for Enbrel in the U.S. and Canada in October 2013, which resulted in a decrease in operational revenues of $1.4 billion in 2014, compared to 2013. (While Enbrel alliance revenues declined $1.4 billion in 2014, we received royalty income from Enbrel in the U.S. and Canada of $531 million in 2014, an operational increase of approximately $440 million, which is recorded in Other (income)/deductions—net in the consolidated statements on income. See Notes to Consolidated Financial Statements—Note 4. Other (Income)/Deductions—Net.);

the expiration or near-term expiration of the co-promotion collaboration for Spiriva (GEP) in Japan, the U.S. (where the collaboration expired in April 2014), certain European countries, Australia, Canada and South Korea, which resulted in an operational decrease in Pfizer's share of Spiriva revenues of $490 million in 2014, compared to 2013; and

the loss of exclusivity for Aricept in Canada in December 2013 and the termination of the co-promotion agreement in Japan in December 2012, which resulted in an operational decrease in Pfizer's share of Aricept revenues of approximately $137 million in 2014, compared to 2013,

partially offset by

an increase of $266 million for Eliquis worldwide revenues.

• Eliquis (apixaban) (GIP) is being jointly developed and commercialized by Pfizer and Bristol-Myers Squibb (BMS). Eliquis is part of the Novel Oral Anticoagulant (NOAC) market; the agents in this class were developed as alternatives to warfarin in appropriate patients with certain conditions. In 2012, Eliquis (apixaban) was approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) in the U.S., Europe and Japan. Since then, the NVAF indication has been launched in the majority of markets around the world. In addition, Eliquis is approved in the U.S. and Europe for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for the reduction in the risk of recurrent DVT and PE following initial therapy as well as for the prophylaxis of DVT, which may lead to PE, in patients who have undergone hip or knee replacement surgery. The two companies share commercialization expenses and profit/losses equally on a global basis. While Eliquis was the third entrant in this market, we believe it has a differentiated product profile and continue to invest in medical education and peer-to-peer programs to assist physicians in understanding the data, and in direct-to-consumer advertising in the U.S.

• Embeda (GIP)—In November 2013, we announced that the FDA had approved a prior approval supplement for an update to the Embeda manufacturing process. This update addressed the pre-specified stability requirement that led to the voluntary recall of Embeda from the market in March 2011. In October 2014, the FDA approved an updated label for Embeda extended release capsules, for oral use, to include abuse-deterrence study data. Embeda is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Embeda became available in the U.S. in February 2015.

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