Generic Name: diltiazem

Uses

Angina

Used in the management of Prinzmetal variant angina and chronic stable angina pectoris.

Calcium channel blockers considered the drugs of choice in management of Prinzmetal variant angina.

Appears to be as effective as β-adrenergic blocking agents (e.g., propranolol) and/or oral nitrates in the management of chronic stable angina pectoris; however, generally should be used only when the patient cannot tolerate adequate doses of or is refractory to these drugs.

Management of unstable angina† in patients who have continuing or ongoing ischemia when therapy with β-blocking agents and nitrates is inadequate, not tolerated, or contraindicated and when severe left ventricular dysfunction, pulmonary edema, or other contraindications are not present.

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).

Only extended-release formulations currently are recommended for management of hypertension.

One of several preferred initial therapies for hypertensive patients with a high risk of developing coronary artery disease, including those with diabetes mellitus.

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred for monotherapy by JNC 7.

Supraventricular Tachyarrhythmias

Management of supraventricular tachyarrhythmias, including rapid conversion to sinus rhythm of paroxysmal supraventricular tachycardias (PSVT) (e.g., those associated with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome) and temporary control of rapid ventricular rate in atrial flutter or fibrillation.

One of several preferred antiarrhythmic agents for the treatment of stable, narrow-complex supraventricular tachycardias (e.g., paroxysmal supraventricular tachycardia [reentry supraventricular tachycardia], ectopic or multifocal atrial tachycardia†, junctional tachycardia†) if the rhythm is not controlled by vagal maneuvers or adenosine and to control the ventricular response rate in atrial fibrillation or flutter.

AMI

Calcium-channel blocking agents have not proved beneficial in the early treatment or secondary prevention of AMI† and the possibility that they may be harmful has been raised.

May be used for relief of ongoing ischemia or to control rapid ventricular response with atrial fibrillation after an AMI† when β-adrenergic blocking agents are ineffective or contraindicated, but only in patients in whom there is no evidence of CHF, left-ventricular dysfunction, or AV block and only after weighing carefully the potential benefits versus risks, particularly negative inotropic effects and concerns about short-acting formulations of the drugs.

Hyperthyroidism

Short-term adjunctive therapy in the treatment of tachycardia and tachyarrhythmias in patients with hyperthyroidism† and/or thyrotoxicosis† in whom therapy with β-adrenergic blocking agents is contraindicated or not tolerated.

Dosage and Administration

Administration

Administer by direct IV injection, continuous IV infusion, or orally.

Oral Administration

Conventional Tablets

Administer tablets orally 3–4 times daily before meals and at bedtime.

Extended-release Capsules

Administer orally; directions for administration (e.g., frequency, whether to administer with or without food, potential for opening capsules and mixing with food) may vary by manufacturer and formulation; consult specific manufacturer's information for additional information.

Cardizem^® CD, Dilacor XR^®, Dilt-XR^®, Tiazac^®, Taztia XT^®, Cartia XT^®, or Diltia XT^® may be administered once daily; diltiazem hydrochloride extended-release capsules (12 hours) are administered twice daily.

Cardizem^® CD and Cartia XT^® may be administered without regard to meals. However, Dilacor XR^®, Diltia XT^®, and Dilt-XR^® should be taken on an empty stomach, swallowed whole and not opened, chewed, or crushed.

Tiazac^® and Taztia XT^® may be opened and the entire contents sprinkled on a small amount of applesauce (not hot) immediately prior to administration; subdividing the contents of capsules is not recommended. Swallow the entire mixture without chewing. Immediately drink a glass of cool water to ensure that all of the mixture is swallowed. Do not store the sprinkle/food mixture for use at a later time.

Extended-release Tablets

Administer orally once daily without regard to meals. Tablet should be swallowed whole and not chewed or crushed.

IV Injection

Monitor ECG and BP continuously during IV administration.

Reconstitution

Prepare solutions from the powder for injection (Lyo-Ject^®) according to the manufacturer's directions.

Dilution

Injection solutions containing 5 mg/mL or powder for injection that has been reconstituted according to manufacturer's directions may be administered by direct IV injection without any further dilution.

Rate of Administration

Administer over 2 minutes.

IV Infusion

Reconstitution

Prepare solutions from the powder for injection (Lyo-Ject^®) according to the manufacturer's directions.

Dilution

Dilute 5 mg/mL injection solution or reconstituted powder for injection in the appropriate volume of a compatible infusion solution (i.e., 0.9% sodium chloride, 5% dextrose, or 5% dextrose and 0.45% sodium chloride) to produce a final diltiazem hydrochloride concentration of 1, 0.83, or 0.45 mg/mL, respectively.

Rate of Administration

Usually 10 mg/hour; however, may range from 5–15 mg/hour.

Dosage

Available as diltiazem hydrochloride; dosage expressed in terms of the salt.

Adults

Prinzmetal Variant Angina

Conventional Tablets

Oral

Initially, 30 mg 4 times daily. Increase gradually at 1- to 2-day intervals until optimum control is obtained. Usual maintenance dosage is 180–360 mg daily. After manifestations are controlled, reduce dosage to lowest level that will maintain relief of symptoms.

Extended-release Capsules

Oral

Initially, 120 or 180 mg once daily when administered as extended-release capsules (Cardizem^® CD, Cartia XT^®). Individualize dosage based on response; titrate dosage increases over 7–14 days. Some patients may respond to higher dosages of up to 480 mg once daily.

Chronic Stable Angina

Conventional Tablets

Oral

Initially, 30 mg 4 times daily. Increase gradually at 1- to 2-day intervals until optimum control is obtained. Usual maintenance dosage is 180–360 mg daily. After manifestations are controlled, reduce dosage to lowest level that will maintain relief of symptoms.

Extended-release Capsules

Oral

Initially, 120 (Dilacor XR^®, Diltia XT^®, Dilt-XR^®) or 120–180 mg (Cardizem^® CD, Cartia XT^®, Tiazac^®, Taztia XT^®) once daily when administered as extended-release capsules. Individualize dosage based on response; titrate dosage increases over 7–14 days. Some patients may respond to higher dosages of up to 480 (Cardizem^® CD, Cartia XT^®, Dilacor XR^®, Diltia XT^®, Dilt-XR^®) to 540 mg (Tiazac^®, Taztia XT^®) once daily.

Extended-release Tablets

Oral

Initially, 180 mg once daily when administered as extended-release tablets (Cardizem^® LA). Individualize dosage based on response; titrate dosage increases over 7–14 days. Some patients may respond to higher dosages of up to 360 mg once daily.

Hypertension

Extended-release Capsules

Oral

Maximum hypotensive effect associated with a given dosage level usually is observed within 14 days.

Switching to Cardizem^® CD Extended-release Capsules

Oral

Patients whose BP is adequately controlled with diltiazem therapy (as tablets or other extended-release capsules) alone or in combination with another antihypertensive agent may be safely switched to Cardizem^® CD or Cartia XT^® extended-release capsules or Cardizem^® LA extended-release tablets at the nearest equivalent daily dosage. Subsequent titration of dosage is based on the clinical response of the patient.

Conventional Tablets

Oral

Initially, 30 mg 3 times daily; may be increased to a maximum dosage of 360 mg daily given in 3 or 4 divided doses.†

Extended-release Tablets

Oral

Initially, 180–240 mg daily; however, some patients may respond to a lower dosage. Individualize dosage based on response; maximum hypotensive effect associated with a given dosage level usually is observed within 14 days. Usual maintenance dosage is 120–540 mg daily; however, JNC 7 recommends a usual maximum dosage of 420 mg daily.

Supraventricular Tachyarrhythmias

Paroxysmal Supraventricular Tachycardia, Junctional Tachycardia, Ectopic Tachycardia, Multifocal Atrial Tachycardia)

IV

Initially, 15–20 mg (or 0.25 mg/kg) by direct IV injection over 2 minutes. If response is inadequate (i.e., conversion to normal sinus rhythm does not occur) give a second dose of 20–25 mg (or 0.35 mg/kg) 15 minutes after the initial dose.†

Maintenance infusion: 5–15 mg/hour; titrate dose to heart rate.†

Patients with low body weights should be dosed on a mg/kg basis.†

Ventricular Rate Control in Atrial Fibrillation and Flutter

IV

Initially, 15–20 mg (or 0.25 mg/kg) by direct IV injection over 2 minutes. If response is inadequate, give 20–25 mg (or 0.35 mg/kg) 15 minutes after the initial dose.

Maintenance infusion: 5–15 mg/hour; titrate dose to heart rate.

Prescribing Limits

Adults

Angina

Oral

Cardizem^® LA extended-release tablets: Maximum 360 mg daily.

Cardizem^® CD, Dilacor XR^®, Diltia XT^®, Dilt-XR^®, and Cartia XT^® extended-release capsules: Maximum 480 mg daily.

Tiazac^® and Taztia XT^® extended-release capsules: Maximum 540 mg daily.

Hypertension

Oral

Cardizem^® conventional tablets†: Maximum 360 mg daily.

Cardizem^® CD and Cartia XT^® extended release capsules: Maximum 480 mg daily.

Dilt-XR^®, Dilacor XR^®, Diltia XT^®, Taztia XT^®, and Tiazac^® extended-release capsules and Cardizem^® LA extended-release tablets: maximum 540 mg daily.

However, JNC 7 recommends a usual maximum dosage of 420 mg daily for these preparations.

Supraventricular Tachyarrhythmias

IV

Maintenance infusion: Maximum 15 mg/hour for ≤24 hours.

Special Populations

Hepatic Impairment

Supraventricular Tachyarrhythmias

Atrial Fibrillation and Flutter

IV

Maintenance infusion: Dosage requirements may be lower.

Geriatric Patients

Angina

Select dosage cautiously; geriatric patients may respond to lower dosages.

Hypertension

Select dosage cautiously. The manufacturers of Dilacor XR^®, Dilt-XR^®, and Diltia XT^® state that patients 60 years of age or older may respond to an initial daily dosage of 120 mg.

Atrial Fibrillation and Flutter

Maintenance IV infusion: Dosage requirements may be lower.

Cautions

Contraindications

• Contraindicated in patients with known hypersensitivity to the drug.
• Sick sinus syndrome (unless a functioning ventricular pacemaker is in place).
• Second- or third-degree AV block (unless a functioning ventricular pacemaker is in place).
• Severe hypotension (SBP <90 mm Hg).
• Oral preparations contraindicated in patients with AMI with radiographically documented pulmonary congestion.
• IV diltiazem contraindicated in patients with cardiogenic shock.
• IV diltiazem contraindicated in patients with VT.
• IV diltiazem contraindicated in patients with atrial flutter or fibrillation with an accessory pathway (e.g., those with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome).
• IV diltiazem contraindicated if concurrent or recent (e.g., within a few hours) administration of IV β-adrenergic blockers.

Warnings/Precautions

Warnings

Cardiac Conduction

Potential for abnormally slow heart rate (particularly in patients with sick sinus syndrome) or second- or third-degree AV block.

Additive effects on cardiac conduction (e.g., prolonging AV node conduction) possible with concomitant use of diltiazem with β-adrenergic blocking agents or digoxin.

If high-degree AV block occurs in patients with sinus rhythm receiving IV diltiazem, discontinue the drug and institute appropriate supportive measures.

CHF

Risk of CHF, especially in those with preexisting ventricular impairment; limited experience in patients with impaired ventricular function receiving concomitant β-adrenergic blocking agents. Use with caution.

Hypotension

Possible symptomatic hypotension.

Acute Hepatic Injury

Substantial elevations in hepatic function test results (e.g., serum AST [SGOT], ALT [SGPT], LDH, alkaline phosphatase) and phenomena associated with hepatocellular injury rarely reported. Usually occurs early in therapy (e.g., 1–8 weeks); reversible upon discontinuation of therapy.

Ventricular Premature Beats

With IV administration, possible transient VPB on conversion of PSVT to sinus rhythm; appear to be benign and of little clinical importance.

Sensitivity Reactions

Possible diltiazem-induced skin eruptions with oral preparations; may infrequently progress to severe dermatologic reactions (e.g., erythema multiforme, exfoliative dermatitis). If effects persist during therapy, the drug should be discontinued. Potential for occurrence with IV administration.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk; discontinue nursing.

Pediatric Use

Safety and efficacy not established.

Injection in single-use (Lyo-Ject) syringes contains benzyl alcohol as a preservative and should not be used in neonates.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Hepatic Impairment

Use with caution.

Renal Impairment

Use with caution.

Common Adverse Effects

With oral therapy, edema, headache, dizziness, asthenia, first-degree AV block.

With IV therapy, hypotension, injection site reactions, vasodilation, arrhythmia.

Interactions

Metabolized principally by CYP3A4. Inhibits CYP3A4.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors, inducers, and substrates of CYP3A4: potential pharmacokinetic interaction (altered plasma diltiazem concentrations).

Drugs Metabolized by Microsomal Enzymes

Potential pharmacokinetic interaction: altered bioavailability and/or clearance of drugs metabolized by CYP3A4.

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Following oral administration of conventional tablets, approximately 80% of a dose is rapidly absorbed from the GI tract.

Absolute bioavailability is about 40%; undergoes extensive first-pass metabolism.

Onset

Following direct IV injection, reductions in heart rate usually occur within 3 minutes and hemodynamic effects (e.g., decrease in BP) generally occur within 2 minutes; effects on the AV node generally occur within minutes following initiation of a continuous IV infusion.

Duration

Following direct IV injection, reductions in heart rate generally persist for 1–3 hours; blood pressure reductions following direct IV injection generally are short-lived but may last 1–3 hours. Effects on the AV node may persist for 0.5–10 hours following a continuous IV infusion.

Food

Rate of absorption may be increased if Tiazac^® extended-release capsules are taken with a high-fat meal. Food may affect the extent of absorption of some extended-release capsules (Dilacor XR^®, Diltia XT^®).

Distribution

Extent

Rapidly and extensively distributed into body tissues.

Distributed into milk, in concentrations approximately equal to maternal serum concentrations.

Plasma Protein Binding

About 70–85% is bound to plasma proteins, but only 30–40% is bound to albumin.

Elimination

Metabolism

Rapidly and almost completely metabolized in the liver to several active and at least 5 inactive metabolites principally via CYP enzyme system, mainly CYP3A4.

Elimination Route

Excreted principally in urine as metabolites, with approximately 2–4% of a dose excreted unchanged.

Half-life

2–11 hours.

Special Populations

In geriatric patients, plasma half-life of the drug may be increased.

In patients with severe renal impairment, pharmacokinetics were unchanged.

Oral clearance may be reduced and half-life prolonged in patients with liver cirrhosis.

Stability

Storage

Oral

Conventional Tablets

Tight containers at 25°C (may be exposed to 15–30°C).

Protect from excessive humidity.

Extended-release Capsules

25°C (may be exposed to 15–30°C).

Protect from excessive humidity.

Extended-release Tablets

Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).

Protect from excessive humidity.

Parenteral

Powder for Injection

15–30°C. Do not freeze.

Store reconstituted product at 15–30°C; discard 24 hours after reconstitution. Discard unused portion.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Drug Compatibility

Actions

• Inhibits transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations.
• Peripheral arterial vasodilator; acts directly on vascular smooth muscle causing reduction in peripheral vascular resistance (afterload) and BP.
• Substantial inhibitory effects on the cardiac conduction system, acting principally at the atrioventricular (AV) node to slow conduction time and prolong AV nodal refractoriness.

Advice to Patients

• Importance of swallowing extended-release tablets whole; do not chew, crush, or break.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions August 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.