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Diltiazem


Pronunciation

 (dil TYE a zem)


U.S. Brand Names

 Cardizem®; Cardizem® CD; Cardizem® LA; Cardizem® SR [DSC]; Cartia XT™; Dilacor® XR; Diltia XT®; Taztia XT™; Tiazac®


Synonyms

 Diltiazem Hydrochloride


Generic Available

 Yes


Canadian Brand Names

 Alti-Diltiazem CD; Apo-Diltiaz®; Apo-Diltiaz CD®; Apo-Diltiaz SR®; Cardizem®; Cardizem® CD; Cardizem® SR; Gen-Diltiazem; Gen-Diltiazem SR; Med-Diltiazem; Novo-Diltazem; Novo-Diltazem-CD; Novo-Diltazem SR; Nu-Diltiaz; Nu-Diltiaz-CD; ratio-Diltiazem CD; Rhoxal-diltiazem CD; Rhoxal-diltiazem SR; Syn-Diltiazem®; Tiazac®


Use

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

 Investigational: Therapy of Duchenne muscular dystrophy


Pregnancy Risk Factor

 C


Pregnancy Implications

 Teratogenic and embryotoxic effects have been demonstrated in small animals.


Lactation

 Enters breast milk/not recommended (AAP considers "compatible")


Contraindications

 Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome; second- or third-degree AV block (except in patients with a functioning artificial pacemaker); hypotension (systolic <90 mm Hg); acute MI and pulmonary congestion


Warnings/Precautions

 Concomitant use with beta-blockers or digoxin can result in conduction disturbances. Avoid concurrent I.V. use of diltiazem and a beta-blocker. Use caution in left ventricular dysfunction (can exacerbate condition). Symptomatic hypotension can occur. Use with caution in hepatic or renal dysfunction.


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%), sinus congestion (1% to 2%)

<2%: Albuminuria, alkaline phosphatase increased, allergic reaction, amblyopia, amnesia, angina, anorexia, arrhythmia, AV block (second or third degree), bruising, bundle branch block, CHF, CPK elevated, crystalluria, depression, dreams abnormal, dry mouth, dysgeusia, ECG abnormalities, epistaxis, gait abnormality, gynecomastia, hallucinations, hyperglycemia, hyperuricemia, impotence, insomnia, LDH increased, muscle cramps, nausea, neck rigidity, nocturia, pain, paresthesia, personality change, petechiae, photosensitivity, polyuria, pruritus, SGOT increased, SGPT increased, somnolence, syncope, tachycardia, thirst, tinnitus, tremor, ventricular extrasystoles, weight gain

Postmarketing and/or case reports: Alopecia, angioedema, asystole, bleeding time increased, erythema multiforme, exfoliative dermatitis, extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, leukopenia, purpura, retinopathy, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis


Overdosage/Toxicology

 Primary cardiac symptoms of calcium blocker overdose include hypotension and bradycardia. Noncardiac symptoms include confusion, stupor, nausea, vomiting, metabolic acidosis, and hyperglycemia.

Following initial gastric decontamination, if possible, repeated calcium administration may promptly reverse depressed cardiac contractility (but not sinus node depression or peripheral vasodilation). Glucagon, epinephrine, and amrinone may treat refractory hypotension. Glucagon and epinephrine also increase heart rate (outside the U.S., 4-aminopyridine may be available as an antidote). Dialysis and hemoperfusion are not effective in enhancing elimination although repeat-dose activated charcoal may serve as an adjunct with sustained-release preparations.


Drug Interactions

 Substrate of CYP2C8/9 (minor), 2D6 (minor), 3A4 (major); Inhibits CYP2C8/9 (weak), 2D6 (weak), 3A4 (moderate)

Alfentanil's plasma concentration is increased. Fentanyl and sufentanil may be affected similarly.

Amiodarone use may lead to bradycardia, other conduction delays, and decreased cardiac output; monitor closely if using together.

Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid this combination. Try an antifungal like terbinafine (if appropriate) or monitor closely for altered effect of the calcium channel blocker.

Benzodiazepines (midazolam, triazolam) plasma concentrations are increased by diltiazem; monitor for prolonged CNS depression.

Beta-blockers may have increased pharmacodynamic interactions with diltiazem (see Warnings/Precautions).

Buspirone: Diltiazem may increase serum levels of buspirone; monitor.

Calcium may reduce the calcium channel blocker's effects, particularly hypotension.

Carbamazepine's serum concentration is increased and toxicity may result; avoid this combination.

Cimetidine reduced diltiazem's metabolism; consider an alternative H2 antagonist.

Cyclosporine's serum concentrations are increased by diltiazem; avoid the combination. Use another calcium channel blocker or monitor cyclosporine trough levels and renal function closely.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of diltiazem. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of diltiazem. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

CYP3A4 substrates: Diltiazem may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, cyclosporine, mirtazapine, nateglinide, nefazodone, sildenafil (and other PDE-5 inhibitors), tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam), cisapride, ergot alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and simvastatin), and pimozide are generally contraindicated with strong CYP3A4 inhibitors.

Digoxin's serum concentration can be increased in some patients; monitor for increased effects of digoxin.

HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin): Serum concentration will likely be increased; consider pravastatin/fluvastatin or a second generation dihydropyridine calcium channel blocker as an alternative.

Lithium neurotoxicity may result when diltiazem is added; monitor lithium levels.

Moricizine's serum concentration is increased; monitor clinical response closely.

Nafcillin decreases plasma concentration of diltiazem; avoid this combination.

Nitroprusside's dose required reduction in patients started on diltiazem; monitor blood pressure.

Protease inhibitor like amprenavir and ritonavir may increase diltiazem's serum concentration.

Quinidine: Diltiazem may increase serum levels of quinidine. Dosage adjustment may be required.

Rifampin increases the metabolism of calcium channel blockers; adjust the dose of the calcium channel blocker to maintain efficacy or consider an alternative to rifampin.

Sildenafil, tadalafil, vardenafil: Blood pressure-lowering effects may be additive; use caution.

Tacrolimus's serum concentrations are increased by diltiazem; avoid the combination. Use another calcium channel blocker or monitor tacrolimus trough levels and renal function closely.


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 dong quai if using for hypertension (has estrogenic activity). Avoid ephedra (may worsen arrhythmia or hypertension). Avoid yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).


Stability

Capsule, tablet: Store at controlled room temperature.

Solution for injection: Store in refrigerator at 2°C to 8°C (36°F to 46°F). May be stored at room temperature for up to one month; do not freeze. Following dilution with D51/2NS, D5W, or NS, solution is stable for 24 hours at room temperature or under refrigeration.


Compatibility

 Stable in D5 1 /2NS, D5W, NS

Y-site administration: Compatible: Albumin, amikacin, amphotericin B, aztreonam, bretylium, bumetanide, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, clindamycin, digoxin, dobutamine, dopamine, doxycycline, epinephrine, erythromycin lactobionate, esmolol, fentanyl, fluconazole, gentamicin, hetastarch, hydromorphone, imipenem/cilastatin, labetalol, lidocaine, lorazepam, meperidine, metoclopramide, metronidazole, midazolam, milrinone, morphine, multivitamins, nicardipine, nitroglycerin, norepinephrine, oxacillin, penicillin G potassium, pentamidine, piperacillin, potassium chloride, potassium phosphates, ranitidine, sodium nitroprusside, theophylline, ticarcillin, ticarcillin/clavulanate potassium, tobramycin, trimethoprim/sulfamethoxazole, vancomycin, vecuronium. Incompatible: Diazepam, furosemide, phenytoin, rifampin, thiopental. Variable (consult detailed reference): Acetazolamide, acyclovir, aminophylline, ampicillin, ampicillin/sulbactam, cefamandole, cefoperazone, heparin, hydrocortisone sodium succinate, insulin (regular), methylprednisolone sodium succinate, nafcillin, procainamide, sodium bicarbonate


Mechanism of Action

 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: 70% to 80%

Distribution: Vd: 3-13 L/kg; enters breast milk

Protein binding: 77% to 85%

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 50% as potent as the parent compound.

Bioavailability: Oral: ~40% to 60%

Half-life elimination: Immediate release tablet: 3-4.5 hours, may be prolonged with renal impairment

Time to peak, serum: Immediate release tablet: 2-3 hours

Excretion: Urine and feces (primarily as metabolites)


Dosage

 Adults:

Oral:

Angina:

Capsule, extended release (Cardizem® CD, Cartia XT™, Dilacor XR®, Diltia XT™, Tiazac®): Initial: 120-180 mg once daily (maximum dose: 480 mg/day)

Tablet, extended release (Cardizem® LA): 180 mg once daily; may increase at 7- to 14-day intervals (maximum recommended dose: 360 mg/day)

Tablet, immediate release (Cardizem®): Usual starting dose: 30 mg 4 times/day; usual range: 180-360 mg/day

Hypertension:

Capsule, extended release (Cardizem® CD, Cartia XT™, Dilacor XR®, Diltia XT™, Tiazac®): Initial: 180-240 mg once daily; dose adjustment may be made after 14 days; usual dose range (JNC 7): 180-420 mg/day; Tiazac®: usual dose range: 120-540 mg/day

Capsule, sustained release (Cardizem® SR): Initial: 60-120 mg twice daily; dose adjustment may be made after 14 days; usual range: 240-360 mg/day

Tablet, extended release (Cardizem® LA): 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 (requires an infusion pump; 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: Start oral approximately 3 hours after bolus dose.

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 comments in renal/hepatic impairment: Use with caution as extensively metabolized by the liver and excreted in the kidneys and bile.

Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.


Administration

Oral: Do not crush long acting dosage forms.

Tiazac®: Capsules may be opened and sprinkled on a spoonful of applesauce. Applesauce should be swallowed without chewing, followed by drinking a glass of water.

I.V.: Bolus doses given over 2 minutes with continuous ECG and blood pressure monitoring. Continuous infusion should be via infusion pump.


Monitoring Parameters

 Liver function tests, blood pressure, ECG


Patient Education

 Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. 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 (buttermilk, boiled milk, or yogurt may help). 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.


Anesthesia and Critical Care Concerns/Other Considerations

 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. Intravenous diltiazem may be administered safely for up to 24 hours in patients with left ventricular dysfunction.


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


Dosage Forms

 [DSC] = Discontinued product

Capsule, extended release, as hydrochloride [once-daily dosing]: 120 mg, 180 mg, 240 mg, 300 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, Diltia XT®: 120 mg, 180 mg, 240 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, sustained release, as hydrochloride [twice-daily dosing] (Cardizem® SR [DSC]): 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 (Cardizem®): 25 mg

Tablet, as hydrochloride (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


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 Sys Pharm , 1996, 53(18):2179-84.


References

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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.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Ellenbogen KA, Dias VC, and Cardello FP, "Safety and Efficacy of Intravenous Diltiazem in Atrial Fibrillation or Atrial Flutter," Am J Cardiol , 1995, 75(1):45-9.

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.

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.

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.


International Brand Names

 Acalix® (AR); Acasmul® (CL); Adil® (BD); Adizem CD® (IL); Adizem® (LU); Adizem SR® (GB); Adizem XL® (GB, IE); Aldizem® (HR, PL, RO, SI, YU); Altiazem® (HK, IT, RO, RU, TH); Alti-Diltiazem CD (CA); Angidil® (IT); Angiodrox® (ES); Angiolong® (BR); Angiotrofin AP® (CR, DO, GT, HN, PA, SV); Angiotrofin® (CO, CR, DO, GT, HN, MX, PA, SV); Angiotrofin Retard® (CR, DO, GT, HN, PA, SV); Angiozem® (GB); Angitil SR® (GB); Angitil XL® (GB); Angizem® (IT, RU, TH); Apo-Diltiaz® (CA, PL); Apo-Diltiaz CD® (CA); Apo-Diltiazem® (NZ); Apo-Diltiaz SR® (CA); Asdilt® (RO); Auscard® (AU); Balcor® (BR, PT); Beatizem® (SG); Bi-Tildiem® (FR); Blocalcin® (CZ, HU, RU); Calcicard CR® (GB); Cardiacton® (AT); Cardiazem® (DK); Cardil® (BD, DK, EG, JO, KW, LB, RO, RU, SG, TH); Cardiser® (ES); Carditen® (ID); Cardium® (SG); Cardizem® (AU, BR, CA, DK, FI, NO, NZ, SE); Cardizem® CD (CA); Cardizem Retard® (SE); Cardizem® SR (CA); Cardizem Uno® (NO); Cardizem® Unotard (SE); Cardyne® (ID); Carreldon® (ES); Cascor XL® (TH); Chem mart Diltiazem® (AU); Clobendian® (ES); Cloridrato de Diltiazem® (BR); Coramil® (SE); Coras® (AU); Corazem® (AT, CO, EC); Corazet® (DE); Cordis® (CL); Coridil® (CH); Corolater® (ES); Cortiazem® (RU, YU); Corzem® (RO); Cronodine® (ES); DBL Diltiazem® (AU); Delay-Tiazem® (RO); Denazox® (CY, TH); Diacordin® (CZ, PL, RO, RU); Diacord® (RO); Diacor LP® (FR); Diazem® (RU, SG); Dilaclan® (ES); Dilacor XR® (NZ); Diladel® (IT); Dilahim Ahimsa® (AR); Dilatam® (IL, ZA); Dilauran® (AR); Dilazem® (BD); Dilcardia SR® (GB); Dilcard® (NZ); Dilcontin® (BD); Dilcontin Continus® (BD, IN); Dilcor® (DK); Dilem® (IT, TH); Dilfar® (PT); Diliter® (IT); Diliticard® (TR); Dilizem® (TH); Dilmen® (ID); Dilmin® (FI); Diloc® (NL); Dilpral® (FI); Dilrene® (HU); Dilsal® (DE); Dil-Sanorania® (DE); Dilso® (ID); Dilta 1A Pharma® (DE); Dilta AbZ® (DE); Diltabeta® (DE); Diltahexal® (AT, AU, DE); Dilta-Hexal® (LU); Diltam® (IE); Diltan® (HU, ID); Diltapham® (DE); Diltaretard® (DE); Diltec® (TH); Diltelan® (CH); Diltenk® (AR); Diltiacor® (BR); Diltiagamma® (DE); Diltiastad® (AT); Diltiasyn® (CO); Diltiax® (DO); Diltiazem AL® (DE); Diltiazem Alter® (ES); Diltiazem Basics® (DE); Diltiazem Bayvit® (ES); Diltiazem-BC® (AU); Diltiazem-B® (HU); Diltiazem® (CH, GB, HR, NO, PL, RO, RU); Diltiazem Cinfa® (ES); Diltiazem-Cophar® (CH); Diltiazem DOC® (IT); Diltiazem Dorom® (IT); Diltiazem Edigen® (ES); Diltiazem EG® (IT); Diltiazem Esteve® (ES); Diltiazem-Ethypharm® (LU); Diltiazem Eu Rho® (DE); Diltiazem Fada® (AR); Diltiazem Farmabion® (ES); Diltiazem Geminis® (ES); Diltiazem Genericon® (AT); Diltiazem Genfar® (EC); Diltiazem GNR® (IT); Diltiazem-GRY® (DE); Diltiazem Hennig® (DE); Diltiazem Heumann® (DE); Diltiazem Hydrochloride® (RO); Diltiazem-Isis® (DE); Diltiazem Lannacher® (RU); Diltiazem Lindo® (DE); Diltiazem-Mepha® (CH); Diltiazem Merck® (IT, PT); Diltiazem Mundogen® (ES); Diltiazem Northia® (AR); Diltiazem Pliva® (SI); Diltiazem Qualix® (ES); Diltiazem Ratiopharm® (AT); Diltiazem-ratiopharm® (BE, DE, IT, RU); Diltiazem R® (BG); Diltiazem RK® (IT); Diltiazem Sandoz® (DE); Diltiazem Stada® (DE); Diltiazem Teva® (IT); Diltiazem Verla® (DE); Diltiazem-Xl® (LU); Dilticard® (TR); Diltiem® (PT); Diltikard® (TR); Diltiphar® (BE); Diltiuc® (DE); dilti von ct® (DE); Diltiwas® (ES); Diltizem® (BR, RO, TR); Diltizem/Diltizem SR® (BD, TR); Dilzacard® (LB, RO); Dilzanton® (DE); Dilzem® (AT, AU, CH, CZ, DE, FI, HK, HU, IE, NZ, PL, RO, RU, TH); Dilzem Parenteral® (CZ, RO); Dilzem SR® (GB); Dilzem XL® (GB, IE); Dilzene® (IT); Dilzen-G® (AR); Dilzicardin® (DE); Dinisor® (ES); Ditizem® (TH); Doclis® (ES); Entrydil® (IE); Escozem® (CH); Etizem® (PT); Etyzem® (IT); Evascon® (BD); Farmabes® (ID); Gen-Diltiazem (CA); Gen-Diltiazem SR (CA); GenRX Diltiazem® (AU); Grifodilzem® (CL); Hart® (AR); Healthsense Diltiazem® (AU); Herbesser® (HK, ID, JP, PT, SG, TH); Incoril® (AR, CL, DO, HN, SV); Iski® (IN); Kaizem CD® (IN); Kaltiazem® (AR); Kardil® (TR); Lacerol® (DO, ES, GT, HN, SV); Levodex® (IL); Longazem® (IT); Masdil® (ES); Med-Diltiazem (CA); Medozem® (TH); Mono-Tildiem® (FR, LU); Mono-Tildiem SR® (SG); MTW-Diltiazem® (DE); Myonil® (DK); Neocard® (BD); Novo-Diltazem (CA); Novo-Diltazem-CD (CA); Novo-Diltazem SR (CA); Nu-Diltiaz (CA); Nu-Diltiaz-CD (CA); Optil® (GB); Oxycardil® (PL); Presokin A.P.® (AR); Progor® (BE); ratio-Diltiazem CD (CA); Rhoxal-diltiazem CD (CA); Rhoxal-diltiazem SR (CA); Rozen® (DO); Slozem® (GB); Surazem® (LU, NL); Syn-Diltiazem® (CA); Terry White Chemists Diltiazem® (AU); Tiadil® (NL); Tiakem® (RU); Tiazac® (CA); Tilazem® (AR, CL, CO, MX, ZA); Tildiem® (BE, CH, CL, FR, GB, HK, IE, IT, LU, NL); Tilker® (DK, ES, NO); Tilzem® (YU); Trumsal® (ES); Ubicor® (CH); Uni Masdil® (ES); Vasocardol CD (AU); Viazem® (DK, SE); Viazem XL® (GB); Zemtard® (GB); Zildem® (ZA); Zilden® (PL, RU)


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