Diltiazem Hydrochloride
(British Approved Name Modified, US Adopted Name, rINNM)
Drug Nomenclature
INNs in main languages (French, Latin, Russian, and Spanish):
Pharmacopoeias. In China, Europe, Japan, and US.
European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Diltiazem Hydrochloride). A white or almost white, crystalline powder. Freely soluble in water, in dichloro-methane, and in methyl alcohol; slightly soluble in dehydrated alcohol. The pH of a 1% solution in water is 4.3 to 5.3. Store in airtight containers. Protect from light.
The United States Pharmacopeia 31, 2008, and Supplements 1 and 2 (Diltiazem Hydrochloride). A white, odourless, crystalline powder, or small crystals. Freely soluble in water, in chloroform, in formic acid, and in methyl alcohol; sparingly soluble in dehydrated alcohol; insoluble in ether. Store in airtight containers. Protect from light.
Adverse Effects
Treatment with diltiazem is generally well tolerated. Headache, ankle oedema, hypotension, dizziness, flushing, fatigue, and nausea and other gastrointestinal disturbances (including anorexia, vomiting, constipation or diarrhoea, taste disturbances, and weight gain) may occur. Gingival hyperplasia has been reported. Rashes, possibly due to hyper sensitivity, are normally mild and transient, but in a few cases erythema multi-forme or exfoliative dermatitis has developed; photo-sensitivity reactions may also occur. Transient elevations in liver enzyme values, and occasionally hepatitis, have been reported.
Diltiazem may depress cardiac conduction and has occasionally led to AV block, bradycardia, and rarely asystole or sinus arrest.
Overdosage with diltiazem may be associated with bradycardia, with or without AV conduction defects, and hypotension.
Diltiazem has been shown to cause teratogenicity in animal studies.
Effects on mortality. For discussion of the possibility that calcium-channel blockers might be associated with increased cardiovascular mortality, see under Adverse Effects of Nifedipine.
Angioedema. Periorbital angioedema, accompanied by pruritus or burning and erythema developed in 2 patients given diltiazem.
Effects on the blood. Thrombocytopenia has been reported in association with diltiazem.
Effects on carbohydrate metabolism. Although raised blood-glucose concentrations and insulin requirements have been reported in a patient with type 1 diabetes mellitus during diltiazem therapy, particularly at high doses, a study in 11 obese black women, who were nondiabetic but had a family history of type 2 diabetes, failed to find any effect of diltiazem 240 mg daily on plasma-glucose and C-peptide concentrations, nor any clinical signs of glucose intolerance.
Effects on the ears. There have been isolated reports of tinnitus associated with several calcium-channel blockers including nifedipine, nicardipine, nitrendipine, diltiazem, verapamil, and cinnarizine.
Effects on the gastrointestinal tract. Gastrointestinal disturbances including nausea, vomiting, and constipation, may occur with calcium-channel blockers. A case of intestinal pseudo-obstruction was reported in a 74-year-old neutropenic man receiving chemotherapy for leukaemia after diltiazem was added to treat new-onset atrial fibrillation. A diagnosis of neutropenic enterocolitis was ruled out and symptoms resolved when diltiazem was stopped; it was concluded that diltiazem was the probable cause. A similar case attributed to verapamil has been reported.
Effects on the heart. AV BLOCK. AV block appears to be uncommon in patients receiving diltiazem, but is potentially serious when it occurs. Prescription-event monitoring of a cohort of 10 119 patients for 1 year revealed 22 reports of AV block during diltiazem treatment. At least 8 patients had third-degree heart block, and 12 required a pacemaker; 3 died within 72 hours of the onset of heart block. A high proportion of these patients were also receiving beta blockers, which is in line with other reports. (See also Beta Blockers under Interactions, below.) There is some evidence that the incidence of this effect may depend on the serum concentration of diltiazem. In a study in patients receiving diltiazem after myocardial infarction, patients with serum-diltiazem concentrations greater than 150 nanograms/mL were more likely to experience AV block than patients with concentrations of diltiazem below this value.
MYOCARDIAL INFARCTION. Results from at least one large multicentre study (the Multicenter Diltiazem Postinfarction Trial) suggest that diltiazem, although apparently of benefit after myocardial infarction in patients with normal left ventricular function (as indicated by absence of pulmonary congestion), was associated with an increased risk of cardiac death or non-fatal re-infarction in patients with impaired left ventricular function. Long-term follow-up indicated that diltiazem also increased the risk of late-onset heart failure in postinfarction patients with left ventricular dysfunction.
WITHDRAWAL. Life-threatening coronary vasospasm, which was fatal in one patient, occurred in 4 patients after coronary revascularisation for unstable angina. Treatment with a calcium-channel blocker (diltiazem or nifedipine) had been discontinued between 8 and 18 hours before the procedure and this abrupt withdrawal was thought to be responsible for the rebound vasospasm. The coronary vasospasm was managed with glyceryl trinitrate and nifedipine.
Withdrawal of diltiazem over a 4-day period from a patient with stable angina pectoris was followed by recurrence of anginal attacks. Ambulatory ECG monitoring confirmed worsening myocardial ischaemia that responded to re-introduction of diltiazem. Two further patients had a similar withdrawal effect.
Effects on the kidneys. Diltiazem may be of benefit in various kidney disorders (see under Uses, below). However, there are a few reports of acute renal failure associated with diltiazem use. Acute interstitial nephritis has been proposed as a mechanism.
Effects on mental function. By September 1989, the WHO collaborative programme for international drug monitoring had gathered 8 cases of mental depression (severe in 2) associated with diltiazem therapy. Time of onset of symptoms varied from a few hours to a few months after starting treatment with diltiazem. There was some evidence that the problem might be dose-related as 5 of the 8 cases were receiving doses of 180 mg daily or more.
Psychoses have been reported rarely in association with diltiazem. A patient who developed hallucinations (both auditory and visual) and paranoid delusions after 2 days of diltiazem therapy was subsequently treated with nifedipine without abnormal effects. Another patient with bipolar affective disorder that had been well-controlled by lithium carbonate for some years developed acute psychosis with extrapyramidal symptoms of cogwheel rigidity and ataxia, which was thought to represent an interaction between diltiazem and lithium.
Effects on the mouth. A study involving 115 patients given nifedipine, diltiazem, or verapamil for at least 3 months indicated that gingival hyperplasia is an important side-effect that may occur with calcium-channel blockers.
Effects on the nervous system. Akathisia has been reported in a patient the day after starting treatment with diltiazem. Symptoms disappeared when diltiazem was withdrawn and recurred on rechallenge after the third dose. Similar symptoms in association with mania have also been reported in another patient given diltiazem.
PARKINSONISM. Parkinsonism developed in an elderly patient with heart disease and hypertension when diltiazem was added to existing drug therapy. Symptoms worsened over 3 months but improved significantly when diltiazem was slowly withdrawn. On rechallenge severe tremor, impaired gait, and cogwheel rigidity recurred, but resolved when the drug was stopped again except for slight residual cogwheel rigidity.
An acute parkinsonian syndrome also developed in a patient taking lithium and tiotixene when diltiazem was added, and was thought to represent an interaction between lithium and diltiazem. See also Effects on Mental Function, above.
Effects on the skin. A variety of skin disorders have been associated with diltiazem therapy, including acute pustular dermatitis, cutaneous vasculitis, erythema multiforme, pruritic macular rashes, severe toxic erythema, subacute lupus erythematosus-like eruptions, and photo sensitivity reactions. Analysis of cutaneous adverse reactions to diltiazem indicated that acne, rash, and urticaria were among the commonest. There have also been a few reports of exfoliative dermatitis, erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis.
For a report of periorbital skin rash associated with diltiazem, see Angioedema, above.
Cross-sensitivity, manifest as a pruritic maculopapular rash, has been reported between diltiazem and amlodipine.
Overdosage. See under Treatment of Adverse Effects, below.
Treatment of Adverse Effects
As for Nifedipine, but see also below.
Diltiazem and its metabolites are poorly dialysable.
Overdosage. The consequences and treatment of diltiazem overdosage are similar to nifedipine, although death and life-threatening complications might be more common with diltiazem. Up to 1994, 6 cases of fatal overdose with diltiazem had been reported in the literature. Measurement of diltiazem concentrations to assist in diagnosis and management of overdosage has been suggested, but others have disputed its value. The following are individual reports of overdosage with diltiazem:
• A patient who took about 10.8 g of diltiazem developed hypotension and complete heart block. Dopamine, isoprenaline, and calcium chloride were required to maintain the blood pressure. The ECG reverted to sinus rhythm after 31 hours. The plasma-diltiazem concentration was 1670 nanograms/mL 43 hours after ingestion and fell to 12.1 nanograms/mL over a further 55.5 hours with an elimination half-life of 7.9 hours.
• In a further case a patient took 5.88 g of diltiazem with alcohol, and developed severe junctional bradycardia, hypotension, and reduced cardiac function that did not respond to intravenous calcium gluconate. The maximum plasma-diltiazem concentration of 6090 nanograms/mL occurred 7 hours after presentation. About half of the dose was vomited after treatment with activated charcoal. The patient was treated with cardiac pacing and a dopamine infusion; he reverted to sinus rhythm within 24 hours, and a subsequent episode of atrial fibrillation was treated successfully with digoxin.
• Charcoal haemoperfusion had a limited effect in improving the clearance of diltiazem in a patient who had taken 14.94 g of diltiazem. The patient developed severe hypotension, complete heart block, and acute renal failure. Supportive care included cardiac pacing and numerous vasopressors including intravenous glucagon and infusions of dopamine, adrenaline, and noradrenaline.
Precautions
Diltiazem is contra-indicated in patients with the sick sinus syndrome, pre-existing second- or third-degree AV block, or marked bradycardia, and should be used with care in patients with lesser degrees of AV block or bradycardia. Diltiazem has been associated with the development of heart failure and great care is required in patients with impaired left ventricular function. Sudden withdrawal of diltiazem might be associated with an exacerbation of angina.
Treatment with diltiazem should begin with reduced doses in elderly patients and in patients with hepatic or renal impairment.
Abuse. Abuse of diltiazem by body builders and rugby players has been alleged. Such abuse is possibly because of evidence that diltiazem increases maximum oxygen consumption after training. A body builder who admitted to taking diltiazem in high doses suffered severe abdominal cramps.
Breast feeding. Diltiazem is distributed into breast milk; in a woman receiving oral diltiazem 60 mg four times daily, concentrations in breast milk were similar to those in serum. The manufacturers therefore recommend that diltiazem should generally be avoided during breast feeding. However, in another report, a mother breast fed twins for at least 6 months while receiving diltiazem and no adverse effects were reported in the infants. Since there have been no reports of adverse effects, the American Academy of Pediatrics considers that diltiazem is usually compatible with breast feeding.
Porphyria. Diltiazem is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals or in-vitro systems.
Renal impairment. A patient with end-stage renal failure requiring haemodialysis developed hypotension, bradycardia, metabolic acidosis, hyperkalaemia, and acute congestive heart failure about 60 hours after his last haemodialysis. The patient had been taking diltiazem 60 mg three times daily. The symptoms were attributed to diltiazem toxicity due to accumulation of diltiazem and its metabolites which are poorly dialysed and normally excreted partially in the urine.
Interactions
Increased depression of cardiac conduction with risk of bradycardia and AV block may occur when diltiazem is given with drugs such as amiodarone, beta blockers, digoxin, and mefloquine. Enhanced antihypertensive effect may occur if used with other antihypertensive drugs or drugs that cause hypotension such as aldesleukin and antipsychotics. Diltiazem is extensively metabolised in the liver by the cytochrome P450 isoenzyme CYP3 A4 and may also inhibit the metabolism of drugs sharing the same pathway. Interactions may also be expected with enzyme inducers, such as carbamazepine, phenobarbital, phenytoin, and rifampicin, and with enzyme inhibitors, such as cimetidine and HIV-protease inhibitors.
Antidepressants. For a report of diltiazem increasing the bio-availability of imipramine and nortriptyline, see Calcium-channel Blockers under the Interactions of Amitriptyline.
Antiepileptics. For reports of diltiazem use precipitating carbamazepine and phenytoin toxicity, respectively.
Anxiolytics. For the effect of diltiazem on plasma-buspirone concentrations.
Benzodiazepines. For the effects of diltiazem on plasma concentrations of midazolam or triazolam, see Calcium-channel Blockers under Interactions of Diazepam.
Beta blockers. Profound bradycardia has been reported in a number of patients when diltiazem was used with a beta blocker. Diltiazem decreases the clearance of a single dose of propranolol or metoprolol, though not atenolol, and elevated concentrations of beta blocker may be responsible for the bradycardic effects. This is unlikely to be the full story, however, since atenolol, which was unaffected in this study, has been implicated in producing bradycardia when diltiazem was added in a patient with myocardial ischaemia.
Calcium-channel blockers. For the effect of diltiazem and nifedipine on each other’s plasma concentrations.
Ciclosporin. For reports of a potentially beneficial interaction between diltiazem and ciclosporin, see Transplantation under Uses and Administration, below.
Corticosteroids. Diltiazem has been reported to reduce the clearance of methylprednisolone (see Calcium-channel Blockers).
Digoxin. For a discussion of interactions between digoxin and calcium-channel blockers including diltiazem.
General anaesthetics. Two patients on diltiazem therapy developed impaired myocardial conduction during anaesthesia with enflurane; one of the patients had severe sinus bradycardia that progressed to asystole. Additive cardiodepressant effects of diltiazem and enflurane were considered responsible.
Histamine H2-antagonists. Cimetidine caused increases in plasma-diltiazem concentrations and in plasma-deacetyldiltiazem concentrations in 6 subjects given a single oral dose of diltiazem 60 mg. Ranitidine produced a similar, though less marked effect.
Lithium. Neurotoxicity has been reported in patients receiving lithium and diltiazem, see Effects on Mental Function and Parkinsonism under Effects on the Nervous System, above.
Theophylline. For the effect of diltiazem on plasma-theophylline concentrations.
Pharmacokinetics
Diltiazem is almost completely absorbed from the gastrointestinal tract after oral doses, but undergoes extensive first-pass hepatic metabolism. Peak plasma concentrations occur about 3 to 4 hours after an oral dose. The bioavailability has been reported to be about 40%, although there is considerable interindividual variation in plasma concentrations. Diltiazem is about 80% bound to plasma proteins. It is distributed into breast milk. It is extensively metabolised in the liver, primarily by the cytochrome P450 isoenzyme CYP3A4; one of the metabolites, desacetyldiltiazem, has been reported to have 25 to 50% of the activity of the parent compound. The half-life of diltiazem is reported to be about 3 to 5 hours. About 2 to 4% of a dose is excreted in urine as unchanged diltiazem with the remainder excreted as metabolites in bile and urine. Diltiazem and its metabolites are poorly dialysable.
Bioavailability. Studies of the pharmacokinetics of diltiazem in healthy subjects after single and multiple doses, indicated that bioavailability was increased after multiple doses, probably because of decreased presystemic elimination.
Renal impairment. The pharmacokinetics of diltiazem and its major metabolite desacetyldiltiazem in patients with severe renal impairment were similar to those in patients with normal renal function. Nevertheless, reduced doses may be necessary in patients with renal impairment (see under Uses and Administration below). See also under Precautions, above.
Uses and Administration
Diltiazem is a benzothiazepine calcium-channel Mocker and class IV antiarrhythmic. It is a peripheral and coronary vasodilator with limited negative inotropic activity but its vasodilator properties are less marked than those of the dihydropyridine calcium-channel blocker nifedipine. Unlike nifedipine, diltiazem inhibits cardiac conduction, particularly at the sinoatrial and atrioventricular nodes. Diltiazem hydrochloride is given orally in the management of angina pectoris and hypertension and is available in a number of formulations for dosage once, twice, or three times daily. In some countries it is available for intravenous use in the treatment of various cardiac arrhythmias (atrial fibrillation or flutter and paroxysmal supraventricular tachycardia). It has also been used topically in the management of anal fissure (see below).
The variety of formulations means that dosage is dependent on the preparation used. Reduced doses may be required in the elderly or those with renal or hepatic impairment (see below).
In angina pectoris an initial dose is 60 mg orally three times daily (or 30 mg four times daily in the USA), increased if necessary to 360 mg daily; up to 480 mg daily has sometimes been given. Formulations suitable for once- or twice-daily use may be given in doses of 120 to 480 mg daily; up to 540 mg daily has been given.
In hypertension diltiazem hydrochloride may be given as modified-release capsules or tablets. Depending on the formulation, an initial dose is 60 to 120 mg twice daily, increased as required to a maximum of 360 mg daily. Formulations suitable for once-daily dosage may be given in similar daily doses, although up to 540 mg daily has been given. In cardiac arrhythmias an initial dose of 250 micrograms/kg by bolus intravenous injection over 2 minutes has been suggested; a further dose of 350 micrograms/kg may be given after 15 minutes if the response is inadequate. Subsequent doses should be individualised for each patient. For those with atrial fibrillation or flutter, a continued reduction in heart rate may be achieved with an intravenous infusion of diltiazem hydrochloride after the bolus injection. An initial infusion rate of 5 to 10 mg/hour, may be increased as necessary in increments of 5 mg/hour up to a rate of 15 mg/hour. The infusion may be continued for up to 24 hours.
Action. The haemodynamic and electrophysiological effects of diltiazem appear to resemble those of verapamil more than those of nifedipine. It inhibits sino-atrial and atrioventricular nodal function in doses used clinically. The effects on sino-atrial function are more pronounced than those observed after verapamil. Diltiazem causes a decrease in the rate-pressure product indicating that decreased oxygen demand is a likely mechanism of action in relieving angina pectoris. Like verapamil, but unlike nifedipine, diltiazem does not appear to cause significant increases in coronary blood flow. The negative inotropic effect of diltiazem is presumably counteracted by afterload reduction.
Administration in hepatic or renal impairment. The dose of diltiazem hydrochloride may need to be reduced in patients with hepatic or renal impairment, and in the elderly. In the UK an initial dose of 120 mg daily is usually suggested, as a single dose or in 2 divided doses by mouth depending on the formulation. The dose may be increased cautiously, but only if the heart rate remains above 50 beats/minute.
Anorectal disorders. Beneficial responses to diltiazem reported in 2 patients with proctalgiafugax may have been due to smooth muscle relaxation. The resting pressure of the internal anal sphincter was decreased by a mean of 20.6% in all but 1 of 13 subj ects given a single 60-mg oral dose of diltiazem. A small study has compared oral with topical diltiazem in the management of analfissure. Despite a higher response rate with the topical drug, no significant difference in benefit was seen between the 2 routes. A subsequent study suggested topical diltiazem (2%) might be of benefit in patients with anal fissure unresponsive to topical nitrates. Sustained benefit after a 6-week treatment course has also been reported in some patients.
Cardiomyopathies. Although calcium-channel blockers should be used with caution in patients with heart failure, symptomatic improvement has been reported in patients with dilated cardiomyopathy given diltiazem.
Connective tissue and muscular disorders. Subcutaneous deposition of calcium (calcinosis) can occur in a number of inflammatory conditions, particularly in juvenile dermatomyositis (see Polymyositis and Dermatomyositis). Treatment of calcinosis is difficult, but there have been a number of reports of the successful use of diltiazem in children and adults with dermatomyositis, as well as in adults with CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome, scleroderma, and lupus panniculitis. Another study, however, found only a limited response in patients with systemic sclerosis.
Kidney disorders. Calcium-channel blockers may be of benefit in various forms of kidney disorder (see Nifedipine). Diltiazem has been reported to reduce urinary protein excretion without exacerbating pre-existing renal dysfunction in diabetic patients. A small study in 15 hypertensive patients with type 2 diabetes mellitus, albuminuria, and renal impairment found that diltiazem only reduced urinary albumin excretion when patients received a restricted dietary sodium intake of 50 mmol daily.
Diltiazem may also reduce the nephrotoxicity associated with certain drugs. Reduced nephrotoxicity has been reported when diltiazem is given to healthy subjects receiving netilmicin, but diltiazem does not appear to modify the acute renal failure associated with tubular damage which may be caused by methotrex-ate. Diltiazem may reduce ciclosporin-induced nephrotoxicity (see Transplantation, below).
Migraine. For reference to the use of calcium-channel blockers, including diltiazem, in the management of migraine, see under Nifedipine.
Myocardial infarction. For reference to the use of diltiazem in the acute and long-term management of myocardial infarction, see under Uses of Verapamil.
Transplantation. Diltiazem increases blood-ciclosporin concentrations when given by mouth in doses of 60 to 180 mg daily to transplant patients receiving ciclosporin therapy. In consequence, ciclosporin doses can be reduced by about one-third, at a considerable saving in cost. However, the effect may not occur in all patients, and may vary with differing formulations, and it has been suggested that blood-ciclosporin concentrations should be closely monitored if diltiazem is used for this purpose. In addition to this effect, which is apparently due to non-competitive inhibition of ciclosporin metabolism by diltiazem, there is evidence of improved renal graft-function in patients given the combined therapy, suggesting that diltiazem may reduce ciclosporin-induced nephrotoxicity. However, a 4-year follow-up study in patients treated with ciclosporin and diltiazem found that diltiazem had no effect on the progression to chronic allograft nephropathy. Improved survival has been reported in a retrospective study of patients given diltiazem for its ciclosporin-sparing effect, but it was unclear if this was a direct effect of diltiazem or was related to other factors associated with its use.
Preparations
The United States Pharmacopeia 31, 2008, and Supplements 1 and 2: Diltiazem Hydrochloride Extended-re lease Capsules; Diltiazem Hydrochloride Oral Solution; Diltiazem Hydrochloride Oral Suspension; Diltiazem Hydrochloride Tablets.
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed
Argentina: Acalix; Dilahim; Diltenk; Diltiacor¤; Dilzen-G; Hart; Incoril; Kaltiazem; Ritmocit¤; Tilazem; Australia: Auscard¤; Cardcal¤; Cardizem; Coras; Diltahexal; Diltiamax¤; Dilzem; Vasocardol; Austria: Cardiacton¤; Corazem; Dilatame¤; Diltahexal; Diltiastad; Dilzatyrol¤; Dilzem; Gewazem¤; Belgium: Progor; Tildiem; Brazil: Angiolong; Balcor; Calzem; Cardizem; Diltiacor; Diltipress; Diltizem; Diltor; Incoril; Canada: Apo-Diltiaz; Cardizem; Novo-Diltazem; Nu-Diltiaz; Tiazac; Chile: Acasmul; Grifodilzem; Incoril; Tilazem; Tildiem; Czech Republic: Aldizem; Altiazem; Blocalcin; Diacordin; Dilzem; Etizem; Tiakem; Denmark: Angiact¤; Angicontin¤; Cardil; Cardizem; Dilcor; Myonil; Tilker; UnoCardil¤; Viazem¤; Finland: Cardizem; Dilmin; Dilpral; Dilzem; France: Bi-Tildiem; Deltazen; Diacor; Dilrene; Mono-Tildiem; Tildiem; Germany: Corazet¤; Dil-Sanorania; Dilsal; Dilta; Diltabeta; Diltahexal; Diltapham¤; Diltaretard; Dilti-Essex¤; Dilti; Diltiagamma; Diltiamerck¤; Diltiuc; Dilzanton; Dilzem; Dilzereal¤; Dilzicardin¤; Greece: Alfener; Cardil; Diltelan; Diltem¤; Dilzanol¤; Dipen; Elvesil; Ergoclavin; Mavitalon; Mycarzem¤; Rubiten; Saubasin; Ternel; Tildiem; Zem; Zilden; Hong Kong: Altiazem; Apo-Diltiaz¤; Cardium; Dilem¤; Diltan¤; Dilzem¤; Herbesser; Metazem¤; Retalzem¤; Tildiem¤; Wontizem; Hungary: Blocalcin; Dilrene; Diltan; Dilzem; India: Dilcardia¤; Dilcontin; Dilgard; Dilzem; DTM; Iski; Kaizem; Ireland: Adizem; Diltam; Dilzem; Entrydil; Metazem¤; Tildiem; Israel: Adizem; Dilatam; Levodex; Italy: Altiazem; Angidil¤; Angipress¤; Angizem; Carzem¤; Citizem¤; Diacardin; Diladel; Dilem; Diliter; Dilzene; Etyzem; Longazem; Tiakem¤; Tiazen¤; Tildiem; Zilden¤; Japan: Herbesser; Malaysia: Cardil; Cascor; Dilcard; Dilem; Herbesser; Mono-Tildiem; Mexico: Angiotrofin; Presoken; Presoquim; Sertidel; Tilazem; Waysen¤; Netherlands: Diloc; Surazem; Tiadil; Tildiem; Norway: Cardizem; Diltikard¤; Kardil¤; Tilker¤; New Zealand: Cardizem; Dilcard; Diltahexal; Dilzem; Portugal: Alandiem; Balcor; Cal-Antagon; Dilfar; Dilongo; Diltiangina; Diltiem; Duplide¤; Etizem; Herbesser; Pentilzeno¤; Tiadil; Russia: Altiazem (Алтиазем); Blocalcin (Блокальцин); Cardil (Кардил); Diazem (Диазем); Dilcardia (Дилкардия); South Africa: Anzem¤; Diatil¤; Dilatam; Tilazem; Zildem; Singapore: Altiazem¤; Angizem¤; Beatizem; Cardil; Cardium; Dilatam¤; Dilizem¤; Herbesser; Metazem¤; Mono-Tildiem; Tildiem¤; Spain: Angiodrox; Cardiser; Carreldon; Clobendian; Convectal¤; Corolater; Cronodine; Dilaclan; Diltiwas; Dinisor; Doclis; Lacerol; Masdil; Mdiltiwas¤; Tilker; Trumsal; Uni Masdil; Sweden: Cardizem; Coramil; Viazem; Switzerland: Coridil; Dilzem; Escozem; Tildiem; Ubicor¤; Thailand: Altiazem; Angizem; Cardil; Cascor; Denazox; Dilatam¤; Dilem; Dilizem; Diltan¤; Diltec; Dilzem; Ditizem; Herbesser; Medozem¤; Metazem¤; Mono-Tildiem¤; Tildiem¤; United Kingdom: Adizem; Angiozem¤; Angitil; Britiazim¤; Calazem¤; Calcicard; Dilcardia; Dilzem; Disogram; Horizem¤; Metazem¤; Optil; Slozem; Tildiem; Viazem; Zemtard; United States: Cardizem; Cartia; Dilacor; Dilt-XR; Diltia; Taztia; Tiamate¤; Tiazac; Venezuela: Acalix; Corazem; Cordisil; Daltazen; Presoquin; Tilazem
Multi-ingredient Preparations
Argentina: Lotrix¤; United Kingdom: Adizem-XL Plus¤; United States: Teczem
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