The Food and Drug Administration said Monday two more drugs have been implicated in the ongoing outbreak of fungal meningitis linked to contaminated pain injections.
Both come from the same pharmacy, New England Compounding Center, that distributed the steroids suspected of sickening at least 214 people and killing 15 of them, the Food and Drug Administration said in a statement.
One is a steroid called triamcinolone acetonide and another is a product used during heart surgery. While the FDA hasn’t confirmed that the two products are to blame, it’s issued a warning.
Advertise | AdChoices“A patient with possible meningitis potentially associated with epidural injection of an additional NECC product, triamcinolone acetonide, has been identified through active surveillance and reported to FDA,” the agency said in a statement.
“Triamcinolone acetonide is a type of steroid injectable product made by NECC. The cases of meningitis identified to date have been associated with methylprednisolone acetate, another similar steroid injectable product.” Both can be injected into the spine. The FDA didn't specify what the triamcinolone was being used for in this case. Methylprednisolone was being used to treat pain.
Until now, just three lots of methylprednisolone made by NECC had been suspected – but as many as 14,000 patients were treated with steroid from those three batches.
“In addition, two transplant patients with Aspergillus fumigatus infection who were administered NECC cardioplegic solution during surgery have been reported,” the FDA added. “Cardioplegic solution is used to induce cardiac muscle paralysis during open heart surgery to prevent injury to the heart.”
The agency said it is still investigating. “FDA has not confirmed that these three infections were, in fact, caused by an NECC product,” it said.
“At this point in FDA’s investigation, the sterility of any injectable drugs, including ophthalmic drugs that are injectable or used in conjunction with eye surgery, and cardioplegic solutions produced by NECC are of significant concern, and out of an abundance of caution, patients who received these products should be alerted to the potential risk of infection,” FDA added.
“At this time, no cases of infection have been reported in connection with any NECC-produced ophthalmic drug that is injectable or used in conjunction with eye surgery, but FDA believes this class of products could present potentially similar risks of infection.”
The FDA has warned NECC about eye drugs before. In 2006 it issued a long and detailed warning letter to the pharmacy, saying it was going far beyond its licensed authority in packaging and compounding drugs.
It took a special interest in the company’s repackaging of Avastin, a cancer drug. Avastin stops tumors from growing by starving them of blood supply. It can also help treat a common form of blindness called wet macular degeneration using the same mechanism.
The drug’s maker, Roche, has a different formulation of Avastin that is packaged specifically to be injected into the eye. This drug, called Lucentis, costs as much as $2,000 per dose, compared to $150 a pop for Avastin when reformulated by a compounding pharmacist. NECC was taking Avastin and making an injectable version. The dose needed to treat the eye is much lower than the dose needed for treating colon and other cancers.
“FDA is particularly concerned about the manipulation of sterile products when a sterile container is opened or otherwise entered to conduct manipulations,” the agency said in its 2006 warning letter to NECC. “The moment a sterile container is opened and manipulated, a quality standard (sterility) is destroyed and previous studies supporting the standard are compromised and are no longer valid. We are especially concerned with the potential microbial contamination associated with splitting Avastin - a single-use, preservative-free, vial -- into multiple doses.”
Microbes that get into such an injection could damage vision or even blind patients. “The absence of control over storage, and delays before use after repackaging, only exacerbate these concerns,” the FDA said. It also warned NECC about other eye drugs it was preparing, and the latest notice appears to reflect those concerns.
Advertise | AdChoicesMeningitis is an inflammation of the membrane surrounding the brain and spinal cord. Symptoms include fever, headache, stiff neck, nausea and vomiting and sensitivity to light.
The Centers for Disease Control and Prevention updated its count of people affected by the outbreak. CDC says 214 people in 15 states have been infected. Most have meningitis, but two have infections apparently caused by steroid injections in the joints, including the ankle.
CDC also updated its guidance to doctors treating patients affected by the outbreak. Only patients who show clear signs of infection should be treated, the CDC says. At least two patients don’t have meningitis, but have evidence of infection from a steroid injection into a joint, including a patient in Michigan who was injected in the ankle.
Patients will likely have to undergo months of treatment with two antifungal drugs, voriconazole and amphotericin B. “Adequate duration of antifungal treatment is unknown, but patients likely will require prolonged therapy tailored by the clinical response to treatment,” CDC said.
But patients who have symptoms such as headache but who don’t show signs of inflammation should not get antifungal drugs, but should instead be watched carefully, the CDC advised. The two antifungal drugs can cause serious side effects, including kidney damage.
Federal officials recognized the doctors may be besieged and offered them a break. “We ask you to use your clinical judgment in deciding which patients are at risk and contact those patients in whatever communications mode you prefer, whether it is email, phone or letter. Face-to-face communication with patients is not necessary,” the FDA said.