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The growing case against IV Tylenol, once seen as a solution to the opioid crisis

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In the midst of the opioid crisis, Boston Medical Center added an intravenous version of Tylenol to its arsenal of drugs for pain management. But IV Tylenol was expensive, and after drugmaker Mallinckrodt Pharmaceuticals increased the price, the hospital projected it was on track to spend $750,000 in 2015 on acetaminophen (the active ingredient in Tylenol) in injectable form.

"It was going to cost us, without the intervention that happened, more than any other drug on our formulary. Think of the most expensive cancer drug,” said David Twitchell, Boston Medical Center’s chief pharmacy officer. “To me, that didn’t seem justified.”

A typical dose of acetaminophen in tablet form costs pennies, but the IV version, called Ofirmev, is $40 for a 1,000-milligram dose.

Hospitals throughout the country are working to shift away from opioids, whose addictive properties have spawned a public health crisis.

Recent IV formulations of old drugs such as acetaminophen may present new options in managing pain while fighting the opioid crisis, but a growing body of evidence — including a new study — suggests that IV acetaminophen appears to offer little or no benefit over taking the same drug in pill form for many conditions. There are also studies that suggest a modest benefit, but many hospitals have limited access to the drug to patients who are incapable of taking oral medications due to its high cost and the inconsistent evidence of a clear advantage.

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The rapid uptake of IV acetaminophen, which accounted for more than $300 million in sales last year for Mallinckrodt, reveals how new drugs can ride a wave of novelty and marketing before their best real-world uses are fully understood. 

The study, published in the July issue of the journal Anesthesiology and based on seven years of claims data for bowel surgeries from 602 hospitals, found that IV acetaminophen appeared no better in reducing opioid use than taking the medicine orally.

“It just seems very often, physicians have magical thinking about a new preparation of an old drug,” said Andrew Leibowitz, system chair of the department of anesthesiology, perioperative and pain medicine at the Icahn School of Medicine at Mount Sinai, who co-authored the study. “Doctors do seem, in general when a patient is in the hospital, to favor IV medications as a knee-jerk reflex, even when equally effective oral medications are available.”

In a statement, Mallinckrodt dismissed the study as "significantly flawed" and pointed to journal articles that found IV acetaminophen associated with reduced hospital costs and decreased opioid use. The company pointed out that half of the patients who received IV acetaminophen in the colon surgery study received only one dose — only a quarter of the federally approved dose.

But that data reflects how hospitals are using the drug in the real world. Boston Medical Center was able to rein in its use of IV acetaminophen, partly by allowing only a single dose after surgery unless doctors sought further authorization.

"Based on the review evidence available, it doesn’t seem like the IV formulations are significantly better than oral formulations of these medications," said Will Vincent, a clinical pharmacy specialist for Boston Medical Center. "For some of our patients who are critically ill, if we’re not able to use oral medications, we're forced to use the injectable route."

Other IV formulations of generic painkillers exist — and more are expected to become available. Steven Lucio, associate vice president at the Center for Pharmacy Practice Excellence at Vizient, a company that negotiates contracts for drugs and medical supplies for hospitals each year, said that health-care providers will have to decide whether these more expensive drugs are truly more valuable.

"Just putting acetaminophen in an IV form doesn’t seem to correlate with a huge, demonstrable benefit that is repeatable," Lucio said. "Some studies show a little bit of benefit; some studies don’t show benefit."

Leibowitz and a co-author, Jashvant Poeran, said that because drug approvals are based on specific clinical trials, they do not always capture all the challenges of using a drug in real-world circumstances.

The team found that pain-management practices were startlingly variable, even for relatively routine surgery. That could reflect the still-evolving scientific and medical understanding of how to treat pain.

Erin Krebs, a staff physician at the Minneapolis Veterans Affairs Health Care System, led a study published in the Journal of the American Medical Association earlier this year that found opioids were no better at managing chronic back pain or hip and knee pain than non-opioid pain treatments. She said that physicians are, for good reasons, rethinking their use of opioids, but the urgency to use alternatives could make them susceptible to a pitch about a new drug, whereas older medicines don't typically have a sales force behind them.

"I think part of the reason we got into such a mess with opioids was really a lack of training and understanding of pain management," Krebs said. "It’s a symptom of how little research we've done on the appropriate management of these really common conditions. These are some of the most common human ailments, and they have not received enough research attention, research funding or education."

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