Back before the regulatory hammer came down in the 1960s, fixed combinations were mostly a motley bunch that included bizarre pairings of tranquilizers with just about anything. Today that's all changed, and it keeps getting better. Drugs made by combining established single agents aren't just respectable; several of them are major blockbusters. GlaxoSmithKline's Advair and Merck's Vytorin are the biggest successes, with more than $5 billion and $2 billion in annual sales, respectively. At least four other fixed combinations have surpassed the $1 billion mark for annual sales.

Those numbers have encouraged a bandwagon effect, and now more and more companies are combining popular single-agent treatments as new products. But not all fixed combinations are big winners. So what separates the winners from the losers? It helps to analyze and compare some examples.

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