Anomalies in the dosing of diltiazem

From early research, investigators understood that the dose of diltiazem re quired for the treatment of hypertension (commonly 360 mg/day) was greater than that required for the treatment of angina (commonly 240 mg/day). Nonet heless, studies of recent prescribing practices show that the 240 and 180 m g capsule strengths constitute more than 70% of the diltiazem prescriptions for hypertension. Physicians became accustomed to the lower antianginal do ses of diltiazem for 7 years before a hypertension indication was approved. Subsequently, these dosing levels were reinforced by the production of onc e-a-day formulations with highest capsule strengths of 240 mg and 300 mg. T hese strengths were dictated by the sheer bulk of the formulations, which l imited how much diltiazem could be inserted into the #00 capsule, the large st capsule that can be comfortably administered. An examination of the comb ined data from the six randomized, blinded, and placebo-controlled trials s ubmitted to the FDA for the original new drug applications of the three for mulations of diltiazem available in the United States shows a clear Linear dose-response relationship between diltiazem dose and blood pressure loweri ng through the 480-540 mg/day range. It also demonstrates that the 90-120 m g/day range is the "no-effect dose." These conclusions are supported by a M EDLINE review of all other studies of multilevel dosing of higher dose leve ls of diltiazem. The data support the conclusion that diltiazem is generall y underdosed, but when properly dosed may be the single most potent antihyp ertensive overall.