DTZ

Main information

  • Trade name:
  • DTZ Capsules Modified Release 180 mg Milligram
  • Dosage:
  • 180 mg Milligram
  • Pharmaceutical form:
  • Capsules Modified Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DTZ Capsules Modified Release 180 mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0915/005/002
  • Authorization date:
  • 07-09-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DTZ180mg Prolonged-ReleaseCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each capsulecontainsDiltiazem(asHydrochloride)180mg in aprolonged releaseformulation.

3PHARMACEUTICALFORM

Aprolonged releasecapsule(size1), hard with naturaltransparentcap, and opaquepink body with themarking‘DTZ

180’imprinted, containing white-grey to lightyellowalmostsphericalpellets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Mild to moderatehypertension.

4.2Posologyandmethodofadminstration

Adults

Hypertension:240 mg oncedaily.Dosagetitration in 60mg to 120mg stepsat2-weekly intervalsmay berequired to

obtain satisfactory clinicalresponse(240mg to 360mg daily willusuallysuffice).

Dosageshould bereduced in thepresenceofadversereactionsorifthepulseratefallsbelow50 perminute.

Elderlyandpatientswithimpairedhepaticorrenalfunction

Hypertension:Starting dose120 mg oncedaily.

Children

Notrecommended.

4.3Contraindications

1. DTZshould notbeused in patientswith aknown hypersensitivity to any oftheingredients.

Usein pregnancy and in women ofchildbearing potential.

‘DTZ’depressesatrioventricularnodeconduction and isthereforecontraindicated in patientswith marked

bradycardia, sick sinussyndrome, uncontrolledheartfailureorsecond orthird degreeAVblock.

4.4Special warningsandspecialprecautionsforuse

‘DTZ’should beused with caution in patientswith reduced leftventricularfunction.Patientswith mildbradycardia,

and/orhaving aprolonged PRinterval, should beobserved closely.

Patientswith rarehereditary problemsoffructoseintolerance, glucosemalabsorption orsucrase-isomaltase

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

In common with othercalciumantagonists, when‘DTZ’isused with drugswhich may inducebradycardia(e.g.

amiodaroneand beta-blockers)orwith otherantihypertensivedrugs, thepossibility ofan additiveeffectshould be

bornein mind.

Diltiazemhasbeen used safely in combination with beta-blockers, diuretics, ACEinhibitorsand otherantihypertensive

agents.Itisrecommended thatpatientsreceiving thesecombinationsshould beregularly monitored.Concomitantuse

with alpha-blockerssuch asprazosin should bestrictly monitored becauseofthepossiblemarked synergistic

hypotensiveeffectofthiscombination.

Casereportshavesuggestedthatbloodlevelsofcarbamazepine,cyclosporinandtheophyllinemaybeincreasedwhen

givenconcurrentlywithdiltiazemhydrochloride.Careshouldbeexercisedinpatientstakingthesedrugs.Incommon

with othercalciumantagonists, diltiazemmay causesmallincreasesin plasmalevelsofdigoxin.

In patientstaking H

receptorantagonistsconcurrently with‘DTZ’,increased levelsofDiltiazemmay beproduced.

Diltiazemhydrochloridetreatmenthasbeen continued withoutproblemduringanaesthesia, buttheanaesthetistshould

beinformed thatthepatientisreceiving acalciumantagonist.

4.6Pregnancyandlactation

Diltiazemhydrochlorideisteratogenicin someanimalspecies.In theabsenceofadequateevidenceofsafety in human

pregnancy‘DTZ’should notbeused in pregnancy orin women ofchild bearing potential.

Nursing mothers:Diltiazemhydrochlorideisexcreted in breastmilk. Onereportsuggeststhatconcentrationsin breast

milk reach similarlevelsto thosein serum.Ifuseof‘DTZ’isconsideredessential, an alternativemethod ofinfant

feeding should beinstituted.

4.7Effectsonabilitytodriveandusemachines

Theproductisassumed to besafeand unlikely to produceaneffecton ability to driveandusemachines.

4.8Undesirableeffects

Thefollowing undesirableeffectshavebeen reported:ankleoedema, malaise, headache, hotflushes, gastro-intestinal

disturbancesand very rarely, symptomaticbradycardia, sino-atrialblock and atrio-ventricularblock.Rash hasbeen

reported in association with diltiazem.

Thesereactionsaregenerallymild and resolveon cessation oftherapy, however, severevascularskin reactionshave

been reported occasionally.

Isolated casesofmoderateand transientelevation oflivertransaminaseshavebeen observedatthestartoftreatment.

Isolated casesofclinicalhepatitishavebeen reported which resolved on cessation oftherapy.

Thecurrentliteraturesuggeststhattheeffectsofvasodilation, particularly ankleoedema, aredosedependentand are

morefrequentin theelderly.

4.9Overdose

Signsand symptoms:Acuteintoxication can lead to severehypotension, bradycardia, firstto third degree

atrioventricularblock and, on occasion, to cardiacarrest.Hyperglycaemiamay requiretreatment.Onsetofsymptoms

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Treatment:Observation in acoronary orintensivecareunitisadvisableifasubstantialoverdosehasbeen ingested.

Soon afteringestion, gastriclavagefollowed by 50to 100 mg activated charcoalmay reduceabsorption.Profound

hypotension requiresplasmaexpanders, IVcalciumgluconateand inotropicagents(e.g. dopamine, dobutamineor

isoprenaline).

Symptomaticbradycardiaand heartblock may respond to atropine, isoprenalineor, ifnecessary, cardiacpacing.

‘DTZ’areextended releasecapsulesandeffectsmay beslowin onsetand prolonged.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup

Diltiazemhydrochlorideisacalciumantagonist.

MechanismofAction

Diltiazemselectively reducescalciumentry through voltage-dependantcalciumchannelsinto vascularsmooth muscle

cellsand myocardialcells.Thislowerstheconcentration ofintracellularcalciumwhich isavailableto activate

contractileproteins.In vasculartissue, diltiazemrelaxesarterialsmooth muscle, reducing systemicperipheral

resistanceand dilating thecoronary arteries.In cardiacmuscle, diltiazemreducescontractility and slowstheheartrate

through itsnegativechronotropicand inotropicactions.Cardiacwork andoxygen demand can thereforebereduced

withoutreflex tachycardia.

5.2Pharmacokineticproperties

(a) GeneralCharacteristicsoftheActiveSubstance(s)

Diltiazemiswellabsorbed fromthegastrointestinaltractand issubjectto an extensivefirstpasseffect, givingan

absolutebioavailability (compared to intravenousadministration)ofabout40%.

DTZisabout80-85%plasmaprotein bound.Plasmalevelsabove40-50 ng/mLareassociated with pharmacological

activity.

Diltiazemisextensively metabolisedby theliver, theplasmahalflifebeing on average3-4.5 hours.

Thetwo majoractivecirculating metabolites, desacetyldiltiazemand N-monodemethyldiltiazem, possesscoronary

artery vasodilatory activity equivalentto about50%ofthatofdiltiazem.Only 0.2 to 4%ofdiltiazemisfound

unchanged in theurine.

Thesustained releasepelletsin thispresentation usually achievemaximumplasmadiltiazemlevelssix to eighthours

afterdosing and haveaplasmaelimination halflifeofapproximately 7 hours, allowing oncedaily dosing.

Thebioavailability ofdiltiazemfromthe‘DTZ’formulation given onceaday isequivalentto thatobtained froma

conventionalreleasetabletgiven threetimesaday, when thesametotaldaily doseisadministered.

(b) Characteristicsinpatients

Datafromstudiesin patientsand healthy volunteershavealso demonstrated thattrough plasmalevels(i.e. 24 hours

postdosing)can bemaintained within theminimumtherapeuticrangeby appropriatedosetitration.

Plasmaconcentrationsinelderly patientsand in hepaticfailurearein generalhigherthan in young subjects, dueto an

increasein apparentbioavailability.In renalfailure, areduction in dosageisonly necessary asafunction oftheclinical

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5.3Preclinical safetydata

No findingshavebeen reported frompre-clinicalsafety studieswhich add to theprescribinginformation given in other

sections.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sucrose

Maizestarch

Povidone

Shellac

Ethylcellulose

Talc

Erythrosin E127

Indigotin E132

TitaniumdioxideE171

Gelatin

Black iron oxide(E172)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

3 years.

6.4Special precautionsforstorage

Do notstoreabove25°C.

6.5Natureandcontentsofcontainer

Blisterpackagescomprising heat-sealablePVC/PVdCand aluminiumfoil.Blistersizesare4, 28 and 56 capsulesin a

cardboard carton.

Notallpack sizesmay bemarketed.

6.6Instructionsforuseandhandling

No specialrequirements

7MARKETINGAUTHORISATIONHOLDER

Helsinn Birex TherapeuticsLimited,

Damastown,

Mulhuddart,

Dublin 15.

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8MARKETINGAUTHORISATIONNUMBER

PA915/5/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 7 th

September1999

Dateoflastrenewal: 7 th

September2004

10DATEOFREVISIONOFTHETEXT

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