The Swiss drug giant Novartis is paying $422.5 million to settle criminal and civil investigations into the marketing of the antiseizure medicine Trileptal and five other drugs, federal officials said on Thursday. Federal prosecutors accused Novartis of paying illegal kickbacks to health care professionals through speaker programs, advisory boards, entertainment, travel and meals. But aside from pleading guilty to one misdemeanor charge of mislabeling in an agreement that Novartis announced in February, the company denied wrongdoing. Novartis joins a growing list of pharmaceutical companies that have settled government investigations into health care fraud in the last few years, including Pfizer, which paid $2.3 billion; Eli Lilly, $1.4 billion; Allergan, $600 million; AstraZeneca, $520 million; Bristol-Myers Squibb, $515 million; and Forest Laboratories, $313 million. Pfizer, Lilly, Allergan and Forest and now Novartis -- pleaded guilty to crimes in the cases. The settlement includes a $170 million criminal fine and $15 million in criminal forfeiture by Novartis Pharmaceuticals, its U.S. subsidiary. The plea was announced by the office of the U.S. attorney in Philadelphia, which has specialized in health care fraud investigations of companies that promote drugs for uses not approved by the Food and Drug Administration, known as off-label marking. 'Off-label marketing can undermine the doctor-patient relationship and adversely influence the clear judgment that a doctor's patients have come to rely on and trust,' said Zane David Memeger, the U.S. attorney. Federal prosecutors said Novartis illegally promoted Trileptal for neuropathic pain and bipolar disease, singling out psychiatrists and pain specialists who were known to use the drug off-label. Physicians are legally permitted to use approved drugs for any purpose, but companies are prohibited from promoting them for conditions not authorized by the FDA. Novartis settled the investigation into the other drugs for $237.5 million. In a statement, Novartis said it had been cooperating with the investigations since 2005 and had already corrected its promotional practices. 'We are pleased to have reached resolution on this matter,' said Andy Wyss, president of Novartis Pharmaceuticals. He added that the company would 'continue its commitment to high standards of ethical business conduct and regulatory compliance in the sale and marketing of our products.' Erik Gordon, an assistant professor at the University of Michigan school of business who follows the drug industry, said it was 'easy to stifle a chuckle' when the company announced a guilty plea and, in the same news release, promised to continue ethical conduct. Prosecutors said top management at Novartis had approved illegal marketing from July 2000 to June 2004. No individual, however, was named or charged. Four whistle-blowers in the case will share more than $25 million under a government program intended to encourage company insiders to report illegal activity. Ruth R. Faden, a professor at the Bloomberg School of Public Health at Johns Hopkins and executive director of its Berman Institute of Bioethics, said off-label marketing undermined the government's work to ensure the safety of drugs. 'When drugs are in the market, they can be used for any indication at the discretion of the physician,' she said. 'But that's different from a situation in which companies make aggressive efforts to persuade physicians that there's value in a drug for which there is no evidence.' Novartis stock fell by about 1 percent an hour before the 1 p.m. announcement and closed at $57.67, down 0.53 percent. The five other drugs involved in the civil settlement are: Diovan, a hypertension drug that is the company's top-selling product, at $6 billion last year; Sandostatin, a drug to treat a growth hormone disorder that had worldwide sales of $1.2 billion last year; Exforge, a hypertension drug that sold $671 million; Tekturna, a blood pressure medicine that sold $290 million; and Zelnorm, a medicine for irritable bowel syndrome and constipation that was later withdrawn from the United States market. In a corporate filing last winter, Novartis said it was increasing reserves by $318 million in the fourth quarter, to a total of $397 million, to pay for pending settlements into past marketing practices. As part of the settlement, Novartis also signed a five-year corporate integrity agreement with the inspector general at the Department of Health and Human Services, which requires the company to monitor its sales practices and report any irregularities. Frank Lichtenberg, a Columbia professor who receives pharmaceutical financing for research on innovation in the industry, said off-label prescribing was encouraged by the American Medical Association and paid for by insurers, but off-label marketing was clearly illegal. 'So it's not surprising that they would settle because they don't have a legal leg to stand on,' he said. Lichtenberg said the nation might be seeing a peak in drug companies' settling such cases and the misconduct might decline in the future because of stepped-up enforcement and corporate integrity agreements. 