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Medication Safety Issues
Sound-alike/look-alike issues:
Cardizem® may be confused with Cardene®, Cardene SR®, Cardizem CD®, Cardizem SR®, cardiem, cortisone
Cartia XT® may be confused with Procardia XL®
Diltiazem may be confused with Calan®, diazepam, Dilantin®
Tiazac® may be confused with Tigan®, Tiazac® XC [CAN], Ziac®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (I.V. formulation) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Significant differences exist between oral and I.V. dosing. Use caution when converting from one route of administration to another.
International issues:
Cardizem® may be confused with Cardem® which is a brand name for celiprolol in Spain
Cartia XT® may be confused with Cartia® which is a brand name for aspirin in multiple international markets
Dilacor®: Brand name for digoxin in Serbia, a brand name for verapamil in Brazil, and a brand name for barnidipine in Argentina
Tiazac® may be confused with Tazac® which is a brand name for nizatidine in Australia
Tiazac® may be confused with Tiazac® XC which is a brand name for diltiazem available in Canada (not available in U.S.)
Pronunciation
(dil TYE a zem)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes extended release tablet
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral: Essential hypertension; chronic stable angina or angina from coronary artery spasm
Injection: Atrial fibrillation or atrial flutter; paroxysmal supraventricular tachycardia (PSVT)
Use: Unlabeled/Investigational
Pediatric hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic and embryotoxic effects have been demonstrated in small animals. There are no adequate and well-controlled studies in pregnant women.
Lactation
Enters breast milk/not recommended (AAP considers “compatible”)
Breast-Feeding Considerations
Freely diffuses into breast milk; however, the AAP considers diltiazem to be compatible with breast-feeding. Available evidence suggests safe use during breast-feeding.
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:
• Beta-blockers: Concomitant use with beta-blockers can result in conduction disturbances, hypotension, and worsened LV function; I.V. administration concomitantly or within a few hours of I.V. beta-blockers is contraindicated.
• Digoxin: Concomitant use with digoxin can result in conduction disturbances.
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), 2D6 (minor), 3A4 (major); Inhibits CYP2C9 (weak), 2D6 (weak), 3A4 (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
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. Risk D: Consider therapy modification
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
BusPIRone: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of BusPIRone. Risk D: Consider therapy modification
Calcium Channel Blockers (Dihydropyridine): Calcium Channel Blockers (Nondihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Dihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Exceptions: Clevidipine. Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CarBAMazepine: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CarBAMazepine. CarBAMazepine may increase the metabolism of Calcium Channel Blockers (Nondihydropyridine). 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 decrease the metabolism of Cardiac Glycosides. Risk D: Consider therapy modification
Cimetidine: May decrease the metabolism of Calcium Channel Blockers. 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
Corticosteroids (Systemic): Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy
CycloSPORINE: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of CycloSPORINE. CycloSPORINE may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). 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. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Dronedarone. Dronedarone may increase the serum concentration of Calcium Channel Blockers (Nondihydropyridine). 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. Risk X: Avoid combination
Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Fosaprepitant: May increase the serum concentration of Diltiazem. The active metabolite aprepitant is likely responsible for this effect. Diltiazem may increase the serum concentration of Fosaprepitant. Specifically, diltiazem may increase the concentration of the active metabolite aprepitant. Risk C: Monitor therapy
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 (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
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
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: May increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of Lovastatin. Management: Avoid concurrent use of diltiazem with lovastatin when possible. If used together, consider using lower lovastatin doses (max of 20 mg/day). Risk D: Consider therapy modification
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Exceptions: Azithromycin; Dirithromycin [Off Market]; 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 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 Inducers: May decrease the serum concentration of P-Glycoprotein 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 Inhibitors: May increase the serum concentration of P-Glycoprotein 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 decrease the metabolism of 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
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. Risk D: Consider therapy modification
QuiNIDine: Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of QuiNIDine. Risk D: Consider therapy modification
Quinupristin: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Ranolazine: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Ranolazine. Risk X: Avoid combination
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. Risk D: Consider therapy modification
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
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: May increase the serum concentration of Diltiazem. Diltiazem may increase the serum concentration of Simvastatin. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, consider using lower simvastatin doses (max of 20 mg/day). Risk D: Consider therapy modification
Tacrolimus: Calcium Channel Blockers (Nondihydropyridine) may decrease the metabolism of Tacrolimus. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase risk of hypotension or vasodilation).
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. Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), kola, licorice, yohimbe (may worsen hypertension). Avoid black cohosh, California poppy, coleus, garlic, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse (may have increased antihypertensive effect).
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), 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, norepinephrine, oxacillin, penicillin G potassium, pentamidine, piperacillin, potassium chloride, potassium phosphates, ranitidine, sodium nitroprusside, theophylline, ticarcillin/clavulanate potassium, tobramycin, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium. Incompatible: Diazepam, furosemide, lansoprazole, micafungin, phenytoin, rifampin, thiopental. Variable (consult detailed reference): Acetazolamide, acyclovir, aminophylline, ampicillin, ampicillin/sulbactam, heparin, hydrocortisone sodium succinate, insulin (regular), methylprednisolone sodium succinate, nafcillin, procainamide, sodium bicarbonate.
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
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, 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, 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: Patients ?60 years may respond to a lower initial dose (ie, 120 mg once daily using extended release capsule)
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)
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)
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: 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
Do not take any new medication during therapy unless approved by prescriber. Oral: Take as directed; do not alter dosage or discontinue therapy without consulting prescriber. Do not crush or chew extended release form. Avoid (or limit) alcohol and caffeine. May cause dizziness or lightheadedness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea or vomiting (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, fruit, or fiber may help); or diarrhea. Report chest pain, palpitations, irregular heartbeat; unusual cough, respiratory difficulty; swelling of extremities; muscle tremors or weakness; confusion or acute lethargy; skin rash; or other adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
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).
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: 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.
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
Assess other pharmacological or herbal products patient may be taking for potential interactions (eg, increased risk of bradycardia, conduction delays, decreased cardiac output). I.V. requires use of infusion pump and continuous cardiac and hemodynamic monitoring. Assess therapeutic effectiveness according to purpose for use (hypertension, angina, atrial fib/flutter or PSVT) and adverse reactions when beginning therapy, when changing dose, and periodically during long-term therapy. Teach patient appropriate use (oral), interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Capsule, extended release, 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®: 120 mg, 180 mg, 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, as hydrochloride [twice-daily dosing]: 60 mg, 90 mg, 120 mg
Injection, solution, as hydrochloride: 5 mg/mL (5 mL, 10 mL, 25 mL)
Injection, powder for reconstitution, as hydrochloride: 100 mg
Tablet, as hydrochloride: 30 mg, 60 mg, 90 mg, 120 mg
Cardizem®: 30 mg, 60 mg, 90 mg, 120 mg
Tablet, extended release, as hydrochloride:
Cardizem® LA: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Tiazac® XC [CAN; not available in U.S.]: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg
Pricing: U.S. (www.drugstore.com)
Capsule, 12-hour (Diltiazem HCl CR)
60 mg (60): $35.99
90 mg (60): $45.99
120 mg (60): $71.51
Capsule, 24-hour (Cardizem CD)
120 mg (30): $101.09
180 mg (30): $118.41
240 mg (30): $163.17
300 mg (30): $199.96
360 mg (30): $223.83
Capsule, 24-hour (Cartia XT)
120 mg (30): $23.99
180 mg (30): $27.99
240 mg (30): $43.99
300 mg (30): $58.99
Capsule, 24-hour (Dilacor XR)
120 mg (30): $79.49
180 mg (30): $91.58
240 mg (30): $86.39
Capsule, 24-hour (Dilt-CD)
120 mg (90): $99.99
180 mg (90): $109.99
240 mg (30): $59.99
300 mg (30): $65.99
Capsule, 24-hour (Dilt-XR)
120 mg (30): $28.30
Capsule, 24-hour (Diltia XT)
180 mg (30): $32.99
240 mg (30): $34.99
Capsule, 24-hour (Diltiazem HCl Coated Beads)
120 mg (30): $29.99
180 mg (30): $34.99
300 mg (30): $58.99
Capsule, 24-hour (Diltiazem HCl CR)
120 mg (90): $50.79
180 mg (100): $66.43
240 mg (90): $65.99
Capsule, 24-hour (Diltiazem HCl ER Beads)
120 mg (30): $25.99
180 mg (30): $29.99
240 mg (30): $38.99
300 mg (30): $46.99
360 mg (30): $47.99
420 mg (90): $136.98
Capsule, 24-hour (Taztia XT)
120 mg (30): $33.99
180 mg (30): $39.99
240 mg (30): $49.99
300 mg (30): $64.99
360 mg (30): $65.99
Capsule, 24-hour (Tiazac)
120 mg (30): $47.83
180 mg (30): $53.50
240 mg (30): $74.20
300 mg (30): $93.68
360 mg (30): $94.89
420 mg (30): $100.00
Tablet, 24-hour (Cardizem LA)
120 mg (30): $65.93
180 mg (30): $82.99
240 mg (30): $99.65
300 mg (30): $133.20
360 mg (30): $133.78
420 mg (30): $148.94
Tablets (Cardizem)
30 mg (90): $97.18
60 mg (90): $76.00
90 mg (90): $105.99
Tablets (Diltiazem HCl)
30 mg (90): $12.99
60 mg (90): $22.50
90 mg (90): $22.00
120 mg (90): $29.99
Extemporaneously Prepared
A 12 mg/mL oral liquid preparation made from tablets (regular, not sustained release) and 3 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®) was stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature (25°C) or under refrigeration (5°C); grind sixteen 90 mg tablets in a mortar into a fine powder; add 10 mL of the vehicle and mix well to form a uniform paste; mix while adding the vehicle in geometric proportions to almost 120 mL; transfer to a calibrated bottle and qs ad with vehicle to 120 mL; label “shake well” and “protect from light."
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.
References
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Antman EM, Anbe SC, Alpert JS, et al, “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction),” Circulation, 2004, 110(5):588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.
Braunwald E, Antman EM, Beasley JW, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),” J Am Coll Cardiol, 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.
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Flynn JT and Pasko DA, “Calcium Channel Blockers: Pharmacology and Place in Therapy of Pediatric Hypertension,” Pediatr Nephrol, 2000, 15(3-4):302-16.
Gibbons RJ, Abrams J, Chatterjee K, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina),” J Am Coll Cardiol, 2003, 41(1):159-68.
Gibson RS, Boden WE, Theroux P, et al, “Diltiazem and Reinfarction With Non-Q-Wave Myocardial Infarction,” N Engl J Med, 1986, 315(7):423-9.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
Karth GD, Geppert A, Neunteufl T, et al, “Amiodarone vs. Diltiazem for Rate Control in Critically Ill Patients With Atrial Tachyarrhythmias,” Crit Care Med, 2001, 29(6):1149-53.
Maron BJ, McKenna WJ, Danielson GK, et al, “American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines,” J Am Coll Cardiol, 2003, 42(9):1687-713.
Phillips BG, Gandhi AJ, Sanoski CA, et al, “Comparison of Intravenous Diltiazem and Verapamil for the Acute Treatment of Atrial Fibrillation and Atrial Flutter,” Pharmacotherapy, 1997, 17(6):1238-45.
Roberts SA, Diaz C, Nolan PE, et al, “Effectiveness and Costs of Digoxin Treatment for Atrial Fibrillation and Flutter,” Am J Cardiol, 1993, 72(7):567-73.
Steele RM, Schuna AA, and Schreiber RT, “Calcium Antagonist-Induced Gingival Hyperplasia,” Ann Intern Med, 1994, 120(8):663-4.
“The Effect of Diltiazem on Mortality and Reinfarction After Myocardial Infarction. The Multicenter Diltiazem Postinfarction Trial Research Group,” N Engl J Med, 1988, 319(7):385-92.
White WB, Lacourciere Y, Gana T, et al, “Effects of Graded-Release Diltiazem Versus Ramipril, Dosed at Bedtime, on Early Morning Blood Pressure, Heart Rate, and the Rate-Pressure Product,” Am Heart J, 2004, 148(4):628-34.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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