“The drug manufacturer historically referred to HPP associated with Injectafer as asymptomatic but that is not true. A number of patients that have developed HPP after taking the drug have catastrophic problems,” says attorney Brenda Fulmer. “Liability in this case is that the manufacturer knew Injectafer was a problem before it was marketed in the U.S., but rather than withdraw it from the market, they kept tweaking the label but continued to minimize the risks in order to sell the product.”
Injectafer and the FDA
Fulmer says that Injectafer was denied twice after receiving from the FDA two non-approval letters requesting more testing and studies. It’s not unusual, however, to get denied on the first attempt and if different people are reviewing it there may be different opinions.
“[FDA] is like a blind traffic cop oblivious to what is happening, like an honor system where some agents put safety first while others will let the drug company continue to amend the label rather than pull it from the market,” explains Fulmer.
A lot of time is spent tinkering with these labels: the drug makers need to figure out how to add a warning without a flashing light. This process—going back and forth with the FDA on the label language --can take up to 12 months. Meanwhile the doctor and patient have no idea about the risks involved.
But we are doing better—a patient can request the package insert or review it online. Historically you wouldn’t receive anything in your meds packaging except the receipt, which does not include a comprehensive drug risks and precautions. Conversely, drug makers know patients aren’t reading the 14-page insert so they started producing consumer-friendly ‘patient information sheets’ or medication guides’, supposedly to give highlights of the risks and written in a language that most patients can understand.
“From a legal perspective regarding prescription drugs, the duty to warn goes from the manufacturer to the doctor and not necessarily directly to the patient,” says Fulmer.
Patients on Injectafer have only recently been tested for phosphate levels. Any patient on this medication is at risk for low-level phosphate, but the label doesn’t say you are at risk because you are taking this drug. From the Merck Manual:
Symptoms of hypophosphatemia occur only when the phosphate level in blood becomes very low. Muscle weakness develops, followed by stupor, coma, and death. In mild chronic hypophosphatemia, the bones can weaken, resulting in bone pain and fractures.
“Medications like Injectafer are mass marketed as a cure-all but, if they are allowed to remain on the market and not be recalled, we hope that they will become second-line therapy because other drugs are safer for most patients,” adds Fulmer. “We have got to make sure doctors get the information that risks outweigh the benefits for most patients based upon the published medical literature.” Some meds in the face of a change in the risk versus benefit calculation just disappear—a slow market withdrawal—because they are too risky and doctors are choosing better options for most of their patients.
Injectafer Label Change
The Injectafer label change in February 2020, which includes some of the latest information from the recent JAMA article, added low levels of phosphorous in your blood as possible side effects and heightened awareness of claims against the drug manufacturer for inadequate warnings from a legal standpoint.
“The label was recently enhanced to be more specific,” says Fulmer. Comprising 14 pages of tiny type, it is certainly detailed. And different parts of the label have different significance. It mentions HPP and a few words to doctors regarding who is at greater risk, but if doctors and patients had the time or inclination to read between the lines, they may become more aware of the risks involved. Prescribers would ask if there are safer options available for most patients. The answer is yes, so why use Injectafer with more potential side effects?
When there are label changes, doctors receive “Dear Doctor” letters. “In my experience taking depositions, doctors don’t always have the time to read amendments to drug warning labels. If it’s a new medication, they will spend time looking at the label and look at certain sections but it isn’t practical to read 14 pages together with patient,” says Fulmer. Thankfully many doctors subscribe to journals like JAMA and learn about potential safety issues through these publications, but that’s not perfect.
“Pharmaceutical sales reps are often unaware or told not to bring up potential safety issues with doctors during their sales calls,” says Fulmer. “If they don’t have the same safety profile as the competition, they will avoid this issue. When deposed, sales reps in general will say, ‘I am just here to sell the product’. They focus on important things to sell the product but skirt around safety. Sometimes the best information doctors have is when they talk to competing sales reps, who are more than happy to discuss adverse safety profiles of competing drugs, although this is not the most objective information for prescribing physicians either.”