Understanding Pharmacokinetics and Pharmacodynamics: Sex-Related Differences

Lesson 5: Page 3 of 19

Pharmacodynamics and Pharmacokinetics : Understanding Pharmacokinetics and Pharmacodynamics: Sex-Related Differences

Sex-Specific Adverse Drug Events

More reports of adverse drug effects for women than for men were registered for 8 of the 10 prescription drugs withdrawn from the U.S. market between January 1997 and December 2000. The reason for the higher number of reports for women for several of these drugs might be because they were prescribed more often for women than for men: the weight loss drugs, Pondimin (fenfluramine) and Redux (dexfenfluramine), and the type 2 diabetes drug, Rezulin (troglitazone). However, another compelling explanation is that physiological differences between women and men may make women more susceptible to some drug-related health effects. For example, three drugs were withdrawn from the market because they were associated with a prolonged QT interval and an increased risk of developing a potentially fatal arrhythmia (torsades de pointes) in women: the non-sedating antihistamines Seldane (terfenadine) and Hismanal (astermizole), and Propulsid (cisapride), a drug for relief of nighttime heartburn.²

Table 1: Prescription Drugs Withdrawn From the United States Market, Jan. 1, 1997 Through Dec. 31, 2000

Drug	Type of Drug	Date Approved	Date Withdrawn	Primary Health Risk
Prescription Drugs With Evidence of Greater Health Risks in Women
Pondimin (fenfluramine hydrochloride)	Appetite suppressant	6/14/1973	9/15/1997	Valvular heart disease
Redux (dexfenfluramine hydrochloride)	Appetite suppressant	4/29/1996	9/15/1997	Valvular heart disease
Seldane^a (terfenadine)	Antihistamine	5/8/1985	2/27/1998	Torsades de pointes (potentially fatal irregular heartbeat)
Posicor (mibefradil dihydrochloride)	Cardiovascular	6/20/1997	6/8/1998	Lowered heart rate in elderly women and adverse interactions with 26 other drugs
Hismanal (astemizole)	Antihistamine	12/19/1988	6/18/1999	Torsades de pointes
Rezulin (troglitazone)	Diabetic	1/29/1997	3/21/2000	Liver failure
Propulsid^b (cisapride monohydrate)	Gastrointestinal	7/29/1993	7/14/2000	Torsades de pointes
Lotronex (alosetron hydrochloride)	Gastrointestinal	2/9/2000	11/28/2000	Ischemic colitis (intestinal inflammation due to lack of blood flow)
Prescription Drugs Without Evidence of Greater Health Risks in Women
Raxar (grepafloxacin hydrochloride)	Antibiotic	11/6/1997	11/1/1999	Torsades de pointes
Duract (bromfenac sodium)	Analgesic and anesthetic	7/15/1997	6/22/1998	Liver failure
^aSeldane-D was also withdrawn from the market Feb. 27, 1998. Terfenadine was the active ingredient in both Seldane and Seldane-D; Seldane-D also contained the decongestant pseudoephedrine. ^bPropulsid remains minimally available on a patient-by-patient basis for those with severely debilitating conditions. Source: GAO analysis.