Introduction
Tiazac, a once-a-day extended-release formulation of diltiazem hydrochloride, is a crucial medication for the treatment of hypertension and chronic stable angina. Here, we will delve into the clinical trials, market analysis, and projections for this drug.
Clinical Trials Overview
Hypertension Trials
Clinical trials have consistently shown that Tiazac is effective in reducing blood pressure. In short-term, double-blind, placebo-controlled studies involving 256 hypertensive patients, Tiazac demonstrated a dose-related antihypertensive response. The drug reduced supine diastolic blood pressure significantly, with reductions ranging from -6.3 mm Hg at 90 mg/day to -11.8 mm Hg at 540 mg/day compared to placebo[1].
Angina Trials
In patients with chronic stable angina, Tiazac increased exercise tolerance times. A double-blind, parallel-group, placebo-controlled trial showed that Tiazac at doses of 120 to 540 mg/day increased exercise tolerance times by 14 to 64 seconds over baseline at peak and trough levels[1].
Pharmacokinetics and Pharmacodynamics
Tiazac exhibits non-linear pharmacokinetics, with a more than proportional increase in diltiazem plasma concentrations as the daily dose increases from 120 to 540 mg. This results in higher AUC, Cmax, and Cmin values, indicating effective drug delivery[1].
Market Analysis
Competitive Landscape
The market for once-a-day diltiazem products is competitive, with Tiazac competing against other brands like Cardizem CD and Dilacor XR. However, Tiazac has faced regulatory and competitive challenges. The Federal Trade Commission (FTC) intervened to ensure competition in the market, particularly after Hoechst AG's merger with Marion Merrell Dow (MMD), which could have delayed the entry of Tiazac into the market[2].
Regulatory Issues
Biovail Corporation, the developer of Tiazac, was charged by the FTC for illegally acquiring an exclusive patent license to block generic competition. The consent order required Biovail to divest part of its exclusive rights and prohibited wrongful listing of patents in the FDA's "Orange Book" to block generic approvals[5].
Market Projections
Consumer Impact
The FTC's actions to ensure competition in the diltiazem market are projected to save consumers between $15 and $30 million annually. This is due to the removal of barriers that interfered with the effective entry of Tiazac, leading to lower prices for consumers suffering from hypertension and cardiac disease[2].
Generic Competition
The anticipated entry of generic versions of Tiazac is expected to further reduce prices and increase market competition. However, it is important to note that different sustained-release mechanisms of various diltiazem products may not make them generically equivalent, which could affect their market dynamics[3].
Pharmacokinetic Comparisons
Relative Bioavailability
A study comparing the relative bioavailability of Tiazac and Cardizem CD found that Tiazac had a higher Cmax and AUC after single doses but similar values at steady-state. However, Tiazac had a lower trough concentration and higher fluctuation in plasma concentrations compared to Cardizem CD[4].
Adverse Reactions and Contraindications
Common Adverse Reactions
Clinical trials have shown that Tiazac is generally well-tolerated, with common adverse reactions including first-degree AV block, dizziness, and headache. Serious adverse reactions are rare but can include exacerbation of heart failure in patients with impaired ventricular function[1].
Contraindications
Tiazac is contraindicated in patients with sick sinus syndrome (except in the presence of a functioning ventricular pacemaker), second- or third-degree AV block, acute myocardial infarction, and pulmonary congestion. It is also contraindicated in patients who have demonstrated hypersensitivity to the drug[1].
Key Takeaways
- Efficacy: Tiazac is effective in reducing blood pressure and increasing exercise tolerance in patients with hypertension and chronic stable angina.
- Market Competition: Regulatory actions have ensured competition in the diltiazem market, leading to potential cost savings for consumers.
- Pharmacokinetics: Tiazac exhibits non-linear pharmacokinetics and has different pharmacokinetic profiles compared to other diltiazem formulations.
- Safety: Tiazac is generally well-tolerated but has specific contraindications and potential adverse reactions.
FAQs
What is Tiazac used for?
Tiazac is indicated for the treatment of hypertension and chronic stable angina.
How does Tiazac compare to other diltiazem formulations?
Tiazac has different pharmacokinetic profiles compared to other diltiazem formulations like Cardizem CD, with higher Cmax and AUC after single doses but similar values at steady-state[4].
What are the common adverse reactions of Tiazac?
Common adverse reactions include first-degree AV block, dizziness, and headache. Serious adverse reactions are rare but can include exacerbation of heart failure in patients with impaired ventricular function[1].
Why was the FTC involved in the development of Tiazac?
The FTC was involved to ensure competition in the diltiazem market, addressing concerns about Hoechst AG's merger with MMD and Biovail's actions to block generic competition[2][5].
Are generic versions of Tiazac available?
Generic versions of Tiazac are anticipated but not yet widely available. Different sustained-release mechanisms may affect their market dynamics[3].
Cited Sources
- Tiazac (diltiazem hydrochloride) Extended-Release Capsules USP Label.
- Federal Trade Commission: Hoechst AG.
- Drugs & Therapy - SHANDS.
- Relative bioavailability of Cardizem CD and Tiazac controlled-release diltiazem.
- Federal Trade Commission: Biovail Corporation.
