DILTIAZEM HYDROCHLORIDE TABLETS 60 MG (PROLONGED RELEASE).

Main information

  • Trade name:
  • DILTIAZEM HYDROCHLORIDE TABLETS 60 MG (PROLONGED RELEASE).
  • Dosage:
  • 60 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DILTIAZEM HYDROCHLORIDE TABLETS 60 MG (PROLONGED RELEASE).
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0405/030/001
  • Authorization date:
  • 18-12-1990
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DiltiazemHydrochlorideTablets60mg(Prolongedrelease).

2QUALITATIVEANDQUANTITATIVECOMPOSITION

ActiveConstituent mg/tablet

DiltiazemHydrochloride 60mg

Excipients:Lactosemonohydrate 260mg

Forafulllistofexcipients,seeSection6.1.

3PHARMACEUTICALFORM

Prolongedreleasetablet.

Prolongedreleaseconvexwhitetabletwith“DT/60”ononesideand“G”onthereverse,approximately10mmin

diameterandapproximately5mminthickness.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Intheprophylaxisandtreatmentofanginapectorisandhypertension.

4.2Posologyandmethodofadministration

Adults

Theinitialdoseis60mgthreetimesdaily.Patientresponsescanvaryanddosagemaybeincreasedto360mgdailyin

divideddosesifrequired.Higherdosesupto480mgperdayhavebeenusedwithbenefitinsomepatients,especially

inunstableangina.Thereisnoevidenceofanydecreaseinefficacyatthesehigherdoses.

Elderlyandpatientswithimpairedhepaticorrenalfunction

Dosageshouldcommenceatthelowerlevelof60mgtwicedailyandbeincreasedslowly.Monitoringoftheheartrate

maybecarriedout.Thedoseshouldnotbeincreasediftheheartratefallsbelow50beatsperminute.

Children

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4.3Contraindications

Useinpregnancyandwomenofchildbearingcapacity,(seeSection4.6).

Diltiazemdepressesatrioventricularnodeconductionandshouldnotbeusedinpatientswithseverebradycardia

(lessthan50b.p.m.);hypotension(lessthan90mmHgsystole)leftventricularfailurewithstasis;secondorthird

degreeheartblockexceptinthepresenceofafunctioningpacemakerorsicksinussyndrome.

Acutecardiacinfarctwithcomplications(bradycardia,severehypotension,leftheartinsufficiency).

Atrialfibrillation/flutterandsimultaneouspresenceofaWPW(Wolff-Parkinson-White)syndrome(increased

riskoftriggeringaventriculartachycardia).

Manifestmyocardialinsufficiency.

Aswithanyothercalciumantagonist,diltiazemshouldnotbeadministeredconcurrentlywithdantrolene

infusionbecauseoftheriskofventricularfibrillation.

Hypersensitivitytodiltiazemoranyoftheexcipients.

4.4Specialwarningsandprecautionsforuse

Diltiazemshouldbeusedwithcautioninpatientswithreducedleftventricularfunction.Patientswithmild

bradycardia,firstdegreeAVblockorprolongedPRintervalshouldbeobservedclosely.

Theuseofdiltiazemindiabeticpatientsmayrequireadjustmentoftheirdiabeticmedication.

Theproductshouldbeusedwithcautioninpatientswithhepaticdysfunction.Abnormalitiesofliverfunctionmay

appearduringtherapy.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Diltiazemhydrochloridehasbeensafelyusedincombinationwithbeta-blockers,diuretics,ACEinhibitorsandother

anti-hypertensivedrugs.Patientsoncombinedtherapyshouldberegularlymonitored.However,becauseofthe

possiblesynergistichypotensiveeffectofdiltiazemandalpha-blockers,patientsreceivingthiscombinationshouldbe

strictlymonitored.

Althoughanaesthesiahasbeenperformedwithoutundueeffectonpatientsreceivingdiltiazem,theanaesthetistshould

beinformedthatthepatientisreceivingacalciumantagonist.

Aswithothercalciumantagonists,whendiltiazemisusedwithdrugswhichmayinducebradycardiaorwithother

antiarrhythmicdrugs,thepossibilityofanadditiveeffectshouldbeborneinmind.

Concurrentusewithdigitalis,carbamazepine,cyclosporinandtheophyllinemayleadtoincreasesintheirplasma

levels.

ConcurrentusewithcimetidineoranyotherH

antagonistmayincreaseserumlevelsofdiltiazemhydrochloride.

Usewithdiazepammaydecreaseserumlevelsofdiltiazemhydrochloride.

DiltiazemisknowntoinhibitCYP3A4andthereforemaycauseincreasedbloodconcentrationsofsubstratesofthis

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DiltiazemundergoesbiotransformationbycytochromeP-450mixedfunctionoxidase.Co-administrationwithother

agents,whichfollowthesamerouteofbiotransformationmayresultincompetitiveinhibitionofmetabolism.

Diltiazemhydrochloridewillnotprotectagainsteffectsofwithdrawalof-adrenoceptorblockingagentsnorthe

reboundeffectsseenwithvariousantihypertensives.Combinationwith-adrenoceptorblockershavingasignificant

“firstpass”losse.g.propranololmayrequireadecreaseintheirdoseandmayleadtobradycardia.

Thesimultaneousadministrationofdiltiazemwithdrugssuchas-blockers,antiarrythmicsorheartglycosidesmay

causeagreaterdegreeofAVblocking,reducetheheartrateorinduceahypotensiveeffect.Intravenousadministration

of-blockersshouldbediscontinuedduringtherapywithdiltiazem.

Therehavebeenreportsintheliteratureofdiltiazeminteractionswithwarfarin,rifampacinandlithium.

4.6Pregnancyandlactation

Studiesinanimalshaveshownteratogenicandembryotoxiceffects.Thedrugcrossestheplacentaandconcentratesin

foetaltissues.Intheabsenceofadequateevidenceofsafetyinhumanpregnancy,diltiazemshouldnotbeusedduring

pregnancyorinwomenofchildbearingpotential.

Diltiazemisalsoexcretedinbreastmilkandshouldnotbeusedinwomenbreastfeedinginfants.

4.7Effectsonabilitytodriveandusemachines

None.

4.8Undesirableeffects

Instudiescarriedouttodate,seriousadversereactionswithdiltiazemhavebeenrare;however,itshouldberecognised

thatpatientswithimpairedventricularfunctionandcardiacconductionabnormalitieshaveusuallybeenexcludedfrom

thesestudies.

In900patientswithhypertension,themostcommonadverseeventswereoedema(9%),headache(8%),dizziness

(6%),asthenia(5%),sinusbradycardia(3%),flushing(3%),andfirstdegreeAVblock(3%).Onlyoedemaandperhaps

bradycardiaweredoserelated.Themostcommonadverseevents(>1%)observedinclinicalstudiesofover2100

anginaandhypertensivepatientsreceivingdiltiazemwere:oedema(5.4%),headache(4.5%),dizziness(3.4%),

asthenia(2.8%),first-degreeAVblock(1.8%),flushing(1.7%),nausea(1.6%),bradycardia(1.5%),andrash(1.5%).

Lesscommonadverseeventshaveincludedthefollowing:

Cardiovascular:Angina,arrhythmia,AVblock(secondorthirddegree),congestiveheartfilure,hypotension,

palpitations,syncope.

Nervoussystem:Amnesia,depression,gaitabnormality,hallucinations,insomnia,nervousness,paraesthesia,

personalitychanges,somnolence,tinnitus,tremor.

Gastrointestinal:Anorexia,constipation,diarrhoea,dyspepsia,mildelevationsofalkalinephosphatase,SGOT,

SGPTandLDH(seeSpecialWarningsandPrecautions),vomiting,weightincrease,gingivalenlargement.

Dermatologic:Petechiae,pruritus,photosensitivity,urticaria,Allergicskinreactionsincludingerythema

multiforme,vasculitis,lymphadenopathyandeosinophiliahavebeenobservedinisolatedcases.Dermatological

eventsmaybetransientandmaydisappeardespitecontinueduseofdiltiazem.Shouldadermatologicreaction

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Other:Amblyopia,CKeleveation,dyspnoea,epistaxis,eyeirritation,hyperglycaemia,nasalcongestion,

nocturia,osteoarticularpain,polyuria,sexualdifficulties.

Skinandsubcutaneoustissuedisorders:Acutegeneralisedexanthemaspustules,hyperpigmentation.

4.9Overdose

Experienceofoverdosageinmanislimitedbutcasesofspontaneousrecoveryhavebeenreported.However,itis

recommendedthatpatientswithsuspectedoverdoseshouldbeplacedunderobservationinacoronarycareunitwith

facilitiesavailablefortreatmentofanypossiblehypotensionandconductiondisturbancesthatmayoccur.

Mostpatientssufferingfromoverdosageofdiltiazembecomehypotensivewithin8hoursofingestion.With

bradycardiaandfirsttothirddegreeatrioventricularblockalsodevelopingcardiacarrestmayensure.Hyperglycaemia

isalsoarecognisedcomplication.Theeliminationhalf-lifeofdiltiazemafteroverdosageisestimatedtobeabout5.5–

10.2hours.Ifapatientpresentsearlyafteroverdosage,gastriclavageshouldbeperformedandactivatedcharcoal

administeredtoreducediltiazemabsorption.

Hypotensionshouldbecorrectedwithplasmaexpanders,intravenouscalciumcluconateandionotropicagents

(dopamine,dobutamine,isoprenaline),symptomaticbradycardiaandhighgradeAVblockmayrespondtoatropine,

isoprenalineoroccasionallycardiacpacingwhichmaybeusefulifcardiacstandstilloccurs.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Diltiazemisacalciumchannelblockingagent.Itselectivelyreducescalciumentryintovascularsmoothmusclecells

andmyocardialcells.Thisdilatesthecoronaryarteriesincreasingthesupplyofoxygentotheheart.Itreduces

systemicvascularresistance,therebyreducingoxygendemand,andmoderatestheheartrate.Thesecombinedeffects

reducecardiacwork.

Whengiveneitheraloneorwithabeta-blockertopatientswithpreservedventricularfunctiononlyminimalnegative

inotropiceffectshavebeenobserved.

5.2Pharmacokineticproperties

Diltiazemiswellabsorbedandundergoesfirstpassmetabolisminthelivergivingrisetotwomajorcirculating

metabolites,desacetyldiltiazemandN-monodemethyldiltiazem.Themeanplasmahalf-lifeis5hours.Itisexcreted

mainlyinfaecesandtoalesserextentinurine.Only0.2to4%ofdiltiazemisfoundunchangedintheurine.

5.3Preclinicalsafetydata

Administrationtopregnantmiceandratshasbeenassociatedwithdecreasedfoetalweight,vertebralandskeletal

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Methylhydroxypropylcellulose

Povidone

Ethylcellulose

Macrogol

Hydrogenatedvegetableoil

Magnesiumstearate

Talc

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove25 °

6.5Natureandcontentsofcontainer

Highdensitypolypropylenetabletcontainerwithtamper-evidentpolyethylenecap–packsof100tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

Generics(UK)Limited

StationClose

PottersBar

HertfordshireEN61TL

England

8MARKETINGAUTHORISATIONNUMBER

PA0405/030/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18 th

December1990

Dateoflastrenewal:18 th

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10DATEOFREVISIONOFTHETEXT

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