The company agreed to plead guilty to three criminal counts, including two counts of introducing misbranded drugs — Paxil and Wellbutrin — and one count of failing to report safety data about the drug Avandia to the Food and Drug Administration.

The $3 billion fine will be the largest penalty ever paid by a drug company, Deputy Attorney General James M. Cole said. The corporation also agreed to be monitored by government officials for five years to attempt to ensure the company’s compliance, Cole said.

Under the terms of the plea agreement, GSK(GSK) will pay a total of $1 billion, including a criminal fine of $956,814,400. The company also will pay $2 billion to resolve civil claims under the federal government’s False Claims Act.

“GSK’s sales force bribed physicians to prescribe GSK products using every imaginable form of high priced entertainment, from Hawaiian vacations to paying doctors millions of dollars to go on speaking tours to a European pheasant hunt to tickets to Madonna concerts, and this is just to name a few,” said Carmin M. Ortiz, U.S. attorney in Massachusetts.

“Today’s multibillion-dollar settlement is unprecedented in both size and scope,” Deputy Attorney General James Cole said. “At every level, we are determined to stop practices that jeopardize patients’ health, harm taxpayers, and violate the public trust – and this historic action is a clear warning to any company that chooses to break the law.”

Prosecutors said GlaxoSmithKline illegally promoted the drug Paxil for treating depression in children from April 1998 to August 2003, even though the FDA never approved it for anyone under age 18. The corporation also promoted the drug Wellbutrin from January 1999 to December 2003 for weight loss, the treatment of sexual dysfunction, substance addictions and attention deficit hyperactivity disorder, although it was only approved for treatment of major depressive disorder.

It is illegal to promote uses for a drug that have not been approved by the FDA — a practice known as off-label marketing.

“Let me be clear, we will not tolerate health care fraud,” Cole told a news conference at the Justice Department. He would not say whether any company executives were under investigation. The company’s guilty plea and sentence have to be approved by a federal court in Massachusetts.

“For far too long, we have heard that the pharmaceutical industry views these settlements merely as the cost of doing business,” Acting Assistant Attorney General Stuart F. Delery, head of Justice’s civil division, said at the news conference. “That is why this administration is committed to using every available tool to defeat health care fraud.”

Delery added, “Today’s resolution seeks not only to punish wrongdoing and recover taxpayer dollars, but to ensure GSK’s future compliance with the law.” He noted that a similar recent settlement with Abbott Laboratories also included continuing compliance monitoring.

Justice Department officials also said that between 2001 and 2007 GlaxoSmithKline failed to report to the FDA on safety data from certain post-marketing studies and from two studies of the cardiovascular safety of the diabetes drug Avandia. Since 2007, the FDA has added warnings to the Avandia label to alert doctors about potential increased risk of congestive heart failure and heart attack.

The drug corporation agreed to resolve civil liability for promoting the drugs Paxil, Wellbutrin, Advair, Lamictal and Zofran for off-label, non-covered uses. The company also resolved accusations that it paid kickbacks to doctors to prescribe those drugs as well as the drugs Imitrex, Lotronex, Flovent and Valtrex.

Of the penalties, $1 billion covers criminal fines and forfeitures and $2 billion is for civil settlements with the federal government and the state governments of Massachusetts and Colorado.

Glaxo is pleading guilty to these violations of FDA regulations, which are misdemeanors. It has set aside $3.5 billion to cover the cost of the fines and other penalties related to the government’s seven-year probe of the company’s marketing practices for Paxil, Wellbutrin and Avandia, three of its blockbuster drugs.

The company earlier set aisde $3 billion for legal costs tied to health problems that people taking Avandia and the other medicines are at risk of suffering.

Glaxo has already paid more than $700 million to resolve patient lawsuits, alleging Avandia caused heart attacks and strokes. Many of the Avandia cases have been consolidated before a federal judge in Philadelphia.