New Zealand - English - Medsafe (Medicines Safety Authority)
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New Zealand Data Sheet
Dilzem® 30 mg film coated tablets
Dilzem® 60 mg film coated tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Diltiazem hydrochloride 30 mg
Diltiazem hydrochloride 60 mg
Excipient(s) with known effect:
Dilzem tablets contain lactose. For the full list of excipients, see section 6.1.
Dilzem 30 mg tablet: a white, circular, film-coated, biconvex tablet of approximately 6mm
diameter embossed "D" one side.
Dilzem 60 mg tablet: a white capsule shaped, film-coated tablet, 10mm in length and 5mm wide;
with a breakline and ‘DL60’ engraved on one face.
Angina pectoris due to coronary artery spasm and chronic stable angina.
Dose and method of administration
Initially 30 mg three to four times daily increasing to 240 mg daily in divided doses. The
maximum recommended dose is 360 mg daily.
Pharmacokinetics of diltiazem in elderly patients has not been fully elucidated. Preliminary
results in elderly patients (over 65 years old) suggest that a lower dosage might be required in
this age group.
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Hepatic and renal impairment
There are few available data concerning dosage requirements in patients with impaired renal or
hepatic function. Dilzem should be used with caution in patients with hepatic or renal
impairment. If diltiazem must be used in these patients, the dosage should be carefully and
gradually adjusted depending on patient tolerability and responses.
Concomitant use with other cardiovascular agents
Sublingual glyceryl trinitrate may be taken as required to abort acute anginal attacks during
Dilzem may be safely co-administered with short- and long-acting nitrates.
Safety and efficacy in children aged has not been established. Therefore, diltiazem is not
recommended for use in children.
Method of Administration
Patients with sick-sinus syndrome except in the presence of a functioning ventricular
Patients with second or third degree AV block.
Patients with hypotension (< 90mmHg systolic).
Severe congestive heart failure or bradycardia.
Idiosyncrasy to diltiazem.
Special warnings and precautions for use
Cardiac Conduction: Caution is required in cases of first degree AV block. Diltiazem prolongs AV
node refractory periods but not sinus node recovery times (except in sick sinus syndrome). This
may result in slowing of heart rate, prolongation of the PR interval or even second or third
degree AV block. Concomitant use of diltiazem with beta-blockers or digitalis may result in
additive effects on cardiac conduction.
Congestive Heart Failure: Caution must be exercised in patients with congestive heart failure.
Hypotension: Arteriolar dilation produced by diltiazem administration may occasionally give rise
to symptomatic hypotension.
Acute Hepatic Injury: In rare instances, patients receiving diltiazem have exhibited reversible
acute hepatic injury as evidenced by moderate to extreme elevations of liver enzymes.
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Respiratory Events: The use of diltiazem may induce bronchospasm, including asthma
aggravation, especially in patients with pre-existing bronchial hyper-reactivity. Cases have also
been reported after dose increase. Patients should be monitored for signs and symptoms of
respiratory impairment during diltiazem therapy.
Concomitant Administration with Beta-Blockers: Diltiazem may cause marked prolongation of
atrioventricular conduction in a small number of patients, and caution is advised if combination
therapy is considered due to the risk of bradycardia. Such a combination should not be used in
patients with depressed left ventricular function and conduction system disease.
Abrupt Withdrawal: The sudden withdrawal of diltiazem has been associated with severe
Use in Diabetics: Diltiazem influences insulin secretion and peripheral action as a result of
inhibition of calcium influx into cells so caution is required if diltiazem is considered for use in
Use with Amiodarone: Caution is required if consideration is being given to the use of diltiazem
and amiodarone in combination especially in the presence of underlying dysfunction of the sinus
node such as bradycardia, sick sinus syndrome or partial AV block.
Concomitant Use with Digoxin: The combination of diltiazem with digitalis may give rise to
additive effects in prolonging AV conduction.
General: Diltiazem is extensively metabolised by the liver, metabolites being eliminated by the
kidneys and in bile. It should be used with caution & in reduced dosage in patients with impaired
renal or hepatic function. Liver function tests should be monitored during prolonged use as very
rare transaminase elevations have been noted.
Interaction with other medicines and other forms of interaction
The combination of diltiazem with beta-blockers may produce a positive clinical response in
patients with angina pectoris. Care is required, however, since AV conduction may be prolonged
leading to serious deleterious effects (See Warnings and Precautions). Diltiazem is known to
modify digoxin pharmacokinetics in healthy subjects, and in patients with cardiac insufficiency or
chronic atrial fibrillation.
These modifications involved: an increase in plasma digoxin concentration of 24-70%, a decrease
in mean renal digoxin clearance from 86.9 mL/min to 62.8 mL/min, and an increase in the mean
digoxin elimination half-life from 36.7 h to 44.5 h.
Concurrent administration of diltiazem with cimetidine results in an increase in both diltiazem
and desacetyl diltiazem plasma levels. Concomitant administration of diltiazem with diazepam
causes a significant decrease, averaging between 20-30%, in diltiazem plasma levels. The
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combination of diltiazem with amiodarone may have additive adverse effects on sinus node
function and myocardial contractility.
Chronic administration of diltiazem to patients on cyclosporin-A will result in increased trough
levels of cyclosporin-A.
Diltiazem HCl should not be administered with carbamazepine as two well-documented cases
have been reported where combination resulted in neurotoxicity.
A single case has been reported of cardiac arrhythmia involving sinus arrest and impaired AV
conduction after administration of enflurane and diltiazem together.
A single case has been reported of decreased insulin effect after combination treatment of
insulin and diltiazem although the mechanism was not established.
Concurrent use of diltiazem and sustained-release nitroglycerin preparations is to be avoided.
Care should be exercised initially if it is necessary to coadminister diltiazem and theophylline due
to possible toxicity.
Ingestion of grapefruit has been shown to increase the half-life of diltiazem as a result of
inhibition of gut wall metabolism of diltiazem during absorption. The clinical significance of this
is unknown. It is recommended that ingestion of grapefruit or grapefruit juice be avoided, or at
least do not take grapefruit/grapefruit juice within 10 hours before or two hours after taking
diltiazem 30 mg and 60 mg tablets.
Patients on diltiazem treated concomitantly with simvastatin 80 mg have a slightly increased risk
of myopathy. This is thought to be mediated through diltiazem inhibition of Cytochrome P 450
3A4 enzymes and the P-glycoprotein drug transporter leading to increased simvastatin plasma
levels. The risk of myopathy is approximately 1% in these patients. Treatment with simvastatin in
a patient taking diltiazem hydrochloride should be started at the lowest possible dose and
titrated upwards. If diltiazem hydrochloride treatment is to be added to patients already taking
simvastatin, consider a reduction in statin dose and retitrate against serum cholesterol
Fertility, pregnancy and lactation
There are no well-controlled studies of the use of diltiazem HCl in pregnant women. There is the
potential to produce foetal hypoxia associated with maternal hypotension therefore, diltiazem
HCl should only be used if the potential benefit justifies the potential risk to the foetus.
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Diltiazem HCl is excreted in human milk and breast milk concentrations may approximate serum
levels. Since the safety and effectiveness of diltiazem HCl in infants and children has not been
established an alternative method of infant feeding should be instituted if use of diltiazem HCl is
No data available.
Effects on ability to drive and use machines
Patients should be warned about the potential for dizziness and fatigue, and advised not to drive
or operate machinery if these symptoms occur or until their individual susceptibility is known.
Side effects are rare. The most common occurrences are: gastrointestinal discomfort with
nausea and vomiting, swelling and oedema, arrhythmia, headache and dizziness, rash and
fatigue. Mild to moderate elevation of alkaline phosphatase and transaminases occurs rarely.
The committee on safety of medicines in the U.K. has noted the following adverse effects:
serious skin reactions (exfoliative dermatitis and epidermal necrolysis), hypotension and one
case of agranulocytosis. Bradycardia and heartblock (sinoatrial &/or atrioventricular) have also
been noted as have muscular (including myalgia) effects and ocular (including abnormal vision)
Atrioventricular block is an uncommon but potentially serious adverse effect of diltiazem
treatment and the risk is increased by concurrent use of a beta-blocker.
Bronchospasm (including asthma aggravation) has also been reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows
continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are
asked to report any suspected reactions https://nzphvc.otago.ac.nz/reporting/
The oral LD
in mice and rats ranged from 415 to 740 mg/kg and from 560 to 810 mg/kg,
respectively. The intravenous LD
in these species was 60 and 38 mg/kg, respectively. The oral
in dogs is considered to be in excess of 50 mg/kg, while lethality was seen in monkeys at
360 mg/kg. The toxic dose in man is not known. Due to extensive metabolism, blood levels after
a standard dose of diltiazem can vary over tenfold, limiting the usefulness of blood levels in
overdose cases. There have been 29 cases of diltiazem overdose in doses ranging from less than
1 g to 10.8 g. Sixteen of these reports involved multiple drug ingestions. Twenty-two reports
indicated patients had recovered from diltiazem overdose ranging from less than 1 g to 10.8 g.
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There were seven reports with a fatal outcome; although the amount of diltiazem ingested was
unknown, multiple drug ingestions were confirmed in six of the seven reports.
The clinical effects of acute overdose can involve pronounced hypotension possibly leading to
collapse, sinus bradycardia with or without isorthythmic dissociation, heart block, cardiac
failure,and atrio-ventricular conduction disturbances. Most reports of overdose described some
supportive medical measure and/or drug treatment.
Bradycardia frequently responded favourably to atropine as did heart block, although cardiac
pacing was also frequently utilised to treat heart block. Fluids and vasopressors were used to
maintain blood pressure, and in cases of cardiac failure inotropic agents were administered. In
addition, some patients received treatment with ventilatory support, gastric lavage, activated
charcoal, and/or intravenous calcium. Evidence of the effectiveness of intravenous calcium
administration to reverse the pharmacological effects of diltiazem overdose was conflicting.
In the event of overdose or exaggerated response, appropriate supportive measures should be
employed in addition to gastrointestinal decontamination. Diltiazem does not appear to be
removed by peritoneal or haemodialysis.
For advice on the management of overdose please contact the National Poisons Centre on 0800
POISON (0800 764766).
Pharmacotherapeutic group: Calcium channel blocker, Benzothiazepine derivatives; ATC code:
Mechanism of action
Diltiazem, a benzothiazepine, is a calcium antagonist, inhibiting calcium ion entry into smooth
muscle cells by blockade of slow calcium channels. It is believed to act as follows:
Angina due to coronary artery spasm: Diltiazem is a potent dilator of both epicardial and
subendocardial coronary arteries and it inhibits spontaneous coronary artery spasm.
Exertional angina: Diltiazem is able to produce increases in exercise tolerance via reduction in
heart rate, systemic blood pressure and dilation of coronary arteries. In animal models diltiazem
interferes with the slow inward (depolarising) current in excitable tissue producing: relaxation of
coronary vascular smooth muscle, dilation of both large and small coronary arteries without
inducing a negative inotropic effect, and increased coronary blood flow accompanied by dose
dependent decreases in systemic blood pressure and peripheral resistance.
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Evaluation of glucose and lipid homeostasis in diabetic and non-diabetic subjects treated with
calcium antagonists indicates that diltiazem does not affect energy metabolism in the majority
Diltiazem is almost completely absorbed after oral administration but first pass metabolism
limits its systemic availability to about 50%. Although detectable in plasma between 30-60
minutes after administration, peak levels are normally achieved 2-4 hours after administration of
the 30 mg or 60 mg tablets.
Diltiazem is distributed to the liver, kidney, lung, spleen, heart and brain with tissue
concentration decreasing in that order. Plasma protein binding accounts for 77-86% of plasma
diltiazem, 35-40% being bound to albumin and the rest to a-glycoprotein.
Diltiazem is extensively metabolised in the liver by deacetylation, N-demethylation and O-
demethylation such that only 0.1-4% of unchanged diltiazem appears in the urine. Five
metabolites have been identified. Desacetyldiltiazem is normally present in plasma at levels of
10-20% of the parent medicine and is 25-50% as potent a vasodilator as diltiazem. Some studies
have, however, shown that this metabolite can accumulate during multiple oral dosing and the
plasma concentration may exceed that of the parent medicine. Another metabolite, N-mono-
demethyl-diltiazem may be about 20% as potent as the parent medicine. The other metabolites
are devoid of pharmacological activity.
Studies in rats have shown that after administration of
C-diltiazem, greater than 90% of the
can be removed from urine and faeces in 72 hours. Excretion of diltiazem metabolites in the
faeces seems to be the main route of elimination since more than 60% of the dose is excreted
into the bile in 24 hours and 65% into the faeces in 72 hours. There is extensive enterohepatic
The plasma half-life of diltiazem is approximately 3.5 hours. Therapeutic blood levels appear to
be in the range of 50-200 ng/mL.
Plasma levels above 50 ng/mL are achieved between 1-1.5 hours and are maintained for
approximately 8 hours after administration of the 30 mg and 60 mg tablets.
Little information is available as to the effect of age, renal or hepatic dysfunction on the
pharmacokinetic profile, other than that the more pronounced anti-hypertensive effect seen in
the elderly may be due to a decreased clearance.
Diltiazem hydrochloride is excreted in breast milk.
Preclinical safety data
Animal subacute toxicity and chronic toxicity studies in dogs and rats indicated hepatic damage
occurred at high dosages. Such damage was reversible when the drug was discontinued.
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Reproduction studies in mice, rats and rabbits showed administration of high doses resulted in
embryo and foetal deaths. Skeletal abnormalities were also observed. Peri-natal and post-natal
studies showed reduction in pup weights and survival rates with an increased incidence of still
The oral LD
in mice and rats ranges from 415-740 mg/kg and 560-810 mg/kg respectively. The
in both species is 60 mg/kg and 38 mg/kg respectively. The oral LD
in dogs is
considered to be in excess of 50 mg/kg. Lethality in monkeys was seen at 360 mg/kg. The toxic
dose in man is unknown, but blood levels in excess of 800 ng/mL have not been associated with
List of excipients
Dilzem tablets contain the following excipients:
Lactose, Cutina HR, Aluminium hydroxide gel dried, Eudragit NE30D, Talc, and Magnesium
stearate for the core and Opadry white (Y-IR-7000B) for coating.
Special precautions for storage
Store at or below 25°C.
Nature and contents of container
Bottles of 100, 500 or 1,000 tablets.
Blister packs of 30 tablets.
Not all strengths or pack sizes may be marketed.
Special precautions for disposal and other handling
No special requirements for disposal.
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Douglas Pharmaceuticals Ltd
P O Box 45 027
Phone: (09) 835 0660
DATE OF FIRST APPROVAL
Dilzem 30 mg: 10 April 1989
Dilzem 60 mg: 27 November 1986
DATE OF REVISION OF THE TEXT
1 November 2018
Summary table of changes
Summary of new information
Additional information on bronchospasm