History of Proton Pump Inhibitors
The most popular heartburn drugs on the market belong to a class called proton pump inhibitors (PPIs), and have been available in the United States for decades. Recently though, proton pump inhibitors have been linked to an increased risk of heart problems, kidney failure, dementia, and other serious injuries, and patients who believe they have been adversely affected by side effects of PPI drugs like Nexium, Prevacid and Prilosec are pursuing legal claims against the makers of the medications, alleging that they failed to provide adequate warnings about the risks of PPI side effects. Still, proton pump inhibitors are some of the most widely-used medications in the world, bringing in more than $14 billion in U.S. sales every year, and many are prescribed “off-label,” for uses not approved by the FDA. The following is a timeline of important events in the history of proton pump inhibitors.
Proton Pump Inhibitor Timeline
1970s – Evidence emerges that the newly discovered proton pump in the secretory membrane of the cells in the stomach is the final step in the secretion of gastric acid.
1975 – Timoprazole, a pyridylmethylsulfinyl benzimidazole, is found to inhibit acid secretion in the stomach.
1979 – A derivative of timoprazole, called omeprazole (Prilosec) is discovered, and is the first of a new class of medications designed to control the secretion of stomach acid, called proton pump inhibitors (PPIs).
1980 – An Investigational New Drug (IND) application is filed for omeprazole.
1982 – Omeprazole is taken into Phase III human trials.
1987 – Astra launches a new research program to identify a new analogue to omeprazole with less variability between patients, and finds only one compound superior to omeprazole, esomeprazole.
1990 – Omeprazole is introduced in the United States under the brand name Prilosec.
1995 – Lansoprazole (Prevacid) is launched in the United States.
1999 – Rabeprazole (AcipHex) is launched in the United States.
2000 – Pantoprazole (Protonix) is launched in the United States.
2000 – Esomeprazole garners approval from the U.S. Food and Drug Administration (FDA), under the brand name Nexium, and enters the market in the United States as a follow-up of omeprazole’s patent.
2006 – Santarus, Inc. announces the U.S. launch of Zegerid, an omeprazole/sodium bicarbonate combination drug.
December 2006 – The Journal of the American Medical Association publishes a study tying long-term use of PPI drugs to a higher risk of hip fractures in patients over the age of 50.
2009 – Dexlansoprazole (Kapidex, Dexilant) is launched in the United States as a follow-up of lansoprazole.
May 2010 – A study published in the Archives of Internal Medicine finds that post-menopausal women who take PPIs may be 25% more likely to experience a bone fracture side effect.
May 2010 – The FDA requires the makers of proton pump inhibitors to update their drug warning labels to include the risk of bone fractures associated with the heartburn medications.
2011 – An Ohio woman files a Nexium lawsuit against AstraZeneca over her bone fracture injuries.
March 2011 – A drug safety communication issued by the FDA warns that “prescription proton pump inhibitor (PPI) drugs may cause low serum magnesium levels (hypomagnesemia) if taken for prolonged periods of time.”
2012 – A Prevacid lawsuit is brought against Takeda Pharmaceuticals, alleging that the company failed to warn about the risk of bone fracture side effects from the drug.
April 2012 – Health officials in the UK warn that long-term use of proton pump inhibitors may increase the risk of bone fractures and result in dangerously low levels of magnesium in the body.
2013 – Pfizer agrees to a $55 million settlement with the U.S. government to resolve allegations that the company promoted Protonix for inappropriate uses.
July 2013 – The medical journal Circulation publishes research indicating that Nexium, Prevacid and other popular heartburn drugs may increase the risk of cardiovascular problems in patients.
2015 – Prilosec maker AstraZeneca pays $20 million in a class action lawsuit alleging that the company created a drug nearly identical to Nexium and charged users an exorbitant fee for the medication.
2016 – The first Nexium kidney damage lawsuit is filed against AstraZeneca.
April 2016 – A study published in JAMA Neurology warns that proton pump inhibitors may increase the risk of dementia in users by as much as 44%.
April 2016 – The Journal of the American Society of Nephrology publishes a study indicating that patients taking PPI drugs may face an increased risk of chronic kidney disease and end-stage kidney failure.
May 2016 – Proton pump inhibitors may increase the risk of bone loss and osteoporosis, according to research published in the International Journal of Rheumatic Diseases.