HISMANAL®
not recommended. lnfonnationforPatien~:
(astemizole)Table~
~i~~ ~:~i~~~g ~~~s~ri~~~~~:~plete prescribing information of INDICATIONS AND USAGE HISMANAL tablets are indicated for the relief of symptoms assoc~ted with seasonal allergic rhinitis and chronic idiopathic urticaria. HISMANAL should not be used as apr nproduct for immediate relief :~;:1\~~~:~t~t~~eh:~~~t:/~Ji~~d not to increase the dose in an Clinical~udieshavenotbeenconductedtoevaluatetheeffectivenessof
Paten~ taking HISMANAt.' (astem~ole) shou~ receWe the follol'ing infonnaton and instructions. Anth~mrnes are prescribed to reduce al~rgic symptoms. Patien~ takrng HISMANAt. should be a(Msed t) to adheretotherecommendeddose,and2)thattheuseofexcessWedoses · Some patients appear to toaccelerntetheonsetof TO DO THIS and not to use HISMANAL asap r nproduct for immediate relief of symptoms. Patien~shouldbequestionedabou1useofanyotherprescriptionor
over-the-counter medication, and should becau1ioned regardin the
HISMANAL in the common cold. I actation used in
otent~l
risk tot usorbahy. (SeePrmnanc~subsection.) lnadd~ionhpatients
=~ ~~u~siWe~:d~~ta~~ ad~~~J~~ ~~o~rt~ ::for ii1ea~
thourafterdosing.PatentsshouldalsobeinstructedtostorethislliW· icationinatiihftlclosedcontainerinacool,dryplace,awwtfromheat ordirectsunrghl,andawayfromchildren. Ca~inogenesis,Mutagenesis lmpainnentoffertility: Ca~ino~enicpotentialhasnot~eenrevealedinrntsgWen260xtherec·
l~e~e~e~~~~e~~~ 0iua~;~~~~ 16r lam~~~~sor~1c~~c1:~ 1 2
dominant lethal, sister chromatid exchange and Ames tests of astemf zolehavenotrevealedmutagenicactivity, lmpainnent of fertility was not obseNed in male or female rn~ gWen 200X the recommended human dose. Pregnancy:PregnancyCatego~C:
Teratogemc effects were not obseNed in rats administered 200X the recommended human dose or in rnbbits given 200X the recommended human dose. Maternal toxicity was seen in rnbbits administered 200X the recommended human dose. Embryocidal effects accompanied by maternal toxicity were obseNed at tOOX the recommended human dose in rnts. Embryoloxici or maternal toxicity was not obseNed in rnts or shouldbeusedduring thepotentialrisktothefetus.Metaboresmayremainintheb toras longas4monthsaftertheendofdosing,calculatedonthebasisof6 timesthetenninalhaH-Iile. Nu~iniMothe~:
It is no knownwhetherthisdrug isexcretedinhumanmilk.llecause
certaindrugsareknowntobeexcretedinhumanmil~cau1ionshould be exe~islid when HISMANAL is administered to anu~ing woman.
HISMANAL is excreted in the mrlk of dogs. Pediatric Use: Safety and efficacy in children under12yea~ofagehasnotbeen demonstrnted. ADV.ERSE REACTIONS events {e.g. card~c INDIC~TJONS and rh~hmiashas
~eentln=e~~;~ti~~~~ ~bw:ora~s~~~~n~~~o~~~~ ~~ANAL use, which may reftect undetected ventricular arrhythmia.
Thereportedincidencesofadve~ereactionslistedinthefollowingtable
arederivedfromcontrolledclinicalstudiesinaduHs.lnthesestudresthe usual maintenance dose of HISMANAL was 10 mg once dai~.
ADVERSE EVENT Central Nervous System Drowsiness Headache Fatigue
PercentofPatientsRe ortln ConiJolledStudles' HISMANAL PLACEBO CLASSICAL" {No16JOI {N•1109) (N-.J04) % % %
&~m~~~~~~~ NeM!usness
Oizzt GastromtestinaiSystem Nausea Diarrhea Abdominal pain Eye,Ear,Nose, and Throat Moulhdry Pharyngi!IS Conjunctrvttis Olher Arthrnlgia
7.t 6.7 4.2 3.9 3.6 2.1 2.0
6.4 9.2 1.6 1.4 0.7 1.2 1.8
22.0 3.3 11.8 0.0 1.0 0.3 1.0
2.5 1.8 1.4
2.9 2.0 1.2
1.3 0.7 0.7
5.2 1.7 1.2
3.8 2.3 1.2
7.9 0.3 0.7
1.2
1.6
0.0
DuratronoftreatmentrnControlledStudresrnngedfrom7to182Days "Classical Drugs: Clemastine (N·137); Chlo~henirnmine (N·tOO); Phenirnmine Maleate (N>l7);d-Ghlo~henirnmine (N·20) are taking medications WhiCh are reported o prolong QT inteNals
~:.d~~~o:~~~~t~:~~~n~~t~~~~m~~~~~~1e~ti~~~~e~
bepndil, and tertenadine), patien~ with electrolyteabnonnal~ies such as hypokalemia or hypomagnesemia, or those taking diuretics w~h potential for inducing electro\•teabnonnal~ies. Rare cases of cardiovascular even~ have been obseNed inpatien~ w~h hepaticdvsfunction. Systematic evaluation of the phannacokinetics of asfemizore in patien~ w~h hepatic dysfunction has not been jlilrtonned. Since astemizole is e~ensive~ metabolized hy the IWer, the use of HISMANAL in patien~ with significant hepatic dysfunction should ge~ ernl~beavoided.
PRECAUTIONS Geneml: Cau1ion should be given to potential anticholine~ic (drying effects) in
1;~~i~~ ~~~1dw~ea ~:a di~e~\fents with cinhosis or other liver diseases. HISMANAL does not appear to be dia~ble. Caulon should also be used when treating patients with renal rmparrment. Druglntemctions: See CONTRAINOICATIONS and WARNINGS mons for discussion of infonnation regarding potential drug internctions. Ketoconazole,lfmconazole Concomitant admini~tion of kefoconazole table~ or ~conazole M~~~eG~i~J~.i s contmindicated. (See CONTRAINDICATIONS and
angroedema, asymptomatic IWer enzyme elevations, bronchospasm: depression, edema, epistaxs, hepat~is, myalgia, palp~on, paresttresia, photosens~Wity. pruntus, and rnsh.
Ma~etingexpenencesincludeiso~tedcasesofconvulsions.Acausal
relationship with HISMANAL has not been established. OVERDOSAGE lntheeventofoverdosage lavage and emesis should HISMANAL can cause death,
1
1
Due to the chemical simrlarity of fluconazole, metronidazole, and miconazolei.v.toketoconazole,concomrtantuseoftheseproductswitl astemizoleisnotrecommended.
ISTRA ION. ~~~~nw~i:rd~;~:~been reported witl overdose and may be Overdose patients should be careful~ mon~ored as long as the QT inter-
valisprolongedorarrh~hmiasarepresent.lnsomecases,thishas beenuptosixdijs.lnoverdosecasesinwhichventriculararrh~hmias are associated w~h significant QTfrolongation, treatment with antiar-
rhvthmics known to prolong Q inteNals rs not recommended. HISMANAL does not a ear to be dia ble. 2052m!Vkginmiceand3154 neonatal rnts, the ornl LD50 was 905 m!Vkg in males in females. Re~sedMa~h1993,Ju~1993
a~emizoleiscon
WARNINGS BOX.) Concomitant a ministrntion of astemizole w~h other macrolrde antibiotics, includingtroleandomycin, az~hromycin, andclarithromycin, is
JANSSEN
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