|                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      | Pharmacy UpdateSeptember/October 1997
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | -------------------------------------
|In This Issue*Influenza

                        Vaccination*Troglitazone

                        (Rezulin): A Brief ReviewAugmentin: Twice Daily Dosing

Pharmacy Update Archives

Drug Information Service

                        Pharmacy Department

                        Warren G. Magnuson Clinical Center

                        National Institutes of Health

                        Bethesda, Maryland 20892-1196

                        Charles E. Daniels, Ph.D.

                        Chief, Pharmacy DepartmentEditor-in-Chief

                        Karim Anton Calis, Pharm.D., M.P.H.

                        Coordinator, Drug Information Service, and Endocrinology Clinical Pharmacy Specialist[email protected] | Influenza Vaccination: 1997-1998

                        Each year, infections due

                        to the influenza virus result in substantial morbidity and mortality worldwide. Vaccination offers appreciable

                        protection against the influenza virus for individuals and contributes to improved public health.

                        A new trivalent vaccine is now available for the 1997-1998 influenza season. The vaccine is recommended for patients

                        with chronic medical disorders, children with asthma, residents of long-term care facilities, and the elderly.

                        Health-care workers and household contacts of elderly and high-risk patients are also strongly encouraged to receive

                        the vaccine.

                        Protection conferred by the influenza vaccine typically begins two weeks after vaccination and may last for six

                        months or longer. Serum anti-bodies in some elderly patients can diminish more rapidly to non-protective levels.

                        Because large outbreaks in the United States usually occur between December and early March, the optimal time to

                        receive the vaccination is between October and November. However, administration of the vaccine is appropriate

                        anytime from September to the end of the influenza season.

                        The vaccine formulation is changed annually because of the antigenic variability of the influenza virus. Antigens

                        in the current vaccine are derived from A/Johannesburg/82/96 (H1N1), A/Nanchang/933/95 (H3n2)and B/Harbin/07/94.

                        Influenza vaccine is produced from inactivated virus grown in chicken eggs. Individuals who have experienced severe

                        hypersensitivity reactions to eggs or egg products should not receive the vaccine. An intramuscular dose of 0.5

                        mL of the split-virus formulation can be administered (in the deltoid)to adults and children at least three years

                        of age. Recipients of the vaccine may experience soreness at the site of injection, fever, and malaise that may

                        persist for one or two days.

                        Questions about influenza or the vaccine should be directed to the Hospital Epidemiology Service at 6-2209 or the

                        NIH Drug Information Service at 6-2407. For questions about the vaccination schedule, contact the Occupational

                        Medical Service at 6-4411.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
|Associate Editor

                        Amy M. Heck, Pharm.D.

                        Specialized Resident in Drug Information Practice and Pharmacotherapy[email protected]

ArchivesUp to Top                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      | Troglitazone (Rezulin®): A Brief Review

                        Troglitazone is the first of a new class of oral medications (thiazolidinedione derivatives) for the treatment

                        of non-insulin-dependent diabetes mellitus (NIDDM). It increases insu-lin sensitivity in skeletal muscle and adipose

                        tissue and decreases hepatic gluconeogenesis. Troglitazone was approved by the FDA on January 29, 1997 for the

                        treatment of NIDDM.

                        Description:Troglitazone (Rezulin®) is marketed by Parke-Davis

                        and is available as 200 mg, 300 mg, and 400 mg tablets.

                        Indications:Troglitazone is indicated for concomitant use with insulin

                        or a sulfonylurea to improve glycemic control in patients with NIDDM. Troglitazone may also be used as monotherapy

                        in patients with NIDDM not adequately controlled on diet alone.

                        Pharmacology:Troglitazone lowers blood glucose levels by improving

                        insulin sensitivity in target cells and inhibiting hepatic gluconeogenesis. Although the exact mechanism of action

                        is not fully understood, troglitazone is thought to bind to peroxisome proliferator-activated receptor gamma (PPAR?)

                        in the nucleus of hepatic muscle and adipose cells. PPAR? is involved in the transcription of certain genes that

                        regulate glucose and lipid metabolism. Binding of troglitazone to PPAR? is thought to activate transcription and

                        expression of certain genes that play a key role in proper carbohydrate and lipid metabolism. Troglitazone decreases

                        hepatic glucose synthesis and triglyceride synthesis and increases the uptake of glucose by skeletal muscle and

                        adipose tissue. These actions occur in the presence of insulin. Troglitazone does not affect insulin secretion.

                        Pharmacokinetics:Troglitazone is rapidly absorbed following oral

                        administration, with peak plasma concentrations occurring within 2-3 hours after oral administration. The presence

                        of food increases the extent of troglitazone absorption by approximately 30% to 85%. Therefore, it is recommended

                        that troglitazone be administered with a 

                        meal. In a study conducted in 21 healthy volunteers, the maximum plasma concentration (Cmax) and area-under-the-plasma-concentration

                        time curve (AUC) of troglitazone increased in proportion to increasing dose. The Cmax ranged from 0.90 μg/mL

                        to 2.82 μg/mL, and the AUC ranged from 7.4 μg.hr/mL to 22.1 μg.hr/mL with doses of 200 to 600

                        mg per day. Steady state plasma concentrations of troglitazone were obtained after 3-5 days of therapy, and the

                        mean apparent volume of distribution (Vd) of troglitazone was reported to be 10.5 - 26.5 L/kg. Troglitazone is

                        highly bound to serum albumin (>99%). It is extensively metabolized by the liver. Three troglitazone metabolites

                        have been identified: a sulfate conjugate (Metabolite 1), a glucuronide conjugate (Metabolite 2) and a quinone

                        metabolite (Metabolite 3). Troglitazone is primarily excreted in the feces (88%), and very small amounts have been

                        detected in the urine. The mean plasma elimination half-life of troglitazone ranges from 16-34 hours. Human in

                        vivo investigations have indicated that troglitazone may induce the cytochrome P450 3A4 enzyme pathway and could

                        result in clinically significant drug interactions.

                        Selected Clinical Studies:Troglitazone in combination with insulin therapy: Raskin et al studied 351 subjects with NIDDM who had failed

                        to maintain adequate diabetic control (HbA1C values ranging from 8.0% to 12.0%) with insulin doses > 30 units

                        per day. Subjects were randomized into three treatment groups to receive 200 mg of troglitazone (n = 116), 400

                        mg of troglita-zone (n =116), or placebo (n = 118) every morning. The primary outcome measures were the change

                        from baseline in HbA1C, fasting blood glucose, and insulin requirements. After 26 weeks of treatment, the adjusted

                        mean changes from base-line in both troglitazone treatment groups were significantly greater (p < 0.0001) than

                        those of the placebo group for all outcome measures.

                        Additional data on file from Parke-Davis indicate that 65% of subjects receiving troglitazone 600 mg, 48.3%

                        of subjects receiving troglitazone 200 mg, and 21.1% of subjects in the placebo group, were able to reduce their

                        daily insulin requirements by > 12.5% during this 26-week trial. In addition, 4 subjects who were treated with

                        600 mg of troglitazone completely discontinued exogenous insulin therapy. The incidence of reported adverse effects

                        was similar between both troglitazone treatment groups and the placebo group.

                        Gumbiner and colleagues conducted a similar multi-center, double-blind, placebo-controlled trial to evaluate

                        the efficacy of troglitazone in obese patients with non-insulin-dependent diabetes who were not adequately controlled

                        with insulin therapy. The primary treatment goal was to achieve a 50% reduction in total insulin requirements and

                        a >15% decrease in fasting blood glucose values. A total of 222 obese subjects (mean BMI > 35 kg/m2) with

                        NIDDM, who were receiving an average of 72 units of insulin per day, were randomized to receive troglitazone 200

                        mg (n = 75), troglitazone 400 mg (n = 76), or placebo (n = 71) once daily. After 26 weeks of treatment, 27% of

                        subjects in the troglitazone 400 mg group, 22% of subjects in the troglitazone 200 mg group, and 7% of the subjects

                        in the placebo group reached the target treatment goal for both insulin dose reduction and fasting blood glucose

                        values. This was statistically significant for both of the troglitazone treatment groups (p < 0.05). Parke-Davis

                        (data on file) reports that subjects in the troglitazone 200 mg and 400 mg groups decreased their total insulin

                        dosage by averages of 43% and 51%, respectively, and 15% of the subjects taking 400 mg of troglitazone were able

                        to discontinue insulin therapy. The mean change in the number of daily insulin injections was also reported as

                        -1.2, -1.4, and -2.0, for the placebo, troglitazone 200 mg, and troglitazone 400 mg groups, respectively.

                        Troglitazone in combination with a sulfonylurea: Troglitazone has also been evaluated in combination

                        with a sulfonylurea agent. Ghazzi and colleagues evaluated the efficacy and safety of combination therapy in 541

                        patients with NIDDM who were not controlled adequately on maximum doses of an oral sulfonylurea. Patients were

                        given 12 mg of Glynase® daily for 4 weeks. Subjects with fasting glucose values greater than 140 mg/dL at the

                        end of this 4-week baseline period were randomized to receive one of seven blinded treatments. These treatment

                        groups included Glynase® 12 mg, troglitazone 200 mg, troglitazone 400 mg, troglitazone 600 mg, Glynase®

                        12 mg and troglitazone 200 mg, Glynase® 12 mg and troglitazone 400 mg, and Glynase® 12 mg and troglitazone

                        600 mg daily. After one year of treatment, subjects receiving combination therapy with 

                        the sulfonylurea and troglitazone had the most significant decreases in HbA1c and fasting glucose levels. Specifically,

                        6.3% of subjects receiving Glynase® alone reached HbA1c values < 7.9% ,while 30.8%, 31.6%, and 57.5% of

                        subjects receiving Glynase® in combination with troglitazone 200 mg, 400 mg, and 600 mg doses, respectively

                        achieved HbA1c values < 7.9%. The incidence of adverse events and withdrawal rates were similar between all

                        treatment groups.

                        Iwamoto et al also studied the efficacy of troglitazone therapy in combination with sulfonylurea agents. Two-hundred

                        ninety-one Japanese patients with NIDDM and poor glycemic control, despite treatment with glibenclamide [glyburide]

                        or gliclazide, who had fasting plasma glucose levels higher than 8.3 mmole/L [149 mg/dL] were randomized to receive

                        either troglitazone 200 mg (n = 122) or placebo (n = 126) twice daily for 12 weeks. At the end of the treatment

                        period, there was a significant decrease in both fasting plasma glucose (10.8 + 2 mmole/L[195mg/dL + 36 mg/dL]vs

                        9.2 + 2.5 mmole/L[165mg/dL + 45 mg/dL]; p<0.001) and HbA1c values (9.2 + 1.4% vs 8.5 + 1.5%; p<0.001) in

                        the troglitazone treated group. These outcome measures were not altered in the placebo group. No serious adverse

                        events were reported with this drug combination and glycemic control was significantly improved.

                        Troglitazone as Monotherapy for NIDDM: Iwamoto studied 262 subjects with NIDDM and poor glycemic control

                        (fasting plasma glucose > 150 mg/dL) who were previously treated with diet therapy alone. Subjects were randomized

                        to receive either placebo (n = 126) or 400 mg of troglitazone (n = 136) for 12 weeks. Fasting plasma glucose (-23.4

                        mg/dL) and HbA1c values (-0.5%) were significantly decreased in the troglitazone treatment group and were unchanged

                        in the placebo group. A statistically significant decrease in trigly-cerides was also reported in the troglitazone-treated

                        group. This was only observed, however, in subjects who had high triglyceride values at baseline.

                        Information available in the FDA-approved product labeling reports unpublished data from a 6-month multi-center

                        study conducted in subjects wtih NIDDM who were previously treated with diet or sulfonylureas to evaluate the efficacy

                        of troglitazone monotherapy. A 2-week washout period was completed by all subjects prior to randomization. Subjects

                        were randomized to receive either placebo or trog-litazone 100 mg, 200 mg, 400 mg, or 600 mg once daily for 6 months.

                        Hemoglobin A1c and fasting glucose values were decreased in all of the troglitazone treatment groups and was statistically

                        significant for the 600 mg treatment group, but only for those patients who were previously treated with diet.

                        In patients who were previously treated with a sulfonylureas, troglitazone monotherapy did not result in an improvement

                        above that of the patients' previous therapy. Troglitazone also reduced triglycerides and fasting free fatty acids

                        and increased LDL cholesterol and HDL cholesterol. The cholesterol/HDL and LDL/Apo B ratios were unchanged in all

                        troglitazone treatment groups.

                        Troglitazone for the treatment of glucose intolerance: Several small studies have evaluated the effects

                        of troglitazone therapy in obese and insulin-resistant patients with impaired glucose tolerance. Nolan et al evaluated

                        oral and IV glucose tolerance tests in 18 non-diabetic obese patients (9 with impaired glucose tolerance) who were

                        randomized to receive either troglitazone 200 mg twice daily or placebo for 12 weeks. Subjects who received troglitazone

                        had an increased calculated insulin-sensitivity index, a decreased glycemic response, and a decreased fasting insulin

                        plasma concentration. There were no changes noted in the placebo group.

                        Forty-two Hispanic women with impaired glucose tolerance and a history of gestational diabetes mellitus were

                        randomized to receive placebo, 200 mg, or 400 mg 

                        of troglitazone. After 12 weeks of treatment, the calculated insulin sensitivity increased 40% + 22% for subjects

                        receiving 200 mg of troglitazone and 88% + 22% for subjects receiving 400 mg of troglitazone. Glucose tolerance

                        improved only slightly in all groups. The lack of significant improvement in glucose tolerance was attributed to

                        a beta-cell defect found in women with gestational diabetes.

                        Forty-six patients with impaired glucose intolerance, as defined by WHO criteria, were randomized to receive

                        either 400 mg of troglitazone or placebo for 12 weeks. Glucose, insulin, and C-peptide responses following oral

                        glucose tolerance tests were significantly reduced at about 6 and 12 weeks in the troglitazone treatment group,

                        with 75% of the troglitazone-treated subjects having normal glucose tolerance test at the end of 6 weeks and 80%

                        having normal glucose tolerance tests at the end of 12 weeks therapy.

                        Troglitazone has also been investigated in the treatment of other disorders which involve insulin resistance.

                        For example, a three- month study conducted in 25 women with polycystic ovary syndrome treated with either 200

                        mg of troglitazone or 400 mg of troglitazone reported increased insulin sensitivity, and two women began to have

                        ovulatory menses

                        Adverse Effects: Troglitazone therapy was well tolerated during clinical

                        trials, and the incidence of most reported adverse events related to troglitazone was similar to those reported

                        by the placebo group. Adverse events reported in >= 5% of patients receiving troglitazone during clinical trials

                        include headache, infection, pain, accidental injury, asthenia, dizziness, back pain, nausea, rhinitis, diarrhea,

                        urinary tract infections, peripheral edema, and pharyngitis.

                        During clinical trials, 20 patients were withdrawn from studies due to abnormalities in liver function tests,

                        including elevations in serum transaminase levels, hyperbilirubinemia, and two patients developed reversible jaundice.

                        Small decreases in hemoglobin, hematocrit, and neutrophil counts were observed more frequently in patients treated

                        with troglitazone. These decreases were usually not below the normal range and occurred within the first four to

                        eight weeks of therapy. These effects were not associated with any harmful clinical effects and the hemoglobin,

                        hematocrit, and neutrophils typically stabilized and remained within normal limits for up to 2 years of treatment.

                        Troglitazone treatment can result in an increased total plasma volume, which may explain a dilutional effect on

                        these hematological measures.

                        Studies conducted in rats treated with troglitazone doses ten times the therapeutic human dose resulted in reversible

                        heart enlargement. This effect has not been demonstrated during human clinical trials. Ghazzi evaluated this potential

                        adverse effect in 154 NIDDM patients who were treated with 800 mg of troglitazone or 20 mg - 40 mg of glyburide

                        for 48 weeks. There was no difference in left ventricular mass index from baseline measurements. Subjects treated

                        with troglitazone had significant increases in stroke volume index and cardiac index, as well as, decrease in diastolic

                        blood pressure and estimated total peripheral resistance.

                        Drug Interactions: Troglitazone may induce the cytochrome P450 3A4

                        enzyme system causing potentially clinically significant drug interactions with other medications such as astemizole,

                        calcium channel blockers, cisapride, corticosteroids, cyclosporine, HMG-CoA reductase inhibitors, tacrolimus, triazolam,

                        or trimetrexate. Concomitant administration of an oral contraceptive (containing ethinyl estradiol and norethindrone)

                        and troglitazone resulted in reduction in the plasma concentrations of both agents by approximately 30%. Concurrent

                        use of troglitazone is decreased by approximately 70% when administered with cholestyramine.

                        Troglitazone does not interact adversely with digoxin, glyburide, warfarin or acetaminophen.

                        Precautions and Contraindications:Troglitazone therapy is contradicted

                        in patients with known hypersensitivity to troglitazone or any of the components used in the tablet formulation.

                        Due to the extensive hepatic metabolism of troglitazone, it should be used with caution in patients with hepatic

                        disease.

                        Patients who are receiving concomitant therapy of troglitazone with sulfonylurea agents or insulin should be

                        monitored very closely for hypoglycemia since troglitazone can decrease the requirements for these hypoglycemic

                        agents.

                        Pharmacokinetic parameters of troglitazone and its major metabolites in elderly patients appear to be comparable

                        to those found in younger patients.

                        Patients with renal insufficiency do not require dosage adjustments of troglitazone, as clearance of the drug

                        is not related to creatinine clearance.

                        Dosage and Administration:

                        Monotherapy: The initial dose is 400 mg once daily taken with a meal. In patients who do not respond to 400

                        mg daily, the dose may be increased to 600 mg after 6-8 weeks of therapy.

                        Combination with a sulfonylurea: The initial recommended dose is 200 mg once daily with a meal. Troglitazone

                        dosage may be increased at 2-4 week intervals.

                        Combination with insulin: The initial recommended dose is 200 mg once daily taken with a meal. The troglitazone

                        dose may be increased to 400 mg daily of there is a lack of a clinical response at the end of 4 weeks of treatment.

                        Insulin dosage should be titrated based on individual response.

                        The maximum daily dosage of troglitazone is 600 mg.

                        Table 1. Cost comparison of troglitazone and various oral hypoglycemicsDrug

                                        Usual Dose Range

                                        Cost per month of therapy ($)**Glyburide*

                                        5 mg - 10 mg in single or divided daily doses

                                        0.55 - 3.40Glipizide

                                        10 mg - 20 mg in single or divided daily doses

                                        1.08 - 2.03Metformin*

                                        1500 mg - 2550 mg in divided doses

                                        28.87 - 36.73Acarbose

                                        50 mg - 100 mg three times daily

                                        28.49 - 36.73Troglitazone

                                        400 mg daily

                                        100.22* NIH CC Formulary Agents

                        ** Federal Supply Schedule

                        Conclusion: Troglitazone is a novel agent for the treatment of NIDDM

                        that decreases insulin in resistance. It appears to be safe and effective as monotherapy and in combination with

                        sulfonylureas or insulin. Troglitazone may prevent the progression to NIDDM in patients with impaired glucose tolerance.

                        References available upon request.

                        Editor's Note:



                        We wish to thank Crystal Blankenship, Pharm. D. for her contribution to this issue of Pharmacy Update | Drug                                 
|Drug                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    | Usual Dose Range                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     | Cost per month of therapy ($)**      
|Glyburide*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | 5 mg - 10 mg in single or divided daily doses                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        | 0.55 - 3.40                          
|Glipizide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | 10 mg - 20 mg in single or divided daily doses                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | 1.08 - 2.03                          
|Metformin*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | 1500 mg - 2550 mg in divided doses                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   | 28.87 - 36.73                        
|Acarbose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | 50 mg - 100 mg three times daily                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     | 28.49 - 36.73                        
|Troglitazone                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            | 400 mg daily                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | 100.22                               



---

|Drug Information Service*Patient-specific

                        medication information and pharmocotherapy consultations* Nutritional and metabolic

                        support consultations* Comprehensive information

                        about medications, biologics, nutrients, and drug therapy* Investigational drug information

                        (pre-clinical and clinical)* Research support and assistance

                        with study design, protocol development, and critical literature evaluation301-496-2407Pager 104-2619-7

                        Building 10, Room 1N257 | Augmentin: New, Twice-Daily Dosing

                        Augmentin® (amoxicillin & clavulanic acid), which has traditionally been dosed three times per day,

                        is now available in formulations designed for twice-daily (B.I.D.) dosing.  The Inpatient and

                        Outpatient Pharmacies will only stock the B.I.D. formulations. Augmentin® dosing is based on the amoxicillin

                        component of the product.

                        Products on formulary:875 mg amoxicillin & 125 mg clavulanic acid tablets

                        500 mg amoxicillin & 125 mg clavulanic acid tablets

                        400 mg amoxicillin & 57 mg clavulanic acid/5mL

                        oral suspension
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



---

Designed by Richard Barnes, NCRR, MAPB.

Comments or questions concerning this site? ContactPharmacy Webmaster.National Institutes of Health (NIH) , Warren Grant Magnuson Clinical Center (CC)

Pharmacy Department, Bethesda, Maryland 20892

Last updated: July 18, 1997

NIH Home Page|Clinical Center Home

Page|Pharmacy Home Page