FENTANYL-HAMELN

Main information

  • Trade name:
  • FENTANYL-HAMELN Solution for Injection 50 Microgr Microgram/ ML
  • Dosage:
  • 50 Microgr Microgram/ ML
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FENTANYL-HAMELN Solution for Injection 50 Microgr Microgram/ML
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0971/001/001
  • Authorization date:
  • 29-09-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fentanyl-Hameln 50 microgram/mlsolution forinjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1 mlsolution forinjection contains

Fentanylcitrate 0.0785 mg

Equivalentto Fentanyl0.050mg

Iampoulewith 2 mlsolution forinjection contains

Fentanylcitrate 0.157 mg

Equivalentto Fentanyl0.10mg

Iampoulewith 10mlsolution forinjection contains

Fentanylcitrate 0.785 mg

Equivalentto Fentanyl0.50mg

Forexcipients, see6.1.

3PHARMACEUTICALFORM

Solution forinfusion.

Theproductisaclear, colourlesssolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Fentanylisashortacting opioid used

forneuroleptanalgesiaand neuroleptanaesthesia

asan analgesiccomponentin generalanaesthesiawith intubation and ventilation ofthepatient

foranalgesictreatmentin theintensivecareunitin patientsunderthecondition ofassisted ventilation

4.2Posologyandmethodofadminstration

Thedoseoffentanylisadjusted individually according to age, body weight, physicalstatus, pathologicalcondition

and co-medication aswellastypeofsurgicalprocedureand typeofanaesthesia.

Forguidance, thefollowing dosageschedulesareproposed. Forother, specialdosagerecommendationsplease

referto theliterature.

Neuroleptanalgesiaand neuroleptanaesthesia

Forneuroleptanalgesiaadultsnormally willrequirean initialdoseof50 to 100 microgram(0.7-1.4 microgram/kg)

fentanylslowly injected intravenously in acombination with aneuroleptic(preferably Droperidol). Ifnecessary a

second dosageof50 to 100 microgram(0.7-1.4 microgram/kg)fentanylcan begiven 30 to 45 minutesafterthe

initialdose.

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200 to 600microgram(2.8-8.4 microgram/kg)fentanylslowly injected intravenously in combination with a

neuroleptic(preferably Droperidol). Thedosagedependson theduration and theseverity ofthesurgicalprocedure

and on themedication used forgeneralanaesthesia. Formaintenanceofanaesthesiaadditionaldosesof50 to 100

microgram(0.7-1.4 microgram/kg)fentanylcan begiven every 30 to 45 minutes. Thetimeintervalsand dosesof

theseadditionaladministrationshaveto beadjusted according tothecourseofthesurgicalprocedure.

Analgesiccomponentin generalanaesthesia

Adults:

Forinduction:Iffentanylisused asan analgesiccomponentin generalanaesthesiawith intubation and ventilation

ofthepatient, in adultsinitialfentanyldosesof70–600 microgram(1-8.4 microgram/kg)can beapplied as

adjunctto generalanaesthesia.

Formaintenanceofanalgesiaduring generalanaesthesiaadditionaldosesof25-100 microgram(0.35-1.4

microgram/kg)fentanylareto beinjected subsequently. Thetimeintervalsand thedosagearetobeadjusted

according to thecourseofthesurgicalprocedure.

Children:

In children of2 to 12 yearsofage, asingleanalgesicdoseof1-3 microgramfentanyl/kg body weightisused, for

examplein combination with inhalationalanaesthesia. Ifonly nitrousoxideisused in combination with fentanyl,

theinitialdoseisin therangeof5–10 microgramfentanyl/kg body weight.

Formaintenanceofanalgesiaduring generalanaesthesia, additionaldosesof1.25 microgram/kg fentanylmay be

given, dependingon thecourseoftheoperation.

Pain managementin theintensivecareunit

Forusein pain managementofventilated patientsin theintensivecareunitthedosageoffentanylhasto be

adjusted individually, depending on thecourseofpain and onconcomitantmedication. Normally theinitialdoses

arein therangeof50 to 100 microgrami.v. (0.7-1.4 microgram/kg), butcan betitrated higherifnecessary. The

initialdosenormally isfollowed by repeated injections, oftotally up to 25 to 125 microgramfentanylperhour

(0.35-1.8 microgram/kg/h).

Dosagein elderly and weak patients

Theinitialdosein elderly and weak patientsshould bereduced. Theeffectoftheinitialdoseshould betaken into

accountforthedetermination ofsupplementaldoses.

Dosagein patientswith chronicopioid medication

In patientswith chronicopioid medication orwith aknown history ofopioid abuseahigherdosageoffentanyl

may benecessary.

Dosagein patientswith additionaldiseases

In patientswith oneofthefollowing diseasestheintended dosageoffentanylshould betitrated very carefully:

uncompensated hypothyreosis

lung diseases, especially thosewith reduced vitalcapacity

alcoholabuse

impaired hepaticfunction

impaired renalfunction

Caution isalso required iffentanylisto beadministered to patientswith adrenalinsufficiency, prostatic

hypertrophy, porphyriaand bradyarrhythmia.

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to beeitherreduced orincreased.

In thesepatientsaprolongedpostoperativemonitoring period isrecommended.

Method and durationofadministration

Fentanylshould beadministered slowly (1-2 minutes)by intravenousinjection (seealso“Specialwarningsand

precautionsforuse”),ifapplicablein combinationwith aneuroleptic(preferably Droperidol).

In anaesthesiatheduration ofadministration dependson thetimecourseofthesurgicalprocedure. In pain

managementofintensivecarepatientsthephysician hasto determinetheduration ofadministration according to

theintensity and thetimecourseofpain.

4.3Contraindications

Fentanylshould notbeused in patientwith:

Known hypersensitivity to fentanyl, othermorphinomimeticsorto any oftheexcipients.

Respiratory depression withoutartificialventilation.

Aco-medication ofMAOinhibitorsorwithin two weeksaftercessation ofadministration

ofMAOinhibitors.

Increased intracranialpressureand brain trauma

Hypovolaemiaand hypotension

Myastheniagravis

4.4Special warningsandspecialprecautionsforuse

Intravenousfentanylshould only beused by atrained anaesthetistin hospitalsorotherlocationswith facilitiesfor

intubation and assisted ventilation.

Thevitalfunctionsofthepatienthaveto bemonitored routinely. Thisalso appliesto thepostoperativeperiod.

Fentanylhasastrong dose-dependentdepressing effecton respiration which may beprolonged especially in the

elderly. In neonates,respiratory depression isto beexpected already aftersmalldoses. Generally, therisk ofa

delayedrespiratory depression hasto beconsidered. In casesofemergency appropriateinstrumentsandmedicinal

producthaveto beavailable.

In isolated cases, in epilepticpatientsafterarapid and high dosagefentanylapplication (19-36 microgram/kg)of2

to 5 minutesduration,an electricalseizureactivity wasrecorded electrocorticographically even in healthy brain

regions. An impacton theintraoperativeelectrocorticographicfocuslocalisation afterlowerfentanyldosesisnot

known untilnow.

Musclerigiditymay occurwhich may also lead to respiratory depression. Theincidenceofthisrigidity maybe

decreased by slowintravenousadministration. Thereaction can betreated by controlled ventilation and when

necessary by administration ofamusclerelaxant.

Non-epileptic(myo)clonicreactionsmay occur.

Afterfentanylan increaseofthebileductpressureand in isolated casesaspasmoftheSphincterofOddican be

observed:Thishasto betaken into accountduring intraoperativediagnosticprocedurein bileductsurgery and in

pain managementofintensivecarepatients.

Asallotheropioids, fentanylcan havean inhibitory effecton intestinalmotility. Thisshould beconsidered in the

pain managementofintensivecarepatientswith inflammatory orobstructiveintestinaldiseases.

Bradycardiaand asystoliamay occurwhen thepatienthasreceived an insufficientdoseofan antimuscarinicagent

orwhen fentanyliscombined with non-vagolyticmuscle-relaxants. Bradycardiaistreated with atropine.

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failure. Induction dosesshould beadapted and administered slowly, in orderto preventcardiovasculardepression.

Appropriatemeasuresshould betaken to maintain astablearterialpressure.

In neonates, thereisasufficientlikelihood ofdeveloping awithdrawalsyndromeaftertreatmentofmorethan 5

daysoratotaldoseof>1.6mg/kg.

Theuseoffastbolusinjectionsoffentanylshould beavoided.

Patientswith hepaticfailureshould bedosedcarefully becauseoftheprobably disturbed metabolism.

Patientswith renalinsufficiency should becarefully checked on thesymptomsoffentanyltoxicity. Asaresultof

dialysisthevolumeofdistribution offentanylmay bealtered, which can influencetheserumconcentrations.

When fentanylisgiven togetherwith droperidol, theusershould befamiliarwith thespecificpropertiesand

undesirableeffectsofboth medications.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Agentslikebarbiturates, benzodiazepines, neuroleptics, volatileanaestheticscontaining halogensorother

medicamentsthathaveanon-selectivedepressanteffecton thecentralnervoussystem(i.e. alcohol), may augment

therespiratory depression caused by opioids. When such medicamentshavebeen administered to patients, the

required doseoffentanylwillbelowerthan usual. Thisshould also resultin lowering thedoseofother

medicamentswhich haveadepressanteffecton thecentralnervoussystem,when theseagentsareadministered

afterfentanylisgiven.

With higherdosesoffentanyltheconcomitantapplication ofnitrousoxideoreven smalldosesofdiazepamcan

lead to an impairmentofcardiovascularfunction.

Thecombined application offentanyland midazolamcan lead to adecreasein blood pressure.

Simultaneousapplication ofdroperidolcan lead to afallin blood pressure, butin somecasesalso arisein blood

pressurewasobserved. Thepulmonary arterialpressurecanbedecreased. Furthermore, shivering, restlessnessand

postoperativeepisodesofhallucinationsmay occur.

In patientswith preceding medication with MAOinhibitorswithin thelast14 daysbeforeopioid administration

life-threatening interactionswith pethidineon thecentralnervoussystem(i.e. agitation, musclerigidity,

hyperpyrexia, convulsions), and therespiratory and circulatory system(i.e. circulatory depression, hypotension,

haemodynamicinstability and coma)havebeen observed and cannotberuled outwithfentanyl.

MAO-inhibitorsalso block theenzymeswhich metabolisecentrally activesubstances(sedatives, antihistamines,

opioids, etc.). Asaconsequencean intensiveand prolonged effectoffentanylmay occur, including respiratory

depression.

Apreceding administration ofcimetidinemay lead to increased plasmalevelsoffentanyl.

Co-administration ofclonidinemay enhancefentanyleffectsand especially prolong fentanyl-induced ventilatory

depression.

Vecuroniumcan causehaemodynamicdepression when combined with fentanyl. Significantdecreasesin heart

rate, mean arterialpressure, and cardiacoutputmay occurwhich arenotdependenton thedoseofvecuronium.

Bradycardiamay develop during thecombined application ofatracuriumand fentanyl.

Fentanyleffectsareenhanced and prolonged when combined with baclofen.

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metabolismoffentanylby theliverso thatfentanyliscleared fromthebody morequickly. Amarked increasein

thefentanylrequirementsshould beanticipated in any patienton long-termtreatmentwith theseanticonvulsants,

butnotwith sodiumvalproate.

4.6Pregnancyandlactation

Thereareno sufficientclinicaldataavailableto evaluatepossiblerisksoftheuseoffentanylduring pregnancy. Forthis

reason fentanylshould notbeused in thisperiod.

Itisadvised notto usefentanylduring delivery, becausefentanylpassestheplacentaand maycauserespiratory

depression in theneonate. In obstetrics, fentanylmay only beused intravenously afterclamping theumbilicalcord. The

placentaltransfer(fetal:maternalratio)amountsto 0.44 (1.00:2.27).

Fentanylpassesinto breastmilk. Aftertheapplication offentanylbreastfeedingshould bestopped foratleast24

hours.

4.7Effectsonabilitytodriveandusemachines

Theuseoffentanylmay causeadecreased levelofreactivenessand concentration.

Patientsshould beadvised thattheperformanceofskilled taskssuch asdriving oroperatingmachinery may be

impaired foraconsiderabletimeafteradministration offentanyl.

Patientsshould beaccompanied on theirway homeafterdischargeand should beinstructed to avoid alcohol.

4.8Undesirableeffects

Very common: >1/10

Common: >1/100 and <1/10

Uncommon: >1/1000 and <1/100

Rare: >1/10 000 and <1/1000

Very rare: <1/10 000 including isolated cases

Blood and lymphaticsystemdisorders

Rare: Methaemoglobinemia

Immunesystemdisorders

Rare: Anaphylaxis

Psychiatricdisorders

Very rare: Administration offentanyloveralongerperiod oftimemay causethedevelopment

oftolerance. Thedevelopmentofdrug dependencecannotberuled out.

Nervoussystemdisorders

Very common: Sedation

Common: Vertigo, euphoria, nausea, vomiting

Rare: Cerebralseizures. Afterinfusionsoffentanyloflong duration in children movement

disturbances, increased sensitiveness.

Eyedisorders

Rare: Miosis, visiondisturbances

Cardiacdisorders

Common: Bradycardia

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Vasculardisorders

Common: Hypotension, especially in hypovolaemicpatients

Rare: Orthostaticregulatory disturbances

Respiratory, thoracicand mediastinaldisorders

Very common: Respiratory depression

Depending on dosagefentanylcausesrespiratory depression up to apnoealasting normally only afewminutesat

lowdoses, butmany hoursathigh doses. Therespiratory depressanteffectmay lastlongerthan theanalgesiceffect

and may re-occurin thepostoperativeperiod. Postoperativemonitoring isthereforecompulsory.

Common: Thoracicstiffness, possibly resulting in impaired ventilation

Rare: Laryngospasm

Very rare: Pulmonary oedema,bronchospasm

Gastrointestinaldisorders

Rare: Constipation, singultus

Hepato-biliary disorders

Rare: SpasmofthesphincterofOddi.

Skin and subcutaneoustissuedisorders

Rare: Pruritus, urticaria

Musculoskeletal, connectivetissueand bonedisorders

Common: Musclerigidity,myoclonicmovements

Renaland urinary systemdisorders

Rare: Increased muscletoneoftheureter, urinary retention especially in patientswith

prostatichypertrophy.

Generaldisordersand administration siteconditions

Rare: Opioid withdrawalsymptoms, sweating.

4.9Overdose

Symptoms

Overdosageoffentanylexpressesitselfby prolongation oftheduration ofthepharmacologicaleffects. Dependent

on theindividualsensitiveness, theclinicalpictureisrespiratory depression rangingfrombradypnoeato apnoea,

bradycardiaup to asystole, decreasein blood pressure, circulatory failure, coma, seizure-likeactivity, muscle

rigidity ofthechestwall, trunkand extremities, and pulmonary oedema.

Treatmentofoverdose

Hypoventilation should betreated by administration ofoxygen and thepatientshould beventilated. Respiratory

depression should betreated by administration ofan opioid antagonistlikenaloxone. Theusualinitialnaloxone

doseamounts0.4 to 2mg. Ifno effectcan beseen, thisdosemay berepeated every 2 to 3 minutesup to reversalof

respiratory depression orawakening. Sincetherespiratory depressanteffectoffentanylmay lastlongerthan the

antagonisticeffect, repeated dosesofnaloxonemay beappropriate.

Ventilatory problemscaused bymusclerigidity can bediminished orabolished by application ofaperipherally

acting musclerelaxant. Thepatientshould bemonitored carefully. Normalbody temperatureand balanced fluid

volumesshould beensured. In thecaseofsevereand persistenthypotension, hypovolaemiashould beconsidered,

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Opioid analgesics

ATC-code:N01AH01

Fentanylisapotentopioid analgesicwhich may beused asan analgesicsupplementwith generalanaesthesiaoras

an anaestheticagentalone.

Fentanylpossessesµ-agonisticproperties. Theagonisticbehaviourto-and-receptorsiscomparableto

morphine. Adoseof100 microgram(2ml)hasan analgesicaction which iscomparablewith 10 mg morphine.

Fentanylhasarapid onsetofaction. Themaximumanalgesiceffectand thedepressantaction on therespiration

takeplacewithin afewminutes.

Theaverageduration ofaction oftheanalgesiceffectisabout30 minutesafterasinglebolusinjection of100

microgram. Thelevelofanalgesiaisdoserelated and may beadjusted to thepain levelofthesurgicalprocedure.

Fentanylexhibitsrelatively smallcardio -circulatory effectsbuthasastrong depressiveeffecton respiration. Stress

induced hormonalchangesarenotreliably suppressed by fentanyl. An increasein blood pressuredueto

intraoperativepain stimulimay occurin spiteofhigh dosefentanyltreatment.

Depending on dosageand rateofinjection fentanylmay causemusclerigidity, euphoria, miosisand bradycardia.

Intradermaltestsand serumdeterminationsofhistaminein humans, aswellasin-vivo testsin dogs, showed that

clinically significanthistaminereleaseafterfentanylapplication israrely observed.

Alleffectsoffentanylcan beantagonised by specificopioid-antagonistslikenaloxone.

5.2Pharmacokineticproperties

Afterintravenousinjection thefentanylplasmaconcentrationsdecreaserapidly. Thedisposition offentanylis

triphasicwith half-lifesofabout1 minute, 15 minutesand 6 hours. Fentanylhasavolumeofdistribution ofthe

centralcompartmentofabout15 litresand atotalvolumeofdistribution ofabout400 litres.

Especially in elderly patientsorafterrepeated administration, half-lifesmay beprolonged. Secondary peak plasma

levelsmay occur.

Fentanylisbound to plasmaproteinsfor80–85%.

Fentanylismetabolised rapidly, mainly in theliver, mainly by oxidativeN-desalkylation. Theclearanceisabout

0.5 1/hour/kg. About75%oftheadministered doseiseliminated within 24 hours. Only 10%ofthedoseis

excreted asintactsubstance.

5.3Preclinical safetydata

Similareffectsaspreviously described forotheropioidswereobservedin repeated dosetoxicity studiesup to 4

weeks.

Animalstudieshaverevealed areduced fertility in femaleratsaswellasembryomortality, although no signsof

teratogenicity haveoccurred.

Mutagenicity studiesin bacteriaand rodentsrevealed no mutagenicpotentialoffentanyl. Aswellasotheropioids

fentanylshowed mutageniceffectsin vitro inmammalian cells. Theseeffectswereinduced only in very high

concentrations. Thereforefentanylisnotconsidered to poseagenotoxichazard to patients.

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumchloride

Waterforinjection

Hydrochloricacid orsodiumhydroxideforpHadjustment

6.2Incompatibilities

Thismedicinalproductmustnotbediluted with othersolutionsforparenteralusethan thosementioned in section

6.6 Instructionsforuseand handling.

Compatibility mustbechecked beforeadministration, ifintended to bemixed with otherdrugs.

Fentanylcitrateisreportedly physically incompatiblewith pentobarbitalsodium, methohexitalsodium, thiopental

sodiumand nafcillin.

6.3ShelfLife

Shelf-lifebeforefirstopening:

3 years.

Shelf-lifeafterfirstopening and/ordilution:

Fromthemicrobiologicalpointofview, thesolutionsordilutionsshould beused immediately. Ifnotused

immediately, in-usestoragetimesand conditionspriorto usearetheresponsibility oftheuserand would normally

notbelongerthan 24 hoursat2 to 8°C, unlessdilution hastaken placein controlled and validated aseptic

conditions.

6.4Special precautionsforstorage

Keepcontainerin theoutercarton in orderto protectfromlight.

6.5Natureandcontentsofcontainer

5 (10)ampoulesmadeofcolourlessglass, typeI, containing 2 or10mlsolution.

6.6Instructionsforuseandhandling

Usefingerprotection when opening an ampoule.

Theinjection isforsinglepatientuseand should beused immediately afteropening. Theinjection should notbeused if

particlesarepresent. Any unused portion should bediscarded.

Theproductcan beused eitherundiluted ordiluted. Dilution rangestested with 0.9%sodiumchlorideand 5%glucose

solutionsare1:1 and 1:25. Hencethemaximaldilution mustnotexceed 1 partfentanylwith 25 parts0.9%sodium

chlorideor5%glucosesolutions.

7MARKETINGAUTHORISATIONHOLDER

Hameln PharmaceuticalsGmbH

LangesFeld 13,

D-31789 Hameln

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8MARKETINGAUTHORISATIONNUMBER

PA971/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 29th September2000

Dateoflastrenewal: 16th February 2004

10DATEOFREVISIONOFTHETEXT

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