DILATAM 120 SR

®

SR 120

®

!"#

CD

Diltiazem Hydrochloride 120 mg

Diltiazem Hydrochloride 240 mg

SR 120

Hydroxypropyl methylcellulose, povidone, colloidal silicon dioxide, hydrogenated vegetable oil,

magnesium stearate, hydroxypropyl cellulose, talc, polyethylene glycol 4000 and 6000.

CD 240

Hydroxypropyl methylcellulose, methacrylic acid copolymer, hydroxypropyl cellulose, talc, colloidal

silicon dioxide, hydrogenated vegetable oil, magnesium stearate, polyethylene glycol 4000 and 6000.

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dantrolene

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Dilatam 120 240 up 3/5/2012 AH/JO

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057 29 26825 00

067 47 26826 00

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ע עבקנ הז ןולע טמרופ

"

רשואו קדבנ ונכותו תואירבה דרשמ י

."

רשואמ ןולע

לירפא

2010

“This leaflet format has been determined by the Ministry of Health and the content thereof has been

checked and approved.” Date of approval: April 2010.

DILATAM

120 SR

SUSTAINED-RELEASE TABLETS

Composition

Each sustained-release tablet contains:

Active Ingredient

Diltiazem hydrochloride 120 mg

Other Ingredients:

Hydroxypropyl

methylcellulose,

povidone,

hydroxypropyl

cellulose,

talc,

polyethylene glycol, colloidal silicon dioxide, hydrogenated vegetable oil, magnesium

stearate.

Mechanism of Action

Dilatam 120 SR is a sustained-release tablet formulation offering the advantage of

twice daily administration.

Dilatam 120 SR is of particular importance for use in hypertension and angina

where it provides convenience and encourages patient compliance.

Diltiazem is a calcium antagonist (slow channel blocker) which inhibits the influx of

calcium ions during membrane depolarization of cardiac and vascular smooth muscle.

resultant

pharmacological

effects

cardiovascular

system

include

depression of mechanical contraction of the myocardial and smooth muscle, and

depression of both impulse formation (automaticity) and conduction velocity.

Diltiazem dilates the coronary arteries and arterioles, both in normal and ischemic

regions,

inhibits

coronary

artery

spasm.

This

increases

myocardial

oxygen

delivery in patients with vasospastic (Prinzmetal's or variant) angina.

Although diltiazem rarely produces clinically important changes in the rate of

sinoatrial (SA) node discharge or recovery time, the drug usually reduces the resting

heart rate slightly, especially in patients with SA node disease (e.g. sick sinus

syndrome). Diltiazem also slows atrioventricular (AV) node conduction and prolongs

refractoriness, thereby prolonging the AH (Atria-His bundle) interval. This usually

results in PR prolongation on ECG and may rarely cause second- or third-degree AV

block.

Dilatam 120 SR produces antihypertensive effects both in the supine and standing

positions. Postural hypotension is infrequently noted upon suddenly assuming an

upright position. No reflex tachycardia is associated with the chronic antihypertensive

effects. Dilatam 120 SR decreases vascular resistance, increases cardiac output (by

increasing stroke volume) and produces a slight decrease or no change in heart rate.

During dynamic exercise, increases in diastolic pressure are inhibited while maximum

achievable systolic pressure is usually reduced. Heart rate at maximum exercise does

not change or is slightly reduced. Chronic therapy with diltiazem produces no change

increase

plasma

catecholamines.

increased

activity

renin-

angiotensin-aldosterone axis has been observed. Dilatam 120 SR antagonizes the

renal and peripheral effects of angiotensin II.

DILATAM 120 SR, 14. 4. 2010, RH

Indications

Hypertension

Dilatam 120 SR may be used either as monotherapy or with other antihypertensive

medications such as diuretics.

Angina Pectoris

- Chronic stable angina.

- Angina due to coronary artery spasm.

Contraindications

Known hypersensitivity to the drug or to any other ingredient of the preparation..

Pregnancy and women of childbearing capacity.

Breastfeeding.

Sick sinus syndrome or second or third degree AV block, except in the presence of a

functioning ventricular pacemaker.

Hypotension (less than 90 mm Hg systolic).

Congestive heart failure.

Sever bradycardia (below 40 beats per minute).

Left ventricular failure with pulmonary congestion.

Acute myocardial infarction and pulmonary congestion, documented by X-ray on

admission.

Concurrent use with dantrolene infusion because of the risk of ventricular fibrillation

(see Drug Interactions)

Warnings

Hypotension

Decreases in blood pressure associated with diltiazem therapy may occasionally

result in symptomatic hypotension.

Congestive Heart Failure

Although diltiazem has a negative inotropic effect in vitro, hemodynamic studies in

humans with normal ventricular function have not shown a reduction in cardiac index

or consistent negative effects on contractility.

Worsening of congestive heart failure has been reported in patients with preexisting

impairment of ventricular function. Experience with the use of diltiazem in combination

with

-blockers in patients with impaired ventricular function is limited. Caution should

be exercised when using this combination.

Cardiac Conduction

Close observation is necessary in patients with reduced left ventricular function,

bradycardia (risk of exacerbation) or with a first degree AV block detected on the

electrocardiogram (risk of exacerbation and rarely, of complete block).

Diltiazem prolongs AV node refractory periods without significantly prolonging sinus

node recovery time, except in patients with sick sinus syndrome. This may rarely

result

abnormally

slow

heart

rates

(particularly

patients

with

sick

sinus

syndrome), or second or third degree AV block (0.4%). A patient with Prinzmetal's

angina developed periods of asystole (2-5 seconds) after a single dose of 60 mg

diltiazem. Concomitant use of diltiazem with

-blockers or digitalis may result in

additive effects on cardiac conduction.

DILATAM 120 SR, 14. 4. 2010, RH

Acute Hepatic Injury

In rare instances, symptoms consistent with acute hepatic injury including significant

elevations

enzymes

such

alkaline

phosphatase,

creatinine

phosphokinase

(CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine

aminotransferase (ALT), have occurred with diltiazem. These were reversible on drug

discontinuation.

Drug relationship was uncertain in most cases, but probable in some.

These laboratory abnormalities have rarely been associated with clinical symptoms;

however cholestasis, with or without jaundice, has been reported. Rare instances of

allergic hepatitis have been reported.

Carcinogenesis, Mutagenesis, Impairment of Fertility.

A 24-month study in rats at oral dosage levels of up to 100 mg/kg/day and a 21-

month study in mice at oral dosage levels of up to 30 mg/kg/day showed no evidence

of carcinogenicity. There was also no mutagenic response in vitro or in vivo in

mammalian cell assays or in vitro in bacteria. No evidence of impaired fertility was

observed in a study performed in male and female rats at oral dosages of up to

100mg/kg/day.

Use in Pregnancy

(see Contraindications)

Reproduction studies have been conducted in mice, rats and rabbits. Administration

doses

ranging

from

5-10

times

greater

mg/kg

basis)

than

daily

recommended therapeutic dose has resulted in embryo and fetal lethality. In some

studies, these doses have been reported to cause skeletal abnormalities. In peri- and

post-natal studies, there was some reduction in early pup weights and survival rates.

There was an increased incidence of stillbirth at doses of 20 times the human dose or

greater.

There are no well-controlled studies in pregnant women. . Also, dilitazem is a

calcium channel blocker and drugs listed in this class carry the potential for fetal

hypoxia aswsociated with maternal hypotension. Therefore, diltiazem must not be

used in pregnancy or women of childbearing potential.

Use in Breastfeeding

(see Contraindications)

Diltiazem is excreted in human milk. Diltiazem levels were measured in both serum

and milk in lactating women. One report suggests that concentrations in breast milk

may approximate serum levels. These data show that diltiazem is freely diffusible in

milk but it is not known whether it is harmful to the newborn. Therefore, breastfeeding

while taking this drug should be avoided.

Use in Pediatrics

Safety and efficacy of the use of diltiazem in children have not been established.

Use in the Elderly

The half life of calcium channel blockers may be increased in the elderly as a result

of decreased clearance. Therefore caution should be exercised in this patient group.

Increase in plasma concentrations may be associated with increase in incidence of

adverse reactions (approximately 13% higher in this group). Those adverse reactions

which occur more frequently include: peripheral oedema, bradycardia, palpitation,

dizziness, rash and polyuria.

DILATAM 120 SR, 14. 4. 2010, RH

Impaired Renal Function

Although the pharmacokinetic profile of diltiazem in patients with impaired renal

function is similar to that in patients with normal renal function, caution is still advised.

Impaired Hepatic Function

Since diltiazem is extensively metabolized by the liver, it should be used with

caution in patients with impaired hepatic function or reduced hepatic blood flow.

Dosing reduction may be necessary.

Adverse Reactions

Adverse reactions are generally not serious and rarely require discontinuation of

therapy

dosage

adjustment.

clinical

trials

diltiazem

diltiazem

formulations involving over 3200 patients, the most common events (i.e, greater than

1%) were edema (4.6%), headache (4.9% ), dizziness (3.5%), asthenia (2.7%), first

degree AV block (2.2%), bradycardia (1.6%), flushing (1.5%), nausea (1.4%), rash

(1.3%), dyspepsia (1.2%), palpitations, lower limb oedema, constipation, gastric pain,

malaise and erythema.

In addition, the following events were reported infrequently (less than 1%) in angina

or hypertension trials.

Cardiovascular System

Peripheral edema, hypotension, palpitations, syncope, AV block (1st, 2nd or 3rd

degree), bradycardia, congestive heart failure, arrhythmia (unspecified), pulmonary

edema, angina, tachycardia, abnormal ECG, ventricular extrasystoles.

Central Nervous System

Dizziness,

lightheadedness,

nervousness,

sleep

disturbances,

psychiatric

disturbances (depression, amnesia, paranoia, psychosis, hallucinations, personality

changes),

headache,

weakness,

shakiness,

jitteriness,

paresthesia,

somnolence,

asthenia, insomnia, abnormal dreams, tinnitus, tremor/hand tremor.

Gastrointestinal

Anorexia, nausea, diarrhea, constipation, abdominal discomfort, abdominal cramps,

dyspepsia, disgeusia, hepatic enzyme increase (AST, ALT, LDH, ALP), vomiting, dry

mouth, thirst, weight increase..

Dermatological

Dermatitis, rash, pruritus, urticaria, hair loss, photosensitivity, erythema multiforme,

Stevens-Johnson syndrome.

Hematopoietic

Leukopenia, petechiae, ecchymosis, purpura, bruising, hematoma.

Other

Flushing, nasal congestion, chest congestion, sinusitis, rhinitis, gingival hyperplasia,

micturition disorders (e.g. polyuria, nocturia, dysuria), sexual difficulties, impotence,

shortness of breath, dyspnea, wheezing, joint stiffness, pain, arthritis, gynecomastia,

hyperglycemia, hyperuricemia, weight gain, epistaxis, anorexia, muscle cramps, CPK

increase, osteoarticular pain.

DILATAM 120 SR, 14. 4. 2010, RH

In addition to the adverse effects listed above, the following have been reported:

gait abnormality, tremor, amblyopia, eye irritation, bundle branch block, and amnesia.

The following postmarketing events have been reported infrequently in patients

receiving

diltiazem:

mood

changes

(including

deprerssion),

sino-atrial

block,

congestive heart failure, photosensitivity, hepatitis, musculo-cutaneous reactions such

as simple erythema or occasionally desquamative erythema with or without fever,

angioneurotic edema, symptoms of vasodilation (such as flushing, lower limb edema,

sweating), alopecia, erythema multiforme (including rare cases of Steven-Johnson's

syndrome),

exfoliative

dermatitis,

extrapyramidal

symptoms,

acute

generalized

exanthematous pustular dermatitis, orthostatic hypotension, malaise, gastric pain,

gingival hyperplasia, hemolytic anemia, increased bleeding time, leukopenia, purpura,

retinopathy and thrombocytopenia. Very rare cases of toxic epidermal necrolysis have

also been reported In addition, events such as myocardial infarction have been

observed which are not readily distinguishable from the natural history of the disease

these

patients.

number

well-documented

cases

generalized

rash,

characterized as leukocyloclastic vasculitis, have been reported. However, a definitive

cause and effect relationship between these events and diltiazem therapy is yet to be

established.

Precautions

Diltiazem is extensively metabolized by the liver and excreted by the kidneys and in

bile. As with any drug given over prolonged periods, laboratory parameters of renal

and hepatic function should be monitored at regular intervals.

Dermatological Events

Dermatological events may be transient and may disappear despite continued use

of diltiazem. However, skin eruptions progressing to erythema multiforme and/or

exfoliative dermatitis have also been infrequently reported. Should a dermatologic

reaction persist, the drug should be discontinued.

Use in Diabetics

Diltiazem should be used with caution in patients suffering from diabetes. Like other

calcium channel blockers, diltiazem influences insulin secretion and its peripheral

action by inhibiting calcium influx into cells. In one study, increases in fasting and

peak glucose levels were observed after 2 to 6 months of diltiazem administration.

Other Effects

Calcium channel blocking agents, such as diltiazem, may be associated with mood

changes, including depression.

Like

other

calcium

channel

antagonists,

diltiazem

inhibitory

effect

intestinal motility. Therefore, it should be used with caution in patients at risk to

develop an intestinal obstruction.

Abrupt Withdrawal

The sudden withdrawal of dilitazem has been associated with sever angina in

anginal patients.

Effects on Ability to Drive and Use Machines

Diltiazem

cause

adverse

reactions

such

dizziness,

which

impair

patients' ability to drive or operate machinery to a varying extent depending on the

dosage and individual susceptibility. Therefore, patients should not drive or operate

machinery if affected.

DILATAM 120 SR, 14. 4. 2010, RH

Drug Interactions

Note:

Due to the potential for additive effects, caution and careful titration are warranted in

patients receiving diltiazem concomitantly with other agents known to affect cardiac

contractility and/or conduction.

Diltiazem is extensively metabolised by CYP3A4, and as a result serum levels of

diltiazem may be:

Increased by concomitant usage of CYP3A4 inhibitors such as H2 antagonists (e.g.

cimetidine, ranitidine) and protease inhibitors (e.g. atazanavir, ritonavir)

Decreased

concomitant

usage

CYP3A4

inducers

such

barbiturates

(phenobarbital, primidone), phenytoin and rifampicin.

Diltiazem is also an inhibitor of CYP3A4, and may therefore increase serum levels

CYP3A4

substrates

such

benzodiazepines

(especially

midazolam

triazolam), carbamazepine, ciclosporin, cilostazol, ivabradine, statins (simvastatin,

atorvastatin,

lovastatin),

sirolimus,

tacrolimus

theophylline.

Care

should

exercised in patients taking these drugs. Concomitant use of diltiazem with cilostazol

and ivabradine should be avoided.

Diltiazem

-adrenergic Blockers/Calcium Channel Blockers:

-adrenergic blockers and

calcium channel blockers both have negative chronotropic and inotropic effects.

These combinations are advantageous in some patients (e.g. hypertension, angina);

however, they may be a problem in others (e.g. sinoatrial disease, conduction defects,

heart failure) (see Warnings).

Combination therapy can, however adversely affect cardiac function, because of

the depressant effects on myocardial contractility or AV conduction. Therefore, if

combined therapy is used, closely monitor the patient and reassess continued use

periodically Patients with pre-existing conduction defects should not receive the

combination of diltiazem and beta-blockers.

Administration of diltiazem concomitantly with propranolol in five normal volunteers

resulted

increased

propranolol

levels

subjects

bioavailability

propranolol was increased by approximately 50%. If combination therapy is initiated or

withdrawn in conjunction with propranolol, an adjustment in the propranolol dose may

be warranted.

In contrast, there appears to be no effect on the pharmacokinetics of atenolol, a

renally cleared drug. In view of the known pharmacodynamic interactions between

these classes of drugs, this effect may be of clinical relevance.

Dilitazem/Drugs

which

Induce

Bradycardia/Other

Antiarrhy hmic

Drugs

(e.g.

Amiodarone):

There may be an additive effect (increased depression of cardiac conduction with

risk of bradycardia and AV block) when diltiazem is prescribed with drugs which may

induce

bradycardia

other

anti-arrhythmic

drugs

(e.g.

amiodarone

beta

blockers).

Amiodarone should be used with caution with diltiazem particularly if there is

suspicion of underlying dysfunction of the sinus node, such as bradycardia or sick

sinus syndrome or if there is partial A-V block. Sinus arrest and a life-threatening low

cardiac output state developed when amiodarone was added to a regimen of diltiazem

and a diuretic. It has been suggested that diltiazem and amiodarone have additive

adverse effects on sinus node function and myocardial contractility. There is an

increased

risk

bradycardia

with

this

combination.

Caution

required

when

amiodarone is combined with diltiazem, particularly in the elderly and when high

doses are used.

DILATAM 120 SR, 14. 4. 2010, RH

Diltiazem/Rifampicin

: There is a risk of decreased diltiazem plasma levels after

initiating therapy with rifampicin. The patient should be carefully monitored when

initiating or discontinuing rifampicin treatment.

Diltiazem/Benzodiazepines

(e.g.

Midazolam,

Triazolam,

Diazepam):

Diltiazem

significantly increases plasma concentration of midazolam and triazolam and prolongs

their

half-life.

Special

care

should

taken

when

prescribing

short-acting

benzodiazepines metabolised by the CYP3A4 pathway in patients using diltiazem.

Diazepam has been reported to cause a significant decrease in diltiazem plasma

levels. The average decrease in diltiazem concentration was between 20 and 30%.

Three out of eight patients showed decreases which were greater than 50%.

Diltiazem/Buspirone

: In 9 healthy subjects, diltiazem significantly increased the mean

buspirone AUC 5.5-fold and Cmax 4.1-fold compared to placebo. The T

and T

buspirone

were

significantly

affected

diltiazem.

Enhanced

effects

increased toxicity of buspirone may be possible during concomitant administration

with

diltiazem.

Subsequent

dose

adjustments

necessary

during

administration, and should be based on clinical assessment

Dilitazem/ Corticosteroids (e.g Methyprednisolone):

Concomitant administration has

resulted in the inhibition of methylprednisolone metabolism (CYP3A4) and inhibition of

P-glycoprotein. The patient should be monitored when initiating methylprednisolone

treatment. An adjustment in the dose of methylprednisolone may be necessary

Diltiazem/Alpha Blockers:

Concomitant treatment with alpha-blockers may produce or

aggravate hypotension. The combination of diltiazem with an alpha-blocker should

only be considered with the strict monitoring of blood pressure due to the risk of

increased antihypertensive effects.

Diltiazem/Rimonabant

: Co-administration with diltiazem results in an increase in serum

rimonabant levels.

Diltiazem/Short and Long Acting Nitrates

: Increased hypotensive effects and faintness

may be seen due to additive vasodilatating effects. In patients treated with calcium

channel antagonists, the addition of nitrate derivatives should only be carried out at

gradually increasing doses.

Diltiazem/Phenobarbital/Phenytoin

: As with all drugs, care should be exercised when

treating patients with multiple medications. Diltiazem undergoes biotransformation by

cytochrome P450 mixed function oxidase. Coadministration of diltiazem with other

agents which follow the same route of biotransformation may result in the competitive

inhibition of metabolism. Dosages of similarly metabolized drugs, particularly those of

low therapeutic ratio, or in patients with renal and/or hepatic impairment, may require

adjustment when starting or stopping concomitantly administered diltiazem, in order to

maintain optimum therapeutic blood levels.

Diltiazem/Quinidine/Theophylline/Carbamazepine

Pharmacologic

effects

increased due to inhibition of hepatic metabolism possibly by diltiazem. The increased

plasma levels cause neurotoxic symptoms which resolve several days after stopping

the calcium blocker. Concomitant administration of diltiazem with carbamazepine has

been reported to result in elevated serum levels of carbamazepine (40% to 72%

increase) resulting in toxicity in some cases.

Diltiazem/Tricyclic

Antidepressants

Diltiazem

increase

bioavailability

tricyclic antidepressants.

Diltiazem/Cimetidine/Ranitidine

: Cimetidine or ranitidine increase the bioavailability of

diltiazem. Patients on diltiazem should be monitored closely when adding cimetidine

or ranitidine and, if necessary, the dose of diltiazem should be reduced.

DILATAM 120 SR, 14. 4. 2010, RH

Diltiazem/Statins

Diltiazem

inhibitor

CYP3A4

been

shown

significantly

increase

some

statins.

risk

myopathy

rhabdomyolysis

statins

metabolised

CYP3A4

increased

with

concomitant use of diltiazem. When possible, a non CYP3A4-metabolised statin

should be used together with diltiazem, otherwise close monitoring for signs and

symptoms of a potential statin toxicity is required.

Diltiazem/Cyclosporin

: Cyclosporin plasma levels may be increased by diltiazem, and

renal toxicity may occur. Therefore, cyclosporine concentrations should be monitored,

especially when diltiazem therapy is initiated, adjusted, or discontinued.

Diltiazem/Lithium

: Diltiazem and lithium appear to act synergistically. Neurotoxicity

has occurred with coadministration, even when the lithium level was in the therapeutic

range.

Diltiazem/Digoxin

Serum

digoxin

levels

increased

upon

concomitant

administration

calcium

channel

blockers

digoxin.

Although

some

studies

suggest that no significant interaction occurs with diltiazem, caution is required and

digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem

therapy to avoid possible over or underdigitalization.

Diltiazem/Anticoagulants/Aspirin/Salicylates

: Anticoagulants, aspirin and salicylates

highly

protein-bound

drugs.

Caution

should

exercised

upon

concomitant

administration with diltiazem, since serum levels of these agents may be increased.

Diltiazem/Antihypertensive Agents (e.g.: ACE Inhibitors)

Alcohol

: Additive hypotensive

effects may result upon concomitant administration. Therefore, caution should be

exercised, and dosage adjustments of either agents may be necessary.

Diltiazem/Inhalation Anesthetics

: Concurrent use with calcium channel blockers may

produce additive hypotensive effects. Therefore, caution should be exercised when

inhalation anesthetics are administered during surgery, to patients on dialtiazem.

Diltiazem/Encainide

: Serum encainide levels may be increased without any change in

the levels of the active metabolites of encainide.

Diltiazem/Fentanyl

: Severe hypotension or increased fluid volume requirements have

occurred in patients receiving nifedipine and fentanyl concomitantly; this interaction

should also be considered for all calcium blockers.

Diltiazem/Dantrolene Infusion

: Lethal ventricular fibrillation is regularly observed in

animals when intravenous verapamil and dantrolene are administered concomitantly.

combination

calcium

channel

antagonist

dantrolene

therefore

potentially dangerous.

Dosage and Administration

Note: Dilatam 120 SR Tablets are not suitable for use in patients who require less

than 120 mg per dose, since the tablet is not divisible.

Hypertension

The usual recommended dosage of Dilatam 120 SR Tablets is one tablet twice

daily. The dosage should be individualized and adjusted to the patient's needs.

The maximum antihypertensive effect is achieved usually by 14 days of chronic

therapy. The usual optimum dosage range reported in clinical trials was 240-360

mg/day.

Angina Pectoris

The usual recommended dosage of Dilatam 120 SR Tablets is one tablet twice

daily. The dosage should be individualized and adjusted to the patient's needs.

DILATAM 120 SR, 14. 4. 2010, RH

Concomitant Drug Therapy

An additive antihypertensive effect occurs when diltiazem is coadministered with

other antihypertensives. Adjust the dose of Dilatam 120 SR or the concomitant

antihypertensive accordingly.

Sublingual nitroglycerin may be taken as required to abort acute anginal attacks

during Dilatam 120 SR therapy. Dilatam 120 SR may be also coadministered with

prophylactic nitrate therapy.

Overdosage

The oral LD50 in mice and rats ranged from 415 to 740 mg/kg and from 560 to 810

mg/kg, respectively. The intravenous LD50 in these species was 60 and 38 mg/kg,

respectively. The oral LD50 in dogs is considered to be in excess of 50 mg/kg, while

lethality was seen in monkeys at 360 mg/kg. Toxic diltiazem blood levels in man are

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. 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

Manifestations

Nausea, weakness, dizziness, drowsiness, confusion, and slurred speech. Marked

and prolonged hypotension (possibly leading to collapse) and bradycardia (with or

without isothythmic dissociation), both of which may result in decreased cardiac

output. Junctional rhythms and second- or third-degree AV block, , cardiac failure, and

atrioventricular conduction disturbances may be seen. Death has occurred.

Treatment

If the patient is seen shortly after oral ingestion, employ emetics or lavage and

cathartics. Treatment is supportive.

-adrenergic agents or IV calcium have been

used effectively. Although calcium appears to reverse adverse hemodynamic effects,

it may not always reverse electrophysiological toxicity. Cardiac failure is treated with

inotropic agents (isoproterenol, dopamine or dobutamine) and diuretics.

Monitor

cardiac

respiratory

function.

patients

with

hypertrophic

cardiomyopathy

(IHSS),

-adrenergic

agents

(phenylephrine

hydrochloride,

metaraminol

bitartrate

methoxamine

HCl)

maintain

blood

pressure;

avoid

isoproterenol and norepinephrine. Since these agents are highly protein bound,

dialysis is not likely to help.

The following are treatment guidelines for acute cardiovascular adverse reactions:

Symptomatic Hypotension Requiring Treatment

Primary treatment (by IV route) consists of dopamine, norepinephrine, metaraminol,

isoproterenol or calcium . Supportive treatment consists of IV fluids administered in

the Trendelenburg position.

DILATAM 120 SR, 14. 4. 2010, RH

DILATAM 120 SR, 14. 4. 2010, RH

Bradycardia, AV Block, Systole

Primary treatment (by IV route) consists of isoproterenol or norpinephrine (not in

patients with IHSS), atropine sulfate,(0.6-1 mg) calcium gluconate (10% solution),

and, in addition, cardiac pacing. Supportive treatment consists of IV fluids (slow drip).

Rapid Ventricular Rate Due to Antegrade Conduction in Flutter/Fibrillation with Wolff-

Parkinson-White or Lown-Ganong-Levine Syndromes

Primary treatment consists of DC cardioversion and procainamide or lidocaine (by

IV route). Supportive treatment consists of IV fluids (slow drip).

Storage

Store in a dry and dark place, below 25

Registration Number

057.29.26825.00

Manufacturer

Teva Pharmaceutical Industries Ltd

P.O.Box 3190, Petach Tikva

Abic Ltd

P.O.Box 8077, Kiryat Nordau, Netanya