The Food and Drug Administration said the stomach-soothing drug Prilosec cuts the blood-thinning effect of Plavix by half.
Regulators said the key ingredient in Prilosec blocks Plavix, known generically as clopidogrel, from taking full effect.
"Patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine," the agency said in a statement.
Because Plavix can upset the stomach, it is often prescribed with stomach acid-blocking drugs.
The FDA says patients who need to reduce their acid should take alternative drugs like Mylanta or Zantac.
Information about the drug interaction between Plavix and certain heartburn medications is not new. In January, Sanofi and Bristol-Myers updated Plavix's labeling to advise against using it in combination with certain heartburn drugs, following medical journal articles about the negative interaction.
A Sanofi spokeswoman said the company has now bolstered that labeling.
"We've strengthened the label to say that these drugs should be avoided altogether, not just discouraged," said Noelle Boyd, Sanofi's senior communications director.
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