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Toxicology Litigation Support


VIOXX (rofecoxib) is a non-steroidal, anti-inflammatory drug referred to as a “COX-2 inhibitor” manufactured and marketed by Merck & Company. While Merck conducted major clinical trials on this drug, they were not forthright in disclosing the results which led to litigation related to cardiovascular and thrombotic events caused by Vioxx. The issue of causation is critical and meeting the causation criteria of the federal courts requires fulfilling the requirements of Daubert. Dr. Parent has written a causation report on Vioxx that has survived the Daubert challenge. More details on this drug may be found in the report and selected references provided below.

Selected References

Anonymous, Merck withdraws Vioxx; FDA issues public health advisory. F.D.A. Consumer, 38(6), 11 (2004).

Anonymous, Rofecoxib (Vioxx) withdrawal: do product monographs adequately inform physicians? Canadian Family Physician, 51, 212-213 (2005).

Bannwarth, B., Treves, R., Euller-Ziegler, L., Rolland, D., Ravaud, P. and Dougados, M., Adverse events associated with rofecoxib therapy: results of a large study in community-derived osteoarthritic patients. Drug Safety, 26(1), 49-54 (2003).

Berenson, A., Harris, G., Meier, B. and Pollack, A., Despite warnings, drug giant took, long path to Vioxx recall. N.Y. Times, November 14, A1, A32 (2004).

Bombardier, C., Laine, L., Reicin, A., Shapiro, D., Burgos-Vargas, R., Davis, B., Day, R., Ferraz, M. B.,  Hawkey, C. J., Hochberg, M. C., Kvien, T. K., Schnitzer, T. J. (VIGOR Study Group), Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. New England Journal of Medicine, 343(21), 1520-1528, 2 p following 1528 (2000).

Bresalier, R. S., Sandler, R. S., Quan, H., Bolognese, J. A., Oxenius, B., Horgan, K., Lines, C., Riddell, R., Morton, D., Lanas, A., Konstam, M. A., Baron, J. A. (Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators), Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. New England Journal of Medicine, 352(11), 1092-1102 (2005).

Campbell, R. J. and Sneed, K. B., Acute congestive heart failure induced by rofecoxib. Journal of the American Board of Family Practice, 17(2), 131-135 (2004).

Dalen, J. E., Selective COX-2 Inhibitors, NSAIDs, aspirin, and myocardial infarction. Archives of Internal Medicine, 162(10), 1091-1092 (2002).

Garattini, S. and Bertele, V., Discontinuation of Vioxx. Lancet, 365(9453), 24, author reply 26-27 (2005).

Geba, G. P., Weaver, A. L., Polis, A. B., Dixon, M. E., Schnitzer, T. J., Vioxx,  Acetaminophen, Celecoxib Trial (VACT) Group, Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial. Journal of the American Medical Association, 287(1), 64-71 (2002).

Grady, D., Herrington, D., Bittner, V., Blumenthal, R., Davidson, M., Hlatky, M., Hsia, J., Hulley, S., Herd, A., Khan, S., Newby,  L. K., Waters, D., Vittinghoff, E., Wenger,  N. (HERS Research Group), Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). Journal of the American Medical Association, 288(1), 49-57 (2002).

Horton, R., Vioxx, the implosion of Merck, and aftershocks at the FDA. Lancet, 463(9450), 1995-1996 (2004).

Immer, F. F., Immer-Bansi, A. S., Trachsel, N., Berdat, P. A., Eigenmann, V., Curatolo, M., Carrel, T. P., Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial. Ann. Thoracic Surgery, 75(2 ), 490-495 (2003).

Juni, P., Rutjes, A. W. and Dieppe, P. A., Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? British Medical Journal, 324(7349), 1287-1288 (2002).

Kammerl, M. C., Debler, J., Riegger, G. A. and Kramer, B. K., COX-2 inhibitors and risk of heart failure Lancet 2004;364(9444):1486-1487. Lancet, 364(9444), 1486-1487 (2004).

Langdon, P. E., Hankey, G. J. and Eikelboom, J. W., Cardiovascular safety of rofecoxib (Vioxx): lessons learned and unanswered questions. Medical Journal of Australia, 182(4), 199 (2005).

Lenzer, J., FDA advisers warn: COX 2 inhibitors increase risk of heart attack and stroke. British Medical Journal, 330(7489), 440 (2005).

Lisse, J. R., Perlman, M., Johansson, G., Shoemaker, J. R., Schechtman, J., Skalky, C. S., Dixon, M. E., Polis, A. B., Mollen, A. J., Geba, G. P. (ADVANTAGE Study Group), Author reply:  Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial. Annals of Internal Medicine, 140(12), 1060 (2004).

McLean, T. R., Discontinuation of Vioxx. Lancet, 365(9453), 25 (2005).

Nutt, D. J., Discontinuation of Vioxx. Lancet, 365(9453), 28 (2005).

Nyberg, J., Discontinuation of Vioxx. Lancet, 365(9453), 24-25, author reply 26-27 (2005).

Psaty, B. M. and Furberg, C. D., COX-2 inhibitors--lessons in drug safety. New England Journal of Medicine, 352(11), 1133-1135 (2005).

Ray, W. A., Stein, C. M., Daugherty, J. R., Hall, K., Arbogast, P. G., Griffin, M. R., COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet, 360(9339), 1071-1073 (2002).

Ruschitzka, F. T., The APPROVe study: what we should learn from the VIOXX withdrawal. Curr. Hypertension Reports, 7(1), 41-43 (2005).

Schnitzer, T. J., Burmester, G. R., Mysler, E., Hochberg, M. C., Doherty, M., Ehrsam, E., Gitton, X., Krammer, G., Mellein, B., Matchaba, P., Gimona, A., Hawkey, C. J. (TARGET Study Group), Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet, 364(9435), 665-674 (2004).

Sibbald, B., Rofecoxib (Vioxx) voluntarily withdrawn from market. Canadian Medical Association Journal, 171(9), 1027-1028 (2004).

Silverstein, F. E., Faich, G., Goldstein, J. L., Simon, L. S., Pincus, T., Whelton, A., Makuch, R., Eisen, G., Agrawal, N. M., Stenson, W. F., Burr, A. M., Zhao, W. W., Kent, J. D., Lefkowith, J. B., Verburg, K. M. and Geis, G. S., Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. Journal of the American Medical Association, 284(10), 1247-1255 (2000).

Torg, J., Vioxx and Merck: a preventable situation? Orthopedics, 28(3), 248, 250 (2005).

Wardle, E. N., COX-2 inhibitors and risk of heart failure. Lancet, 364(9444), 1487 (2004).

Waxman, H. A., The Lessions of Vioxx - Drug Safety and Sales. New England Journal of Medicine, 352, 2576-2578 (2005).

Whelton, A., Fort, J. G., Puma, J. A., Normandin, D., Bello, A. E., Verburg, K. M. (SUCCESS VI Study Group), Cyclooxygenase-2--specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. American Journal of Therapeutics, 8(2), 85-95 (2001).

Wright, J. M., The double-edged sword of COX-2 selective NSAIDs. Canadian Medical Association Journal, 167(10), 1131-1137 (2002).

Zhao, S. Z., Burke, T. A., Whelton, A., von Allmen, H. and Henderson, S. C., Comparison of the baseline cardiovascular risk profile among hypertensive patients prescribed COX-2-specific inhibitors or nonspecific NSAIDs: data from real-life practice. American Journal of Managed Care, 8(15 Suppl), S392-S400 (2002).

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