Drug News: Methylprednisolone (Depo-Medrol)
Woman Dies from Contaminated Drug
An elderly woman died during August 2002 in a Raleigh, North Carolina hospital, and two others contracted meningitis as a result of a medication infected with a type of mold called Wangiella dermatitidis.
According to the North Carolina Department of Health and Human Services, three patients in eastern North Carolina who received epidural injections of the steroid drug methylprednisolone acetate (Depo-Medrol) contracted dangerous fungal meningitis from this contaminated medication. State Health Officials estimated that up to 1,000 patients in North Carolina clinics may have been injected with the same drug. The Depo-Medrol made by a South Carolina compounding pharmacy was sent to facilities in Pinehurst, NC, Goldsboro, NC, and Jacksonville, NC. At least some of the contaminated drug originated from South Carolina Urgent Care Pharmacy in Spartanburg, South Carolina. At the time there was a national shortage of Depo-Medrol from the regular manufacturer Pharmacia & Upjohn, so Urgent Care was given an order to make a huge batch of the steroid and then shipped it to pain clinics in Virginia, Connecticut, South Carolina, Massachussetts, and North Carolina.
The dangerous practice of purchasing unregulated compounded versions of drugs is often done by pain and injection clinics when factory supplies run low. Unfortunately shutting down the facility until safe FDA regulated formulations are once again available is not in their ethics charter! (But as we know, even the factory version of Depo-Medrol can be harmful, and even lethal if injected epidurally!)
Meningitis is an infection of the lining of the brain and spinal cord. Symptoms include headache, fever, stiff neck, vomiting, and back pain. Health officials stated that patients who received spinal shots of this contaminated Depo-Medrol are most at risk for developing symptoms of meningitis.
Fatal Meningitis Linked to Epidural Steroid Injections that were Compounded by a California Pharmacy
Two people have died and a dozen have been hospitalized with meningitis contracted from an injectable corticosteroid compounded by a San Francisco-area pharmacy. At least 38 patients were injected with betamethasone (Celestone Soluspan) contaminated with Serratia marcescens, a common bacterium that should have been destroyed during the compounding process.
The patients were given betamethasone compounded by Doc's Pharmacy, in Walnut Creek, Calif., because the commercial equivalent was unavailable due to manufacturing problems at Schering-Plough. The drugmaker has halted production of Celestone (betamethasone) because of manufacturing deficiencies uncovered during an inspection by the Food & Drug Administration earlier this year.
At least 60 San Francisco-area physicians, hospitals, and clinics purchased betamethasone prepared by the pharmacy, according to the Contra Costa County Health Department. The department ordered a recall of all parenteral and ophthalmic products compounded by the pharmacy. The pharmacy has cooperated fully in the recall, said county health director Wendel Brunner, M.D.
"We are now sure the source of the S. marcescens contamination is Doc's Pharmacy," Brunner said. "We are continuing to investigate all aspects of these cases and have been able to rule out contamination at the health facilities" that administered the injections.
Health department technicians have cultured S. marcescens from at least 12 unopened vials of betamethasone prepared by Doc's. The common bacterium presents little or no threat unless injected. Both fatalities were caused by an epidural injection. At deadline, at least four other patients were being treated for Serratia meningitis but were expected to survive.
Area hospitals have treated several other Serratia infections at injection sites. "This is the first time in my 10 years with the board that we have seen contaminated products come out of a compounding pharmacy," said Virginia Herold, assistant executive officer of the California State Board of Pharmacy. "We're dealing with an issue that has great potential to damage public confidence in pharmacy."
Robert Horowitz, Doc's owner and chief pharmacist, did not return repeated telephone calls. According to local R.Ph.s, Doc's has developed a thriving compounding practice working with base products supplied by Professional Compounding Centers of America. PCCA supplies chemicals and other base materials to Doc's, said company president David Sparks in Houston, buying from the same bulk producers that supply Schering-Plough and other pharmaceutical manufacturers.
The betamethasone powder used by compounding pharmacies and manufacturers is not sterile, Sparks said. The final preparation is intended to be sterilized after reconstitution. Compounding pharmacies and manufacturers use filtering, autoclaving, or both, to sterilize the final solution.
According to county officials, Doc's Pharmacy prepared injectable betamethasone in 300-ml batches, then packaged the final product in vials for sale. All the reported infections have been linked to a single 300-ml batch.
County health officials suggested that a pharmacy technician may have accidentally set the autoclave incorrectly during compounding. In California, techs are allowed to compound under direct supervision of a pharmacist, but the supervising R.Ph. is responsible for the final product.
The pharmacy board and the state Department of Health Services are investigating the accident. Jon Rosenberg, M.D., head of the DHS division of communicable disease control, infection control, and healthcare epidemiology, said the two bodies would consider changes to pharmacy practice regulations governing compounding once they had identified all the factors that had contributed to the contamination and deaths.
Depending on their findings, the pharmacy, pharmacist, and technician could face a variety of administrative, civil, and criminal actions.
Validate procedures
Sparks cautioned pharmacists who compound injectables or other products to carefully review sterile procedures. Pharmacists should also validate their sterilization procedures, he said, in order to eliminate the potential for error. "This [contamination] could have happened with any injectable product," he said. "The same technique is used in compounding and in manufacturing. Manufacturing is just a bigger scale."
Quality-control and production problems shut down Schering-Plough's commercial production of its own branded betamethasone in early 2001. Betamethasone is most often used to relieve pain due to athletic injuries and other physical strains, said company spokesman Bob Consalvo. It is also commonly used to speed lung maturation in infants at high risk for premature birth. With the product in short supply, he said, Schering-Plough restricted sales and distribution to hospital-based neonatal units.
The shortage of Schering-Plough's betamethasone, combined with an unrelated shortage of dexamethasone, a common substitute for the treatment of sports-related injuries, pushed physicians and other healthcare providers to buy betamethasone compounded by pharmacists.
Consalvo said production problems are being rectified with the addition of new equipment, new procedures, and new manufacturing guidelines. Production should resume "shortly," he said, but pharmacies can expect a delay of several weeks as product moves through the distribution chain.
Please Note: Since I've posted this story, Schering has decided to discontinue making this drug for now. That's one down and two left to go!
These unfortunate deaths were caused by biological contaminants that were allowed to enter the drug manufacturing process. The Betamethasone was manufactured by a licensed "compounding pharmacy", a very controversial manufacturing procedure where the FDA's safety guidelines are NOT mandatory by law. A case can be made about these "cocktails" that make their way into the medical arena and harm patients, some fatally. It should be noted that biological meningitis is but ONE of the many causes of death and serious harmful effects when epidural steroid injections go wrong!
NATIONWIDE ALERT ON INJECTABLE DRUGS PREPARED BY URGENT CARE PHARMACY
The Food and Drug Administration (FDA) is announcing a nationwide alert concerning all injectable drugs prepared by Urgent Care Pharmacy of Spartanburg, South Carolina, based on the lack of assurance that their products are sterile. Non-sterility of injectable products can represent a serious hazard to health that could lead to life-threatening injuries and death. FDA inspection of Urgent Care's facility revealed the firm failed to have adequate controls to ensure necessary sterility, including the absence of appropriate testing for potency and sterility prior to distribution.
On September 16, 2002, Urgent Care recalled all lots of its injectable methylprednisolone acetate based on reports of four patients who developed a rare fungal (wangiella) meningitis (a life threatening infection of the lining of the brain and spinal cord) after use of their product. These patients were treated at three different North Carolina hospitals/clinics. Spinal fluid from all of these patients tested positive for a fungus consistent with that found in the Urgent Care product analyzed by both the FDA and Centers for Disease Control and Prevention (CDC). One patient later died despite antifungal therapy.
Urgent Care has refused to voluntarily recall any other injectable products they prepared and refused to provide FDA with a complete list of products they distributed. FDA is working to identify the recipients of these products so that the agency can directly alert them to the serious risks involved. FDA is continuing to work with the Centers for Disease Control, along with officials from both North Carolina and South Carolina, and will take whatever additional action is needed.
In the meantime, the South Carolina Board of Pharmacy has issued a Cease and Desist order to halt further sale of products from Urgent Care.
At the present time, based on limited information, FDA is aware that Urgent Care has distributed the following injectable drugs to physicians, hospitals, clinics and consumers in Connecticut, Illinois, Indiana, Kentucky, Louisiana, Massachusetts, Mississippi, New Hampshire, North Carolina, South Carolina and Virginia:
Baclofen
Betamethasone (Celestone Soluspan)
Bimix 30:1 (Phentolamine mesylate/papaverine)
Clonidine
Estradiol
Hydromorphone HCl
Fentanyl
Methylprednisolone acetate (Depo-Medrol)
Morphine Sulfate/Bupivacaine
Papaverine HCl
Super Trimix (Papaverine HCl/phentolamine mesylate/prostaglandin)
Testosterone cypionate
Testosterone/Estradiol
Urgent Care injectables are labeled as URGENT CARE PHARMACY 2500 WINCHESTER PLACE , STE. 106, SPARTANBURG, SC 29301, 800-692-8982.
Consumers, physicians, and health care workers are urged to examine their drug supplies for any Urgent Care injectable products and immediately discontinue their use. Users should also notify FDA of any complaints or problems associated with these products.
These reports may be made to MedWatch, the FDA’s voluntary reporting program, by phone at 1-800-FDA-1088 or on line at: http://www.fda.gov/medwatch/how.htm
