Blockbuster status is the Holy Grail for drug developers, but patent expirations mean these billion-dollar drugs have a limited shelf life. These three drugs, for example, have been among the planet's best-sellers, but over the course of the next five years, our analysts believe their sales could dwindle to a trickle.

Todd Campbell: Since the 1950's, doctors have turned to warfarin, sold by Bristol-Myers Squibb (NYSE:BMY) as Coumadin, to keep blood flowing freely in heart disease patients and after hip and knee surgeries.

However, Coumadin's long standing dominance has been weakened in recent years by a new generation of anticoagulants that claim to work better, and with fewer risks. These Factor Xa inhibitors, led by Johnson & Johnson's (NYSE:JNJ) Xarelto and Bristol-Myers and Pfizer's (NYSE:PFE) Eliquis, have seen their sales grow remarkably in the past year. J&J's Xarelto sales increased by 76% to $1.5 billion, and Bristol-Myers and Pfizer's Eliquis sales surged from $146 million to $774 million in 2014.

Yet despite the sales growth these drugs have enjoyed, their revenue could still go much higher. Industry experts peg the market for anticoagulants at north of $10 billion annually, and many doctors continue to use Coumadin instead of Factor Xa drugs for one important reason: There's no approved antidote to the Factor Xa drugs, putting patients at risk in the event of emergency surgery or a bleeding situation. However, that could soon change. Portola Pharmaceuticals (NASDAQ:PTLA) has reported positive phase 3 trial results that show its drug andexanet alfa reverses the effect of both Xarelto and Eliquis. If that data holds up, and andexanet alfa can win FDA approval, Coumadin could find itself in the dustbin.

Cheryl Swanson: GlaxoSmithKline's (NYSE:GSK) former $7 billion a year drug Advair is aging so rapidly, it's more than likely to kick the bucket within five years. Sales of the inhaled asthma and COPD drug plunged more than 25% last quarter in the U.S., fueling an overall 11% pharmaceutical sales slide for Glaxo.

Advair's 2001 product launch was one for the record books, and it's no wonder. Advair was a major breakthrough, combining two effective agents, one to treat airway constriction, and the other to treat inflammation.

Advair is already off patent in the U.S., but a separate patent on its sophisticated inhaler device should remain in place until the end of 2016. By contrast, Advair's EU patent expired in 2013, opening the door to generics such as Novartis' AirFluSal Forspio. British pharma Glaxo has been counting on two follow-up drugs to fill Advair's shoes. But those drugs -- Breo and Anoro -- have had lackluster launches.

Meanwhile, Express Scripts, the nation's largest pharmacy benefits manager, dropped Advair from its formulary last year. Glaxo did some heavy-duty discounting to get the drug reinstated in 2015, but the result was a 15% toll on the drug's national top-line haul, according to FiercePharma.

Advair's sales slide is in large part responsible for a $1.6 billion cost-cutting binge at Glaxo, including the loss of at least 900 sales and research jobs in the U.S. With competition rapidly eroding market share, and payers requiring deep discounts, this is one drug that poet T.S. Eliot, who suffered from lung problems himself, might say is going to end "not with a bang, but a whimper."

Brian OrelliTeva Pharmaceuticals' (NYSE:TEVA) multiple sclerosis drug Copaxone has quite a few threats that could knock the $3.5 billion drug off its pedestal.

First, there's potential for generic competition. The main patent on Copaxone has already expired, but Teva claims other patents that cover the drug. Lawsuits by Novartis' generic drug division Sandoz and others to invalidate the extra patents have had mixed results. The Supreme Court recently sent a court case back to a lower court for further review.

Even if the patents are found invalid, the FDA hasn't approved a generic version of Copaxone because its complicated structure makes it hard to confirm the copycats are close enough to the original version to work in the same way. The application for Novartis and its partner Momenta Pharmaceuticals' generic version has been under review since 2008. It's possible the agency will be more motivated to rule on the generic applications once the patent situation is worked out.

To counter the potential generic threat, Teva is trying to switch patients over to a version of Copaxone that only has to be injected three times a week rather than daily. The longer the patent and generics-related FDA issues drag on, the more time Teva has to get patients to switch.

While the move from once daily to three times weekly is a good proposition for patients, there are many other drugs multiple sclerosis patients can take, including Biogen Idec's Tecfidera, which is taken orally, and Biogen's Plegridy, which only has to be injected every other week. In any case, the competition will likely continue to put a damper on Copaxone sales. 

Brian Orelli has no position in any stocks mentioned. Cheryl Swanson has no position in any stocks mentioned. Todd Campbell has no position in any stocks mentioned. The Motley Fool recommends Express Scripts, Johnson & Johnson, Momenta Pharmaceuticals, and Teva Pharmaceutical Industries. The Motley Fool owns shares of Express Scripts and Johnson & Johnson. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.