Amgen eventually tried to obtain approval for the less frequent dose, but the F.D.A. turned down its requests, saying the company’s studies were inadequate. Nonetheless, according to the federal charges, Amgen continued to promote the off-label dosing, relying on the same studies the F.D.A. had deemed inadequate.

Roger Burlingame, a federal prosecutor, told the judge Tuesday that “in certain instances, Amgen employees were so thoroughly indoctrinated to sell the drug for off-label uses that they did not, in fact, know that the drug had not been approved for the use for which they were selling it.”

A document summarizing the charges says that while sales representatives were not supposed to initiate discussions of off-label uses, they were trained to elicit questions from doctors. Such questions would provide the “necessary cover” for the sales representatives to provide the doctor with studies supporting the off-label use. Amgen referred to this as “reactive” marketing, the document said.

Amgen also managed to list the unapproved uses in a reference called a compendium. Medicare is required to pay for off-label uses of cancer drugs listed in an approved compendium. The compendium system is intended to make drugs more easily available to cancer patients, but critics say the compendiums do not adequately review the evidence.

Amgen issued a statement Tuesday acknowledging the guilty plea and noting that 14 months ago the company announced that it had set aside $780 million for the settlement of federal, state and whistle-blower complaints. Amgen’s stock fell 21 cents, to $89.29.

While doctors are allowed to use drugs for unapproved uses, companies are not supposed to promote such uses. The government has collected billions of dollars from pharmaceutical companies in recent years for off-label marketing.

The Amgen settlement is fairly large, but several have exceeded $1 billion. In July, GlaxoSmithKline agreed to pay $3 billion, in part for promoting antidepressants and other drugs for unapproved uses.