Cardizem La

— THERAPEUTIC CATEGORIES —
  • Angina
  • Hypertension
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Cardizem La Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Diltiazem HCl 120mg, 180mg, 240mg, 300mg, 360mg, 420mg; ext-rel tabs.

    Pharmacological Class

    Calcium channel blocker (CCB) (benzothiazepine).

    See Also

    How Supplied

    LA tabs—30, 90; CD 120mg, 180mg, 240mg, 300mg—30, 90; CD 360mg—90; Tabs 30mg—100, 500; 60mg, 90mg, 120mg—100

    How Supplied

    Cardizem® LA Extended-Release Tablets

    • Cardizem® LA is supplied as capsule shaped, white film-coated tablets, debossed with “B” on one side and the diltiazem content (mg) on the other side in the following strengths: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg.

    • Cardizem LA is supplied in 30- and 90-count bottles for all dosage strengths.

    Storage

    • Storage conditions: Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Avoid excessive humidity and temperatures above 30°C (86°F).

    Manufacturer

    Bausch Health Companies Inc.

    Mechanism of Action

    The therapeutic effects of diltiazem are believed to be related to its ability to inhibit the cellular influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle. Diltiazem has been shown to increase exercise tolerance, probably due to its ability to reduce myocardial oxygen demand. It has shown to be a potent dilator of coronary arteries, both epicardial and subendocardial.

    Cardizem La Indications

    Indications

    Chronic stable angina.

    Cardizem La Dosage and Administration

    Adult

    Swallow whole; take at the same time each day (AM or PM). Initially 180mg once daily; adjust at 1–2 week intervals up to 360mg/day. Concomitant simvastatin: max 240mg/day.

    Children

    Not established.

    Cardizem La Contraindications

    Contraindications

    Sick sinus syndrome, 2nd- or 3rd-degree AV block unless paced. Hypotension. Acute MI and pulmonary congestion documented by X-ray on admission.

    Cardizem La Boxed Warnings

    Not Applicable

    Cardizem La Warnings/Precautions

    Warnings/Precautions

    CHF. Renal or hepatic impairment (monitor). Discontinue if persistent rash occurs. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

    Warnings/Precautions

    Bradycardia or AV Block

    • 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 additive effects on cardiac conduction.

    Heart Failure (HF)

    • Patients with preexisting impairment of ventricular function may develop worsening of CHF.

    • Use caution when using in combination with beta-blockers among patients with impaired ventricular function.

    Acute Hepatic Injury

    • Significant elevations in liver enzymes such as alkaline phosphatase, LDH, AST (SGOT), ALT (SGPT) and signs of acute hepatic injury have been reported with diltiazem therapy. 

    • Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed in clinical studies.

    • These reactions have been transient and frequently resolved even with continued diltiazem treatment. Moreover, the reactions have typically occurred early after initiating treatment and were reversible with discontinuation of therapy.

    Severe Skin Reactions

    • Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and/or exfoliative dermatitis have been reported.

    Pregnancy Considerations

    • No well-controlled studies in pregnant women. Use diltiazem in pregnant women only if the potential benefit justifies the potential risk to the fetus.

    Nursing Mother Considerations

    • Diltiazem is excreted in human milk.

    • Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or diltiazem.

    Pediatric Considerations

    • Safety and efficacy in pediatric patients have not been established.

    Geriatric Considerations

    • Use caution in elderly patients and select dose starting at the low end of the range due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    Cardizem La Pharmacokinetics

    Absorption

    • Peak plasma levels of Cardizem LA 360 mg are reached between 11 and 18 hours.

    Distribution

    • 70–80% plasma protein bound.

    Metabolism

    Hepatic.

    Elimination

    Renal. Half-life: 6–9hrs.

    Cardizem La Interactions

    Interactions

    Concomitant ivabradine, rifampin, alcohol: avoid. Caution with digoxin, β-blockers, others that may affect cardiac conduction (may lead to AV block). Monitor heart rate with concomitant clonidine. Potentiates propranolol, benzodiazepines, buspirone, cyclosporine, carbamazepine, quinidine, lovastatin, simvastatin (limit to max 10mg/day); monitor. Caution with CYP3A4 substrates, inhibitors (eg, cimetidine), or inducers. Anesthetics may potentiate cardiac depression.

    Cardizem La Adverse Reactions

    Adverse Reactions

    Edema, headache, fatigue, dizziness, asthenia, 1st-degree AV block, bradycardia, rash (may be serious); rare: hypotension, liver abnormalities.

    Adverse Reactions

    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, fatigue, bradycardia, first-degree AV block and cough in patients treated for angina. 

    The following events were reported infrequently (<1%) in angina or hypertension trials:

    • Cardiovascular: Angina, bundle branch block, palpitations, syncope, tachycardia, ventricular extrasystoles. 

    • Nervous System: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tinnitus, tremor.

    • Gastrointestinal: Anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, thirst, vomiting, weight increase.

    • Dermatological: Petechiae, photosensitivity, pruritus, urticaria.  

    • Other: Amblyopia, CPK increase, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties.

    Cardizem La Clinical Trials

    Clinical Trials

    Angina

    • In a randomized, double-blind, parallel-group, dose-response trial, the efficacy of Cardizem LA was evaluated in 311 patients with chronic stable angina. Patients were randomly assigned to receive evening doses of either placebo or Cardizem LA 180 mg, 360 mg, and 420 mg, or a morning dose of Cardizem LA 360 mg.

    • All doses of Cardizem LA administered at night increased exercise tolerance when compared with placebo after 21 hours. The mean effect, placebo-subtracted, was 20 to 28 seconds for all three doses, and no dose-response was demonstrated. 

    • Cardizem LA 360 mg given in the morning, also improved exercise tolerance when measured 25 hours later. 

    • Cardizem LA had a larger effect to increase exercise tolerance at peak serum concentrations than at trough.

    Cardizem La Note

    Not Applicable

    Cardizem La Patient Counseling

    See Literature

    Cardizem La Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Diltiazem HCl 120mg, 180mg, 240mg, 300mg, 360mg, 420mg; ext-rel tabs.

    Pharmacological Class

    Calcium channel blocker (CCB) (benzothiazepine).

    See Also

    How Supplied

    LA tabs—30, 90; CD 120mg, 180mg, 240mg, 300mg—30, 90; CD 360mg—90

    How Supplied

    Cardizem® LA Extended-Release Tablets

    • Cardizem® LA is supplied as capsule shaped, white film-coated tablets, debossed with “B” on one side and the diltiazem content (mg) on the other side in the following strengths: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg.

    • Cardizem LA is supplied in 30- and 90-count bottles for all dosage strengths.

    Storage

    • Storage conditions: Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Avoid excessive humidity and temperatures above 30°C (86°F).

    Manufacturer

    Bausch Health Companies Inc.

    Mechanism of Action

    The therapeutic effects of diltiazem are believed to be related to its ability to inhibit the cellular influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle. The antihypertensive effect of diltiazem is produced primarily by relaxation of vascular smooth muscle and the resultant decrease in peripheral vascular resistance.

    Cardizem La Indications

    Indications

    Hypertension.

    Cardizem La Dosage and Administration

    Adult

    Swallow whole; take at the same time each day (AM or PM). Initially 180–240mg once daily; adjust at 2-week intervals up to max 540mg/day. Concomitant simvastatin: max 240mg/day.

    Children

    Not established.

    Cardizem La Contraindications

    Contraindications

    Sick sinus syndrome, 2nd- or 3rd-degree AV block unless paced. Hypotension. Acute MI and pulmonary congestion documented by X-ray on admission.

    Cardizem La Boxed Warnings

    Not Applicable

    Cardizem La Warnings/Precautions

    Warnings/Precautions

    CHF. Renal or hepatic impairment (monitor). Discontinue if persistent rash occurs. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

    Warnings/Precautions

    Bradycardia or AV Block

    • 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 additive effects on cardiac conduction.

    Heart Failure (HF)

    • Patients with preexisting impairment of ventricular function may develop worsening of CHF.

    • Use caution when using in combination with beta-blockers among patients with impaired ventricular function.

    Acute Hepatic Injury

    • Significant elevations in liver enzymes such as alkaline phosphatase, LDH, AST (SGOT), ALT (SGPT) and signs of acute hepatic injury have been reported with diltiazem therapy. 

    • Mild elevations of transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed in clinical studies.

    • These reactions have been transient and frequently resolved even with continued diltiazem treatment. Moreover, the reactions have typically occurred early after initiating treatment and were reversible with discontinuation of therapy.

    Severe Skin Reactions

    • Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and/or exfoliative dermatitis have been reported.

    Pregnancy Considerations

    • No well-controlled studies in pregnant women. Use diltiazem in pregnant women only if the potential benefit justifies the potential risk to the fetus.

    Nursing Mother Considerations

    • Diltiazem is excreted in human milk.

    • Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or diltiazem.

    Pediatric Considerations

    • Safety and efficacy in pediatric patients have not been established.

    Geriatric Considerations

    • Use caution in elderly patients and select dose starting at the low end of the range due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    Cardizem La Pharmacokinetics

    Absorption

    • Peak plasma levels of Cardizem LA 360 mg are reached between 11 and 18 hours.

    Distribution

    • 70–80% plasma protein bound.

    Metabolism

    Hepatic.

    Elimination

    Renal. Half-life: 6–9hrs.

    Cardizem La Interactions

    Interactions

    Concomitant ivabradine, rifampin, alcohol: avoid. Caution with digoxin, β-blockers, others that may affect cardiac conduction (may lead to AV block). Monitor heart rate with concomitant clonidine. Potentiates propranolol, benzodiazepines, buspirone, cyclosporine, carbamazepine, quinidine, lovastatin, simvastatin (limit to max 10mg/day); monitor. Caution with CYP3A4 substrates, inhibitors (eg, cimetidine), or inducers. Anesthetics may potentiate cardiac depression.

    Cardizem La Adverse Reactions

    Adverse Reactions

    Edema, headache, fatigue, dizziness, asthenia, 1st-degree AV block, bradycardia, rash (may be serious); rare: hypotension, liver abnormalities.

    Adverse Reactions

    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, fatigue, bradycardia, first-degree AV block and cough in patients treated for angina. 

    The following events were reported infrequently (<1%) in angina or hypertension trials:

    • Cardiovascular: Angina, bundle branch block, palpitations, syncope, tachycardia, ventricular extrasystoles. 

    • Nervous System: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tinnitus, tremor.

    • Gastrointestinal: Anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, thirst, vomiting, weight increase.

    • Dermatological: Petechiae, photosensitivity, pruritus, urticaria.  

    • Other: Amblyopia, CPK increase, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties.

    Cardizem La Clinical Trials

    Clinical Trials

    Hypertension

    • The efficacy of Cardizem LA at doses ranging from 120 to 540 mg once daily in the morning was evaluated in a randomized, double-blind, parallel, dose-response study which included 478 patients with essential hypertension. 

      • The mean reductions in diastolic blood pressure by ABPM (ambulatory blood pressure monitoring) at roughly 24 hours after the morning (4 AM to 8 AM) or evening (6 PM to 10 PM) administration (ie, the time corresponding to expected trough serum concentrations) for 120 mg, 240 mg, 360 mg, and 540 mg were –2.0, –4.4, and –8.1 mmHg, respectively, for evening doses, and for the morning dose of 360mg was –6.4 mmHg..

    • In a second randomized, double-blind, parallel-group, dose-response study, 258 patients received morning doses of either placebo or Cardizem LA 120 mg, 180 mg, 300 mg, or 540 mg.

      • Diastolic blood pressure measured by supine office cuff sphygmomanometer at trough (7 AM to 9 AM) decreased in an apparently linear manner over the dosage range studied. 

      • Group mean changes for placebo, 120 mg, 180 mg, 300 mg and 540 mg were –2.6, –1.9, –5.4, –6.1, and –8.6 mm Hg, respectively.

    Cardizem La Note

    Not Applicable

    Cardizem La Patient Counseling

    See Literature

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