Nitroprusside, Isoproterenol Use Plummets After Price Hikes

Patrice Wendling

August 14, 2017

CLEVELAND, OH — In the wake of staggering price increases, the number of patients receiving the heart drugs nitroprusside (Nitropress, Valeant Pharmaceuticals) and isoproterenol (Isuprel, Valeant Pharmaceuticals) has fallen dramatically by 53% and 35%, respectively, according to a study published in the New England Journal of Medicine[1].

Dr Umesh Khot (Cleveland Clinic, OH) and colleagues tracked use of the two drugs in 47 US hospitals from 2012 to 2015—a period where the wholesale acquisition cost (WAC) increased by about 3000% for nitroprusside ($27.46 to $880.88 per 50 mg) and by about 7000% for isoproterenol ($26.20 to $1790.11 per mg).

The drug maker, which acquired the drugs from Marathon Pharmaceuticals in 2015, argued last year during a US congressional probe that the controversial price increases would have a limited impact on most hospitals.

Its then-CEO Howard Schiller stated, "Because these drugs are hospital-administered and not purchased by patients directly, increasing the costs of the drugs to hospitals would affect the hospital's profits on these procedures, but it should not reduce patient access."[2]

"For these drugs, it's conclusive that what was not supposed to happen did, and it happened in a very short period of time, within 2 years of the price increases," Khot told | Medscape Cardiology.

He added high costs are often linked to brand-name drugs or new discoveries, but "what's really unusual is that these drugs are very old, they've been on the market for decades; so the price increases on these types of drugs are something we've only seen in the past 5 years."

Despite routine use of nitroprusside to treat congestive heart failure and hypertension and isoproterenol to treat heart block and bradycardia, the results also suggest a shift in prescribing patterns to two other intravenous heart drugs with somewhat similar effects but more stable pricing.

From 2012 to 2015, the WAC or list price remained under $20 for nitroglycerin ($5.92 to $17.57 per 50 mg) and for dobutamine ($17.78 to $16.50 per g).

After comparing the four drugs, the investigators found the number of patients treated with nitroprusside per 1000 inpatients per hospital declined by 46% (9.30 to 4.99; P<0.001), while the corresponding number increased 89% for patients treated with nitroglycerin (16.17 to 30.55; P<0.001).

The number of patients treated with isoproterenol per 1000 inpatients per hospital declined by 40% (2.76 to 1.65; P<0.001), while the corresponding number increased 4% for patients treated with dobutamine (8.02 to 8.31; P=0.74).

"When we looked at this internally, we spent a large amount of time thinking and trying to come up with 'what are the options' and actually also decided on which patients is substitution not an option," Khot said. "For example, we have two conditions—when we use this [nitroprusside] in severe heart failure and when we use this [isoproterenol] during electrophysiology procedures—where we made the decision we would not substitute anything and we would protect patient access, whereas in other situations we looked for other options."

Valeant Pharmaceuticals would not answer specific questions from | Medscape Cardiology but noted in a prepared statement that it implemented an enhanced discount and rebate program in May 2016 for Nitropress and Isuprel for all US hospitals, with rebates ranging up to 40%.

"In addition, we have made a commitment that the average annual price increase for our prescription pharmaceutical products will be set at no greater than single digits and below the 5-year weighted average of the increases within the branded biopharmaceutical industry," the statement said.

"The current management team is committed to ensuring that past decisions with respect to product pricing are not repeated, and we believe these actions demonstrate that we are taking our approach to responsible pricing seriously."

The investigators concluded, "These findings refute the claim the price increases do not reduce patients' access to these medications. Decreasing demand also indicates a correcting market response to increased prices that may be a valuable restraining force to pharmaceutical price increases."

Notably, during the 2016 congressional hearing, Valeant stated that nitroprusside and isoproterenol "sales volumes have fallen by a greater degree—about 30% for each drug—than was anticipated at the time of the price increase" and that it expects both off-patent drugs "will likely be subject to generic competition in the not-too-distant future."

Of special note, the FDA announced Friday that it has approved the first generic version of Isuprel.

The study was supported by unrestricted philanthropic funding to the Heart and Vascular Institute Center for Healthcare Delivery Innovation, Cleveland Clinic. Khot reports personal fees from AstraZeneca, outside the submitted work. The coauthors report no relevant financial relationships.

Follow Patrice Wendling on Twitter: @pwendl. For more from | Medscape Cardiology, follow us on Twitter and Facebook.


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