Pills News we wrote about Scarborough Pharmacy in Findlay, Ohio promoting a compounded timed release thyroid hormone treatment for a non-existent disorder named “Wilson’s Syndrome” after its inventor. This pharmacist was finally disciplined by the Ohio Board of Pharmacy, but only received a slap on the wrist for his Wilson’s Syndrome escapade and other dangerous practices. Just recently three patients were hospitalized in Atlanta from a compounded drug that contained too much thyroid hormone prescribed for Wilson’s Syndrome.

A popular profit center for the nefarious duo of compounding pharmacists and complementary-alternative-medicine purveyors is the promotion on the Internet of “risk free” compounded natural hormone replacement to women. We warned of the dangers of this practice in the February 2001 issue of Worst Pills, Best Pills News.

Doc’s Pharmacy is also into pushing herbs in addition to natural hormone replacement therapy. According to its web site, which we accessed on July 2, 2001, “Doc” advertises “a Certified Herbalist on staff who works with patients through individual consultation creating specific formulas to enhance wellness” and that Doc’s has “the ability to compound specific nutritional formulas based on your needs.” Boards of pharmacy should consider regulations to protect the public against pharmaceutical quackery.

The International Academy of Compounding Pharmacists, a trade organization that claims a membership of about 1,300, has maintained before the FDA that because there are no reports of harm from pharmacy-compounded substances this is proof of their safety. Such a statement is totally misleading, as this organization knows. Pharmacists know, or should know, that there is no system in place to accurately identify patients killed or injured by prescription drugs. In fact, compounding pharmacists are not even required to report any problems with their products to either state or federal authorities. The owner of Doc’s Pharmacy is a director of this organization.

It was not a matter of if, but of when, a large enough group of patients would be injured or killed for the public to take notice. In the wake of the Doc’s Pharmacy tragedy, the San Francisco Chronicle wrote a scathing editorial about the inadequate and dangerous lack of oversight of compounding pharmacies in California stating

The recent deaths and disease resulting from a contaminated batch of pharmacy medicine should be a jarring warning to public health officials. Either step up oversight and regulation of pharmacies or swallow hard and brace for an even more devastating catastrophe.....While we should consider ourselves lucky, the Board of Pharmacy should quickly heed the alarm. It should stage unannounced pharmacy inspections to curb chances for a major medical mishap and restore public faith in the process.

A California state legislator has indicated his intention to introduce legislation that would distinguish legitimate compounding from the type of small volume manufacturing that was taking place at Doc’s Pharmacy. Other states must heed the Doc’s Pharmacy warning as the essentially unregulated manufacture of prescription drugs takes place all across the country and we have no indication that the FDA will step in any time soon.

What You Can Do

You should be very skeptical of pharmacies promoting compounded drugs. If a pharmacist or a physician tell you that the only treatment for your condition is with a compounded drug, get a second opinion.