Anomalies in the dosing of diltiazem

AbstractFrom early research, investigators understood that the dose of diltiazem required for the treatment of hypertension (commonly 360 mg/day) was greater than that required for the treatment of angina (commonly 240 mg/day). Nonetheless, studies of recent prescribing practices show that the 240 and 180 mg capsule strengths constitute more than 70% of the diltiazem prescriptions for hypertension. Physicians became accustomed to the lower antianginal doses of diltiazem for 7 years before a hypertension indication was approved. Subsequently, these dosing levels were reinforced by the production of once‐a‐day formulations with highest capsule strengths of 240 mg and 300 mg. These strengths were dictated by the sheer bulk of the formulations, which limited how much diltiazem could be inserted into the #00 capsule, the largest capsule that can be comfortably administered. An examination of the combined data from the six randomized, blinded, and placebo‐controlled trials submitted to the FDA for the original new drug applications of the three formulations of diltiazem available in the United States shows a clear linear dose‐response relationship between diltiazem dose and blood pressur