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Diltiazem Hydrochloride

Pronunciation

Pronunciation: dill-TIE-uh-zem HIGH-droe-KLOR-ide
Class: Calcium channel blocking agent

Trade Names

Cardizem
- Tablets 30 mg
- Tablets 60 mg
- Tablets 90 mg
- Tablets 120 mg
- Powder for injection 25 mg
- Injection 5 mg/mL

Cardizem CD
- Capsules, ER 120 mg
- Capsules, ER 180 mg
- Capsules, ER 240 mg
- Capsules, ER 300 mg
- Capsules, ER 360 mg

Cardizem LA
- Tablets, ER 120 mg
- Tablets, ER 180 mg
- Tablets, ER 240 mg
- Tablets, ER 300 mg
- Tablets, ER 360 mg
- Tablets, ER 420 mg

Cartia XT
- Capsules, ER 120 mg
- Capsules, ER 180 mg
- Capsules, ER 240 mg
- Capsules, ER 300 mg

Dilacor XR
- Capsules, ER 120 mg
- Capsules, ER 180 mg
- Capsules, ER 240 mg

Dilt-XR
- Capsules, ER 120 mg
- Capsules, ER 180 mg
- Capsules, ER 240 mg

Diltia XT
- Capsules, ER 180 mg

Diltiazem Hydrochloride Extended Release
- Capsules, ER 60 mg
- Capsules, ER 90 mg

Diltzac
- Capsules, ER 120 mg
- Capsules, ER 180 mg
- Capsules, ER 240 mg
- Capsules, ER 300 mg
- Capsules, ER 360 mg

Matzim LA
- Tablets, ER 120 mg
- Tablets, ER 180 mg
- Tablets, ER 240 mg
- Tablets, ER 300 mg
- Tablets, ER 360 mg
- Tablets, ER 420 mg

Taztia XT
- Capsules, ER 120 mg
- Capsules, ER 180 mg
- Capsules, ER 240 mg

Tiazac
- Capsules, ER 120 mg
- Capsules, ER 180 mg
- Capsules, ER 240 mg
- Capsules, ER 300 mg
- Capsules, ER 360 mg
- Capsules, ER 420 mg

Apo-Diltiaz (Canada)
Apo-Diltiaz CD (Canada)
Apo-Diltiaz Injectable (Canada)
Apo-Diltiaz SR (Canada)
Gen-Diltiazem (Canada)
Gen-Diltiazem CD (Canada)
Novo-Diltiazem (Canada)
Novo-Diltiazem CD (Canada)
Nu-Diltiaz (Canada)
Nu-Diltiaz-CD (Canada)
ratio-Diltiazem CD (Canada)
Sandoz Diltiazem CD (Canada)
Tiazac XC (Canada)

Pharmacology

Inhibits movement of calcium ions across the cell membrane in systemic and coronary vascular smooth muscle; slows calcium ion movement across cell membranes in both cardiac muscle and cardiac pacemaker cells, decreasing sinoatrial and atrioventricular (AV) conduction.

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Pharmacokinetics

Absorption

IV

T max is 2 to 3 h.

Extended release (ER)

T max is 10 to 14 h.

Immediate release (IR)

T max is 2 to 4 h.

Distribution

Vd approximately 305 L. 70% to 80% protein bound (approximately 40% to alpha l -acid glycoprotein and approximately 30% to albumin). Excreted in breast milk.

Metabolism

Metabolized in the liver (including via CYP-450) to several metabolites; desacetyl diltiazem is 25% to 50% as potent as diltiazem. Undergoes first-pass metabolism after oral administration.

Elimination

The half-life is approximately 3.4 h (IV), 4 to 9 h (ER), and 3 to 4.5 h (IR). 2% to 4% is excreted unchanged in the urine (oral). Systemic Cl is approximately 65 L/h (IV).

Peak

2 to 5 min (IV); 11 to 18 h (ER).

Special Populations

Renal Function Impairment

No difference in the pharmacokinetic profile of diltiazem in patients with severely impaired renal function.

Hepatic Function Impairment

Bioavailability is increased, and half-life is prolonged.

Indications and Usage

Oral

Treatment of angina pectoris caused by coronary artery spasm; chronic stable angina (classic effort-associated angina); essential hypertension (ER and sustained-release forms only).

Parenteral

Treatment of atrial fibrillation or flutter; paroxysmal supraventricular tachycardia.

Contraindications

Sick sinus syndrome or second- or third-degree AV block, except with functioning pacemaker; hypotension with systolic pressure less than 90 mm Hg; acute MI; pulmonary congestion; hypersensitivity to the drug; ventricular tachycardia (IV); atrial fibrillation or atrial flutter associated with an accessory bypass tract (IV); IV diltiazem and IV beta-blockers administered together (within a few hours).

Dosage and Administration

Dosage regimens should be individualized.

Angina
Adults Cardizem

PO Start with 30 mg 4 times daily before meals and at bedtime. Gradually increase dosage at 1- to 2-day intervals until optimum response (average optimum dose range 180 to 360 mg/day).

Cardizem CD and Cartia XT

PO Start with 120 to 180 mg once daily. Some patients may respond to doses up to 480 mg once daily. When necessary, titrate the dose over 7 to 14 days.

Cardizem LA and Matzim LA

PO Start with 180 mg once daily. Some patients may respond to doses up to 360 mg once daily. Titrate dose over 7 to 14 days.

Dilacor XR and Diltia XT

PO Start with 120 mg once daily. Some patients may respond to doses up to 480 mg once daily. When necessary, titrate the dose over 7 to 14 days.

Diltzac and Tiazac

PO Start with 120 to 180 mg once daily. Some patients may respond to doses up to 540 mg once daily. When necessary, titrate the dose over 7 to 14 days.

Atrial Fibrillation/Flutter/Paroxysmal Supraventricular Tachycardia
Adults Direct IV single bolus injection

Parenteral Initial dose is 0.25 mg/kg as a bolus administered over 2 min (reasonable dose is 20 mg for average patient). If response is inadequate after 15 min, administer as a second 0.35 mg/kg over 2 min (reasonable dose is 25 mg for average patient). Individualize subsequent IV doses. Dose low body weight patients on a mg/kg basis. Although the duration of action may be shorter, some patients may respond to an initial dose of 0.15 mg/kg.

Continuous IV infusion

Parenteral For continued reduction of heart rate (up to 24 h) in patients with atrial fibrillation or atrial flutter, IV infusion may be administered. Immediately following administration of a bolus dose of 20 mg (0.25 mg/kg) or 25 mg (0.35 mg/kg) and reduction of heart rate, begin an IV infusion. The recommended initial infusion rate is 10 mg/h; however, some patients may maintain response to an initial rate of 5 mg/h. The infusion rate may be increased in 5 mg/h increments up to 15 mg/h as needed, if further reduction in heart rate is necessary. The infusion may be maintained for up to 24 h (max, 24 h and 15 mg/h).

Hypertension
Adults Extended-release capsules

PO Start with 60 to 120 mg twice daily or 180 to 240 mg once daily. Max antihypertensive effect usually occurs by 14 days of chronic therapy (optimum dose range 240 to 360 mg once daily, but some patients respond to lower doses or higher doses up to 480 mg once daily).

Cardizem CD and Cartia XT

PO 180 to 240 mg once daily; however, some patients may respond to lower doses. Maximum effect is usually achieved by 14 days of chronic therapy. Usual range is 240 to 360 mg once daily. Some patients may respond to doses up to 480 mg once daily.

Cardizem LA and Matzim LA

PO Start with 180 to 240 mg once daily; however, some patients may respond to lower doses. Max effect is usually achieved by 14 days of chronic therapy. Dose range studied in clinical trials was 120 to 540 mg once daily (max, 540 mg daily).

Dilacor XR and Diltia XT

PO 180 to 240 mg once daily (usual dose range, 180 to 480 mg once daily). Individual patients, particularly those 60 yr of age and older, may respond to lower doses of 120 mg once daily. Some patients may require doses up to 540 mg once daily.

Diltzac and Tiazac

PO Start with 120 to 240 mg once daily. Max effect is usually achieved by 14 days of chronic therapy. Usual dose range is 120 to 540 mg once daily.

General Advice

  • May be used alone or in combination with other CV medications for the treatment of hypertension and angina.
  • Swallow tablets and capsules whole. Do not crush, chew, or break.
  • Diltzac capsules may be opened and contents sprinkled onto a spoonful of applesauce. Swallow applesauce immediately without chewing, and follow with a glass of cool water.
  • For administration by IV bolus or infusion only.
  • For IV infusion, add prescribed dose to prescribed volume of sodium chloride 0.9%, dextrose 5% in water, or dextrose 5% in sodium chloride 0.45% following manufacturer's dilution charts.

Storage/Stability

Store tablets and capsules at controlled room temperature (59° to 86°F). Protect from moisture and avoid excessive humidity. Discard any unused solution. Do not save for future use. Store vials for injection in refrigerator (36° to 46°F). May store vials for injection at room temperature for up to 1 mo, but any unused injection must be destroyed after 1 mo. Store syringes and vials of powder for injection at room temperature (59° to 86°F). Do not freeze. Use reconstituted solution immediately or store for up to 24 h at controlled room temperature.

Drug Interactions

Anesthetics

Depression of cardiac contractility, conductivity, and automaticity as well as vascular dilation associated with anesthetics may be potentiated.

Benzodiazepines (eg, midazolam, triazolam), buspirone, carbamazepine, cyclosporine, digitalis, lovastatin, quinidine, simvastatin

Plasma levels of these agents may be elevated by diltiazem, increasing the pharmacologic and toxic effects. The dose of simvastatin should not exceed 10 mg/day.

Beta-blockers (eg, propanolol)

May have additive negative inotropic and chronotropic effects. Use with caution.

Cimetidine, ranitidine

Diltiazem levels may be increased.

Other antihypertensive agents

May have additive effects.

Rifampin

Coadministration lowered diltiazem plasma concentrations to undetectable levels. Avoid coadministration.

Incompatibility

Do not mix with furosemide.

Adverse Reactions

Cardiovascular

Bradycardia (4%); first-degree AV block (3%); angina, arrhythmia, AV block (second- or third-degree), bundle branch block, CHF, ECG abnormalities, hypotension, palpitations, syncope, tachycardia, ventricular extrasystoles (less than 2%); peripheral edema, asystole, MI (postmarketing).

CNS

Dizziness (6%); headache, fatigue (5%); asthenia (3%); abnormal dreams, amnesia, asthenia, depression, gait abnormalities, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tremor (less than 2%); extrapyramidal symptoms, lightheadedness, weakness, shakiness (postmarketing).

Dermatologic

Rash (2%); ecchymosis, petechiae, photosensitivity, pruritus (less than 2%); alopecia, erythema multiforme (including Stevens-Johnson syndrome and TEN), exfoliative dermatitis, purpura, generalized rash (postmarketing).

EENT

Sinus congestion (2%); amblyopia, epistaxis, eye irritation, nasal congestion, rhinitis, tinnitus (less than 2%); retinopathy (postmarketing).

GI

Nausea (1%); anorexia, constipation, diarrhea, dry mouth, dysgeusia, thirst, vomiting (less than 2%); abdominal discomfort, cramps, dyspepsia, gingival hyperplasia (postmarketing).

Genitourinary

Albuminuria, crystalluria, hyperuricemia, impotence, nocturia, polyuria, sexual difficulties, gynecomastia (less than 2%).

Hematologic-Lymphatic

Hemolytic anemia, increased bleeding time, leukopenia, thrombocytopenia (postmarketing).

Lab Tests

Mild elevations of ALT, AST, LDH, and alkaline phosphatase, CPK increase (less than 2%).

Metabolic-Nutritional

Hyperglycemia, weight gain (less than 2%).

Musculoskeletal

Muscle cramps, neck rigidity, osteoarticular pain (less than 2%); joint pain.

Respiratory

Cough (2%); dyspnea (less than 2%).

Miscellaneous

Lower limb edema (8%); edema (5%); flushing (1%); allergic reactions, pain (less than 2%); angioedema (postmarketing).

Precautions

Monitor

Monitor and record BP and pulse frequently during treatment. Continuously monitor ECG during administration. Monitor renal and hepatic function regularly.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Use with caution. Dosage may need to be decreased.

Hepatic Function

Use with caution. Dosage may need to be decreased.

Acute hepatic injury

Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed. These elevations were usually transient and often resolved with continued treatment.

Cardiac conduction

Prolongs AV node refractory periods without prolonging sinus node recovery time, except in patients with sick sinus syndrome. This may rarely cause abnormally slow heart rates, particularly in patients with sick sinus syndrome, or second- or third-degree AV block.

CHF

Use with caution. Worsening of CHF has been reported.

Dermatological effects

Skin eruptions, progressing to erythema multiforme and/or exfoliative dermatitis, have been reported.

Hypotension

May occur.

Withdrawal syndrome

Abrupt withdrawal may cause increased frequency and duration of angina. Dosage is tapered gradually.

Overdosage

Symptoms

Bradycardia, hypotension, high-degree AV block, heart failure.

Patient Information

  • Advise patient or caregiver that IV diltiazem will be prepared and administered by health care professionals in a medical setting.
  • Advise patient that dose of medication may be adjusted to obtain max benefit.
  • Advise patient taking IR tablets to take 3 or 4 times daily as prescribed. Advise patient to take each dose without regard to meals, but to take with food if stomach upset occurs.
  • Advise patient taking ER products to take once daily as prescribed, without regard to meals. Advise patient to take with food if stomach upset occurs.
  • Caution patient to swallow ER products whole and not to crush or chew.
  • Advise patient to try to take each dose at about the same time each day.
  • Inform patient that drug controls, but does not cure, hypertension or angina, and to continue taking as prescribed even when BP is not elevated or angina symptoms are not present.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Instruct patient to continue taking other BP or angina medications as prescribed by health care provider.
  • Instruct patient being treated for angina to notify health care provider if frequency or severity of chest pain or need for sublingual nitroglycerin appears to be increasing.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
  • Advise patients to notify their health care provider if any of the following occur: frequent episodes of dizziness when arising; slow heart beat; persistent fatigue; any other unusual or unexplained symptom or sign.
  • Emphasize to hypertensive patient importance of other modalities on BP: weight control, regular exercise, smoking cessation, moderate intake of alcohol and salt.

Copyright © 2009 Wolters Kluwer Health.

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