CARDIZEM LA

Diltiazem is well absorbed from the gastrointestinal tract and is subject to an extensive first-pass effect, giving an absolute bioavailability (compared to intravenous administration) of about 40%. Diltiazem undergoes extensive metabolism in which only 2% to 4% of the unchanged drug appears in the urine. Drugs that induce or inhibit hepatic microsomal enzymes may alter diltiazem disposition. Total radioactivity measurement following short IV administration in healthy volunteers suggests the pre...

14.1 Hypertension In a randomized, double-blind, parallel-group, dose-response study involving 478 patients with essential hypertension, evening doses of CARDIZEM LA 120, 240, 360, and 540 mg were compared to placebo and to 360 mg administered in the morning. The mean reductions in diastolic blood pressure by ABPM at roughly 24 hours after the morning (4 AM to 8 AM) or evening (6 PM to 10 PM) administration (i.e., the time corresponding to expected trough serum concentrations) are shown in the table below: Mean Change in Trough Diastolic Pressure by ABPM Evening Dosing Morning Dosing 120 mg 24...

The following adverse reactions are described in greater detail, in other sections:

• Bradycardia and AV block [see Warnings and Precautions ( 5.1 )]
• Heart failure [see Warnings and Precautions ( 5.2 )]
• Acute hepatic injury [see Warnings and Precautions ( 5.3 )]
• Severe skin reactions [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (>2%) are lower limb edema, sinus congestion and rash in patients treated for hypertension, and lower limb edema, headache, dizziness, f...

CARDIZEM LA is contraindicated in:

• Patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker.
• Patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker.
• Patients with hypotension (less than 90 mm Hg systolic).
• Patients who have demonstrated hypersensitivity to the drug.
• Patients with acute myocardial...

• Bradycardia, second- or third-degree AV block: Monitor heart rate and rhythm. ( 5.1 )
• Heart failure: Monitor for signs and symptoms. ( 5.2 )
• Increased liver enzymes and acute hepatic injury. ( 5.3 )
• Severe skin reactions. ( 5.4 ) 5.1 Bradycardia or AV Block CARDIZEM LA may cause abnormally slow heart rates or second- or third-degree AV block. Patients with sick sinus syndrome are at increased risk of bradycardia. Concomitant use of diltiazem with beta-blockers or digitalis may result in ...

7 DRUG INTERACTIONS

• Beta-blockers, digitalis, and other agents known to impair cardiac contractility and conduction may increase risk for hypotension, bradycardia, and heart failure. ( 7.1 )
• CYP450 3A4: Diltiazem is both a substrate and inhibitor of CYP450 3A4. CYP450 3A4 substrates may require dosage adjustment. ( 7.2 ) 7.1 Agents Known to Impair Cardiac Contractility and Conduction Using oth...