Pfizer is making a multimillion-dollar bet that the over-the-counter (OTC) reflux market is worth a gander. The company said Tuesday that it’s scooping up worldwide marketing rights to the non-prescription version of AstraZeneca’s blockbuster proton-pump inhibitor, which AZ would start supplying to Pfizer’s consumer care unit upon the OTC med’s possible approval, for $250 million up front. The down payment could be a lead-in for additional milestone and royalty payments as the relationship continues.

The deal is a positive one for AstraZeneca, which has been slogging through a leadership change, massive layoffs and, most recently, a failed sepsis drug. A company statement indicated that Tuesday’s Nexium deal is also an entry point for further collaboration: AstraZeneca has given Pfizer first refusal rights for the OTC version of the hay fever spray Rhinocort Aqua.

Sales of Nexium’s prescription GERD medication, launched in the US in 2001, have been on the decline. Worldwide sales have fallen to $949 million during the first half of the year, a 13% drop compared to the same period last year. Annual sales faltered in 2011, with Nexium sales declining to $4.4 billion, 12% less than that drug’s sales in 2010. The drug is slated to lose US patent exclusivity in 2014.

“This agreement will help AstraZeneca realize the substantial, long-term value of this brand and potentially other brands in our portfolio,” Tony Zook, VP of global commercial optimization for AZ, said in a joint company statement. He added that Pfizer Consumer Healthcare is the “optimal partner to commercialise OTC Nexium globally.”

An OTC version of the drug has not yet been approved, and AstraZeneca will continue to manufacture the prescription version of the medication. An application for an OTC version of the drug went before European regulators in June. The companies said the FDA should expect to receive an OTC application in the first half of 2013. Pfizer said in the statement it expects to launch OTC Nexium in the US by 2014.

Pfizer’s not the only drugmaker looking to make money off of Rx-to-OTC switch opportunities. Sanofi is doing the same with allergy drug Allegra, an OTC version of which secured FDA approval last year, while Merck has been unsuccessful in several attempts to get OTC approval for its statin Mevacor. Pfizer itself was said to be weighing an attempt at an OTC switch for Lipitor last year.