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Pronunciation
(dil TYE a zem)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral: Essential hypertension; chronic stable angina or angina from coronary artery spasm
Injection: Control of rapid ventricular rate in patients with atrial fibrillation or atrial flutter; conversion of paroxysmal supraventricular tachycardia (PSVT)
Use: Unlabeled
ACLS guidelines: Injection: Stable narrow-complex tachycardia uncontrolled or unconverted by adenosine or vagal maneuvers or if SVT is recurrent
Pediatric hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic and embryotoxic effects have been demonstrated in animal reproduction studies.
Lactation
Enters breast milk/not recommended (AAP considers “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Diltiazem is excreted into breastmilk in concentrations similar to those in the maternal plasma.
Contraindications
Oral: Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except in patients with a functioning artificial pacemaker); second- or third-degree AV block (except in patients with a functioning artificial pacemaker); severe hypotension (systolic <90 mm Hg); acute MI and pulmonary congestion
Intravenous (I.V.): Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except in patients with a functioning artificial pacemaker); second- or third-degree AV block (except in patients with a functioning artificial pacemaker); severe hypotension (systolic <90 mm Hg); cardiogenic shock; administration concomitantly or within a few hours of the administration of I.V. beta-blockers; atrial fibrillation or flutter associated with accessory bypass tract (eg, Wolff-Parkinson-White syndrome); ventricular tachycardia (with wide-complex tachycardia, must determine whether origin is supraventricular or ventricular)
Canadian labeling: Additional contraindications (not in U.S. labeling): I.V. and Oral: Pregnancy; use in women of childbearing potential
Warnings/Precautions
Concerns related to adverse effects:
• Conduction abnormalities: May cause first-, second-, and third-degree AV block or sinus bradycardia; risk increases with agents known to slow cardiac conduction.
• Dermatologic reactions: Transient dermatologic reactions have been observed with use; if reaction persists, discontinue. May (rarely) progress to erythema multiforme or exfoliative dermatitis.
• Hepatic effects: Rarely, significant elevations in hepatic transaminases have been observed with use.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition.
• Peripheral edema: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose.
• Hypertrophic obstructive cardiomyopathy (HOCM): Use with caution in patients with HOCM; routineuse is currently not recommended due to insufficient evidence (Maron, 2003).
• Left ventricular dysfunction: Use with caution in left ventricular dysfunction; due to negative inotropic effects, may exacerbate condition. Avoid use of diltiazem in patients with heart failure and reduced ejection fraction (Hunt, 2009).
• Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy:
• Agents with SA/AV nodal-blocking properties: Use caution when using diltiazem together with a beta-blocker; may result in conduction disturbances, hypotension, and worsened LV function. Simultaneous administration of I.V. diltiazem and an I.V. beta-blocker or administration within a few hours of each other may result in asystole and is contraindicated. Use with other agents known to either reduce SA node function and/or AV nodal conduction (eg, digoxin) or reduce sympathetic outflow (eg, clonidine) may increase the risk of serious bradycardia.
Adverse Reactions
Note: Frequencies represent ranges for various dosage forms. Patients with impaired ventricular function and/or conduction abnormalities may have higher incidence of adverse reactions.
>10%:
Cardiovascular: Edema (2% to 15%)
Central nervous system: Headache (5% to 12%)
2% to 10%:
Cardiovascular: AV block (first degree 2% to 8%), edema (lower limb, 2% to 8%), pain (6%), bradycardia (2% to 6%), hypotension (<2% to 4%), vasodilation (2% to 3%), extrasystoles (2%), flushing (1% to 2%), palpitation (1% to 2%)
Central nervous system: Dizziness (3% to 10%), nervousness (2%)
Dermatologic: Rash (1% to 4%)
Endocrine & metabolic: Gout (1% to 2%)
Gastrointestinal: Dyspepsia (1% to 6%), constipation (<2% to 4%), vomiting (2%), diarrhea (1% to 2%)
Local: Injection site reactions: Burning, itching (4%)
Neuromuscular & skeletal: Weakness (1% to 4%), myalgia (2%)
Respiratory: Rhinitis (<2% to 10%), pharyngitis (2% to 6%), dyspnea (1% to 6%), bronchitis (1% to 4%), cough (≤3), sinus congestion (1% to 2%)
<2%: Albuminuria, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, amblyopia, amnesia, angina, anorexia, arrhythmia, AV block (second or third degree), bilirubin increased, bruising, bundle branch block, CHF, CPK increased, crystalluria, depression, dreams abnormal, ECG abnormalities, epistaxis, gait abnormality, gynecomastia, hallucination, hyperglycemia, hyperuricemia, impotence, insomnia, LDH increased, muscle cramps, nausea, neck rigidity, nocturia, pain, paresthesia, personality change, petechiae, photosensitivity, polyuria, pruritus, somnolence, syncope, tachycardia, taste disturbance, thirst, tinnitus, tremor, urticaria, ventricular extrasystoles, weight gain, xerostomia
Postmarketing and/or case reports: Alopecia, angioedema, asystole, bleeding time increased, erythema multiforme, exfoliative dermatitis, extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, leukocytoclastic vasculitis, leukopenia, myopathy, purpura, retinopathy, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis
Metabolism/Transport Effects
Substrate of CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (moderate)
Drug Interactions
Alfentanil: Diltiazem may increase the serum concentration of Alfentanil. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Amiodarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk D: Consider therapy modification
Anilidopiperidine Opioids: May enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Anilidopiperidine Opioids may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Aprepitant: May increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of Aprepitant. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a moderate CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. Risk C: Monitor therapy
Atorvastatin: May increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of Atorvastatin. Management: Consider using lower atorvastatin doses when used together with diltiazem. Risk D: Consider therapy modification
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Risk C: Monitor therapy
Benzodiazepines (metabolized by oxidation): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk D: Consider therapy modification
Beta-Blockers: Calcium Channel Blockers (Nondihydropyridine) may enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
BusPIRone: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of CarBAMazepine. Management: Consider empiric reductions in carbamazepine dose with initiation of nondihydropyridine calcium channel blockers. Monitor for increased toxic effects of carbamazepine and reduced therapeutic effects of the calcium channel blocker. Risk D: Consider therapy modification
Cardiac Glycosides: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification
Colestipol: May decrease the absorption of Diltiazem. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
Corticosteroids (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
CycloSPORINE: May decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE (Systemic). Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dronedarone: Calcium Channel Blockers (Nondihydropyridine) may enhance the AV-blocking effect of Dronedarone. Other electrophysiologic effects of Dronedarone may also be increased. Dronedarone may increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Dronedarone. Management: Use lower starting doses of the nondihydropyridine calcium channel blockers (i.e., verapamil, diltiazem), and only consider increasing calcium channel blocker dose after obtaining ECG-based evidence that the combination is being well-tolerated. Risk D: Consider therapy modification
Eletriptan: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Eletriptan. Risk C: Monitor therapy
Eplerenone: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Eplerenone. Risk C: Monitor therapy
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
Fingolimod: Diltiazem may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy
Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Fosaprepitant: Diltiazem may increase the serum concentration of Fosaprepitant. Specifically, diltiazem may increase the concentration of the active metabolite aprepitant. Fosaprepitant may increase the serum concentration of Diltiazem. The active metabolite aprepitant is likely responsible for this effect. Risk C: Monitor therapy
Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Grapefruit Juice: May increase the serum concentration of Diltiazem. Risk C: Monitor therapy
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Lithium: Calcium Channel Blockers (Nondihydropyridine) may enhance the neurotoxic effect of Lithium. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Lithium. Decreased or unaltered lithium concentrations have also been reported with this combination. Risk C: Monitor therapy
Lovastatin: Diltiazem may increase the serum concentration of Lovastatin. Lovastatin may increase the serum concentration of Diltiazem. Management: Initiate lovastatin at a maximum adult dose of 10 mg/day, and do not exceed 20 mg/day, in patients receiving diltiazem. Monitor closely for signs of HMG-CoA reductase inhibitor toxicity (e.g., myositis, rhabdomyolysis). Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Risk D: Consider therapy modification
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Monitor for increased therapeutic effects of calcium channel blockers if an interacting macrolide antibiotic is initiated, or decreased effects if a macrolide is discontinued. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Midodrine: Calcium Channel Blockers (Nondihydropyridine) may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If this combination is used, monitor for evidence of toxicity. The manufacturer of atazanavir recommends a 50% dose reduction for diltiazem be considered. Use of ritonavir with bepridil is contraindicated. Risk D: Consider therapy modification
QuiNIDine: Diltiazem may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
Ranolazine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Ranolazine. Management: Limit ranolazine dose to a maximum of 500 mg twice daily when used with diltiazem or verapamil. Risk D: Consider therapy modification
Red Yeast Rice: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin (and possibly other related compounds) may be increased. Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some U.S. and Canadian calcium channel blockers contraindicate use with rifampin however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Rivaroxaban: Diltiazem may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
Salicylates: Calcium Channel Blockers (Nondihydropyridine) may enhance the anticoagulant effect of Salicylates. Risk C: Monitor therapy
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy
Simvastatin: Diltiazem may increase the serum concentration of Simvastatin. Simvastatin may increase the serum concentration of Diltiazem. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, limit adult maximum simvastatin dose to 10 mg/day, and avoid Simcor (simvastatin/niacin) because fixed simvastatin doses in the product exceed this maximum. Risk D: Consider therapy modification
Tacrolimus: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus. Risk C: Monitor therapy
Tacrolimus (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Ethanol may increase risk of hypotension or vasodilation. Management: Avoid ethanol.
Food: Diltiazem serum levels may be elevated if taken with food. Serum concentrations were not altered by grapefruit juice in small clinical trials.
Herb/Nutraceutical: St John's wort may decrease diltiazem levels. Some herbal medications may worsen hypertension (eg, licorice); others may increase the antihypertensive effect of diltiazem (eg, shepherd's purse). Management: Avoid St John's wort, bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), kola, licorice, and yohimbe. Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, and shepherd's purse.
Storage
Capsule, tablet: Store at room temperature. Protect from light.
Solution for injection: Store in refrigerator at 2°C to 8°C (36°F to 46°F); do not freeze. May be stored at room temperature for up to 1 month. Following dilution to ≤1 mg/mL with D51/2NS, D5W, or NS, solution is stable for 24 hours at room temperature or under refrigeration.
Compatibility
Stable in D51/2NS, D5W, NS.
Y-site administration: Compatible: Albumin, alcohol (ethyl), amiodarone, amikacin, amphotericin B (conventional), argatroban, aztreonam, bivalirudin, bumetanide, caspofungin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, dexmedetomidine, digoxin, dobutamine, dopamine, doripenem, doxycycline, epinephrine, erythromycin lactobionate, esmolol, fenoldopam, fentanyl, fluconazole, gentamicin, hetastarch in lactated electrolyte injection (Hextend®), hydromorphone, imipenem/cilastatin, labetalol, lidocaine, lorazepam, meperidine, metoclopramide, metronidazole, midazolam, milrinone, morphine, multivitamins, nesiritide, nicardipine, nitroglycerin, nitroprusside, norepinephrine, oxacillin, pancuronium, penicillin G potassium, pentamidine, piperacillin, potassium chloride, potassium phosphates, ranitidine, sulfamethoxazole/trimethoprim, telavancin, terbutaline, theophylline, ticarcillin/clavulanate potassium, tobramycin, vancomycin, vasopressin, vecuronium. Incompatible: Diazepam, furosemide, micafungin, phenytoin, rifampin, thiopental. Variable (consult detailed reference): Acetazolamide, acyclovir, aminophylline, ampicillin, ampicillin/sulbactam, heparin, hydrocortisone sodium succinate, insulin (regular), methylprednisolone sodium succinate, metoprolol, nafcillin, procainamide, sodium bicarbonate, tenecteplase.
Compatibility in syringe: Incompatible: Ceftriaxone.
Mechanism of Action
Nondihydropyridine calcium channel blocker which inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina
Pharmacodynamics/Kinetics
Onset of action: Oral: Immediate release tablet: 30-60 minutes; I.V.: 3 minutes
Duration: I.V.: Bolus: 1-3 hours; Continuous infusion (after discontinuation): 0.5-10 hours
Absorption: Immediate release tablet: >90%; Extended release capsule: ~93%
Distribution: Vd: 3-13 L/kg
Protein binding: 70% to 80%
Metabolism: Hepatic (extensive first-pass effect); following single I.V. injection, plasma concentrations of N-monodesmethyldiltiazem and desacetyldiltiazem are typically undetectable; however, these metabolites accumulate to detectable concentrations following 24-hour constant rate infusion. N-monodesmethyldiltiazem appears to have 20% of the potency of diltiazem; desacetyldiltiazem is about 25% to 50% as potent as the parent compound.
Bioavailability: Oral: ~40% (undergoes extensive first-pass metabolism)
Half-life elimination: Immediate release tablet: 3-4.5 hours, may be prolonged with renal impairment; Extended release tablet: 6-9 hours; Extended release capsules: 5-10 hours; I.V.: single dose: ~3.4 hours; continuous infusion: 4-5 hours
Time to peak, serum: Immediate release tablet: 2-4 hours; Extended release tablet: 11-18 hours; Extended release capsule: 10-14 hours
Excretion: Urine (2% to 4% as unchanged drug; 6% to 7% as metabolites); feces
Dosage
Children (unlabeled use): Minimal information available; some centers use the following: Oral: Hypertension: Immediate release tablets: Initial: 1.5-2 mg/kg/day divided in 3 doses/day (maximum dose 6 mg/kg/day up to 360 mg/day) (Flynn, 2000)
Adults:
Oral:
Angina:
Capsule, extended release:
Dilacor XR®, Dilt-XR, Diltia XT®: Initial: 120 mg once daily; titrate over 7-14 days; usual dose range: 120-320 mg/day: maximum: 480 mg/day
Cardizem® CD, Cartia XT®, Dilt-CD: Initial: 120-180 mg once daily; titrate over 7-14 days; usual dose range: 120-320 mg/day; maximum: 480 mg/day
Tiazac®, Taztia XT®: Initial: 120-180 mg once daily; titrate over 7-14 days; usual dose range: 120-320 mg/day; maximum: 540 mg/day
Tablet, extended release (Cardizem® LA, Matzim™ LA, Tiazac® XC [CAN; not available in U.S.]): 180 mg once daily; may increase at 7- to 14-day intervals; usual dose range: 120-320 mg/day; maximum: 360 mg/day
Tablet, immediate release (Cardizem®): Usual starting dose: 30 mg 4 times/day; titrate dose gradually at 1- to 2-day intervals; usual dose range: 120-320 mg/day
Hypertension:
Capsule, extended release (once-daily dosing):
Cardizem® CD, Cartia XT®, Dilt-CD: Initial: 180-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (JNC 7): 180-420 mg/day; maximum: 480 mg/day
Dilacor® XR, Diltia XT®, Dilt-XR: Initial: 180-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (JNC 7): 180-420 mg/day; maximum: 540 mg/day
Tiazac®, Taztia XT®: Initial: 120-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (JNC 7): 180-420 mg/day; maximum: 540 mg/day
Capsule, extended release (twice-daily dosing): Initial: 60-120 mg twice daily; dose adjustment may be made after 14 days; usual range: 240-360 mg/day
Note: Diltiazem is available as a generic intended for either once- or twice-daily dosing, depending on the formulation; verify appropriate extended release capsule formulation is administered.
Tablet, extended release (Cardizem® LA, Matzim™ LA, Tiazac® XC [CAN; not available in U.S.]): Initial: 180-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (JNC 7): 120-540 mg/day
Note: Elderly: Consider lower initial doses (eg, 120 mg once daily using extended release capsule) and titrate to response (Aronow, 2011)
I.V.: Atrial fibrillation, atrial flutter, PSVT:
Initial bolus dose: 0.25 mg/kg actual body weight over 2 minutes (average adult dose: 20 mg); ACLS guideline recommends 15-20 mg
Repeat bolus dose (may be administered after 15 minutes if the response is inadequate): 0.35 mg/kg actual body weight over 2 minutes (average adult dose: 25 mg); ACLS guideline recommends 20-25 mg
Continuous infusion (infusions >24 hours or infusion rates >15 mg/hour are not recommended): Initial infusion rate of 10 mg/hour; rate may be increased in 5 mg/hour increments up to 15 mg/hour as needed; some patients may respond to an initial rate of 5 mg/hour.
If diltiazem injection is administered by continuous infusion for >24 hours, the possibility of decreased diltiazem clearance, prolonged elimination half-life, and increased diltiazem and/or diltiazem metabolite plasma concentrations should be considered.
Conversion from I.V. diltiazem to oral diltiazem:
Oral dose (mg/day) is approximately equal to [rate (mg/hour) x 3 + 3] x 10.
3 mg/hour = 120 mg/day
5 mg/hour = 180 mg/day
7 mg/hour = 240 mg/day
11 mg/hour = 360 mg/day
Dosing adjustment in renal impairment: Use with caution; no dosing adjustments recommended
Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
Dosing adjustment in hepatic impairment: Use with caution; no specific dosing recommendations available; extensively metabolized by the liver; half-life is increased in patients with cirrhosis
Administration: Oral
Immediate release tablet (Cardizem®): Administer before meals and at bedtime.
Long acting dosage forms: Do not open, chew, or crush; swallow whole.
Cardizem® CD, Cardizem® LA, Cartia XT®, Dilt-CD,Matzim™ LA: May be administered without regards to meals.
Dilacor XR®, Dilt-XR, Diltia XT®: Administer on an empty stomach.
Taztia XT™, Tiazac®: Capsules may be opened and sprinkled on a spoonful of applesauce. Applesauce should not be hot and should be swallowed without chewing, followed by drinking a glass of water.
Tiazac® XC [CAN; not available in U.S.]: Administer at bedtime
Administration: I.V.
Bolus doses given over 2 minutes with continuous ECG and blood pressure monitoring. Continuous infusion should be via infusion pump.
Administration: I.V. Detail
Response to bolus may require several minutes to reach maximum. Response may persist for several hours after infusion is discontinued.
pH: 3.7-4.1
Monitoring Parameters
Liver function tests, blood pressure, ECG, heart rate
Patient Education
Oral: Do not crush or chew extended release form. Avoid or limit alcohol and caffeine. May cause dizziness or lightheadedness, nausea, vomiting, or constipation. Report chest pain, palpitations, or irregular heartbeat; persistent diarrhea; unusual cough or respiratory difficulty; swelling of extremities; muscle tremors or weakness; confusion or acute lethargy; or skin rash.
Geriatric Considerations
Elderly may experience a greater hypotensive response; constipation may be encountered more often in elderly. Calcium channel blockers are no more effective in elderly than other therapies; however, they do not cause significant CNS effects which is an advantage over other antihypertensive agents (eg, beta-blockers, clonidine).
Cardiovascular Considerations
Diltiazem is an effective antihypertensive alone or in combination with other agents. Antihypertensive therapy should be individualized with consideration given to the patient's concomitant diseases and compelling indications for therapy.
In the treatment of acute myocardial infarction, diltiazem may be used to treat hypertension or ongoing ischemia if beta-blocker therapy is ineffective or contraindicated and in the absence of left ventricular dysfunction, pulmonary congestion, or AV block. In this setting, diltiazem may be beneficial. Diltiazem should be avoided in patients with left ventricular dysfunction or pulmonary congestion.
Diltiazem may be administered intravenously in the acute setting to attain ventricular rate control in patients with atrial fibrillation or flutter. Patients who respond, defined in general as at least a 20% decrease in ventricular response rate or attaining a rate <100 beats/minute, can be continued on oral therapy to maintain control. It is important to consider the potential drug interaction with digoxin, as these agents are both used in this setting.
In the treatment of unstable angina/non-ST-segment elevation MI, a nondihydropyridine calcium antagonist (diltiazem or verapamil) may be considered in patients with continuing or frequently recurring ischemia when beta-blockers are contraindicated (Class I). Oral long-acting calcium antagonists may also be considered in addition to beta-blockers and nitrates (Class IIa).
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Diltiazem has been reported to cause >10% incidence of gingival hyperplasia; usually disappears with discontinuation (consultation with physician is suggested).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness, insomnia, nervousness, or sedation
Mental Health: Effects on Psychiatric Treatment
May produce leukopenia; use caution with clozapine and carbamazepine; lithium levels may be increased or decreased; monitor serum lithium levels; benzodiazepines (midazolam, triazolam), buspirone, and carbamazepine levels may be increased; monitor for increased side effects
Nursing: Physical Assessment/Monitoring
Evaluate for use-related precautions prior to beginning therapy. Assess potential for interactions with other agents that may cause increased risk of bradycardia, conduction delays, or decreased cardiac output. I.V. requires use of infusion pump and continuous cardiac and hemodynamic monitoring. Assess therapeutic effectiveness according to use (hypertension, angina, atrial fib/flutter, or PSVT).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral, as hydrochloride [once-daily dosing]: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Cardizem® CD: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg
Cartia XT®: 120 mg, 180 mg, 240 mg, 300 mg
Dilacor XR®: 240 mg
Dilt-CD: 120 mg, 180 mg, 240 mg, 300 mg
Dilt-XR: 120 mg, 180 mg, 240 mg
Diltia XT®: 120 mg, 180 mg, 240 mg
Diltzac: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg
Taztia XT®: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg
Tiazac®: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Capsule, extended release, oral, as hydrochloride [twice-daily dosing]: 60 mg, 90 mg, 120 mg
Injection, powder for reconstitution, as hydrochloride: 100 mg
Injection, solution, as hydrochloride: 5 mg/mL (5 mL, 10 mL, 25 mL)
Tablet, oral, as hydrochloride: 30 mg, 60 mg, 90 mg, 120 mg
Cardizem®: 30 mg
Cardizem®: 60 mg, 90 mg, 120 mg [scored]
Tablet, extended release, oral, as hydrochloride [once-daily dosing]:
Cardizem® LA: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Matzim™ LA: 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 12-hour (Diltiazem HCl CR)
60 mg (60): $62.99
90 mg (60): $71.99
120 mg (60): $92.87
Capsule, 24-hour (Cardizem CD)
120 mg (30): $114.44
180 mg (30): $145.08
240 mg (30): $199.92
300 mg (30): $249.89
360 mg (30): $300.00
Capsule, 24-hour (Dilacor XR)
120 mg (30): $77.99
180 mg (30): $98.89
240 mg (30): $113.21
Capsule, 24-hour (Diltiazem HCl Coated Beads)
120 mg (30): $29.99
180 mg (30): $34.99
240 mg (30): $43.99
300 mg (30): $58.99
Capsule, 24-hour (Diltiazem HCl CR)
120 mg (90): $55.99
180 mg (100): $69.98
240 mg (90): $67.99
Capsule, 24-hour (Diltiazem HCl ER Beads)
120 mg (30): $29.99
180 mg (30): $35.99
240 mg (30): $45.99
300 mg (30): $56.99
360 mg (30): $49.99
420 mg (90): $159.98
Capsule, 24-hour (Taztia XT)
120 mg (30): $29.99
180 mg (30): $35.99
240 mg (30): $49.99
360 mg (30): $65.99
Capsule, 24-hour (Tiazac)
120 mg (30): $50.70
180 mg (30): $56.70
240 mg (30): $78.65
300 mg (30): $92.99
360 mg (30): $100.99
420 mg (30): $99.99
Tablet, 24-hour (Cardizem LA)
120 mg (30): $99.99
180 mg (30): $87.99
240 mg (30): $120.00
300 mg (30): $148.24
360 mg (30): $139.99
420 mg (30): $180.00
Tablet, 24-hour (Matzim LA)
180 mg (30): $88.99
240 mg (30): $97.99
300 mg (30): $128.00
420 mg (30): $145.99
Tablets (Cardizem)
30 mg (90): $119.06
Tablets (Diltiazem HCl)
30 mg (90): $12.99
60 mg (90): $22.50
90 mg (90): $22.99
120 mg (90): $29.99
Extemporaneously Prepared
A 12 mg/mL oral suspension may be made from tablets (regular, not extended release) and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet® and Ora-Plus®, or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®). Crush sixteen 90 mg tablets in a mortar and reduce to a fine powder. Add 10 mL of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well” and “protect from light". Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated.
Allen LV and Erickson MA, “Stability of Baclofen, Captopril, Diltiazem Hydrochloride, Dipyridamole, and Flecainide Acetate in Extemporaneously Compounded Oral Liquids,” Am J Health Syst Pharm, 1996, 53(18):2179-84.
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International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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