Mcc 34 Domperidone

7/24/2019 Mcc 34 Domperidone

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DOMPERIDONE (MOTILIUM) TABLETS

At the 33rdmeeting on 9 June 2005, the Medicines Classification Committee considered

an application to reclassify domperidone from prescription medicine to restricted

medicine for the symptomatic relief of nausea and vomiting and for the treatment ofsymptoms of dysmotility-lie dyspepsia!

"he Committee concluded that the application as it stood #as not accepta$le for sale ofdomperidone as a restricted medicine and recommended that there $e no change to the

current prescription medicine classification! "he Committee did, ho#ever, note the

follo#ing%

&'n order to $e accepta$le for reconsideration, the Committee #as of the opinion

that the su$mission should% acno#ledge that medication is not $est practice for

vomiting and not include this as an indication limit pac si(es to 20 ta$lets for

limited duration and #ith a ma)imum daily dose of *0 milligrams contain draftla$elling appropriate for +"C sale!

Janssen-Cilag ty .td accepts these comments and #ould lie the Committee to consider

this revised application for reclassification of domperidone!

"he application consists of the follo#ing documents%

/! evised art A 1eneral 'nformation

2! Copy of the relevant minute from the 33rdMCC meeting

3! 4raft la$elling te)t for +"C M+"'.'M

*! +verseas e)ample of pacaging for +"C M+"'.'M 1e)! 'reland

5! roposed Consumer Medicine 'nformation for +"C M+"'.'M

6! Copy of the current approved M+"'.'M 4ata 7heet

8! Copy of the original application1As discussed #ith the MCC 7ecretary, rather than re-su$mitting the full documentation

supplied in January 2005, only pages /-35 of the original application have $een provided!

Copies of the /6 attachments to the original application are availa$le on reuest

Please note that in this application for OT !se of MOTILIUM"

The #o$itin% in&ication has 'een re$o#e&

The pac si*e has 'een li$ite& to +, ta'lets

The &!ration of treat$ent has 'een li$ite& to -. ho!rs

4omperidone 1M+"'.'M: ta$lets ; application for reclassification January 2005

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The $a/i$!$ &ail0 &ose has 'een li$ite& to -, $%


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PART A 1 2ENERAL IN3ORMATION

International Non4proprietar0 Na$e"

4omperidone

Proprietar0 na$e"M+"'.'M:

Na$e of co$pan05or%anisation re6!estin% reclassification"

Janssen-Cilag ty .td

Dose for$ an& stren%th for 7hich a chan%e is so!%ht"

"a$lets, /0 mg

Pac si*e an& other 6!alifications"

Ma)imum +"C pac si(e limited to 20 ta$lets 4uration of +"C treatment limited to *< hours

Ma)imum +"C daily dose limited to *0 mg

In&ications for 7hich chan%e is so!%ht"

7ymptomatic treatment of nausea

"reatment of the symptoms of dysmotility-lie dyspepsia% sense of fullness,

feeling of a$dominal distension, eructation, flatulence and heart$urn

Present classification of $e&icine"

rescription Medicine

lassification so!%ht"

estricted 1harmacist +nly Medicine

lassification stat!s in other co!ntries"

Australia% prescription medicine

=% over the counter 1+"C

7A% not mareted

Canada% prescription medicine

>elgium% +"C

'reland% +"C 'taly% +"C

Japan% +"C

?etherlands% +"C

7outh Africa% +"C

7#it(erland% +"C


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+ther countries #here domperidone is availa$le +"C include% China, ussia,

7lovaia, Malta, 7outh =orea, and omania


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E/tent of !sa%e in N8 an& else7here"

"he unit sales volumes for M+"'.'M in ?e# @ealand and Australia over the past 5

years are provided in the follo#ing ta$le%

[NB table containing commercially sensitive sales data withheld from the

document placed on the Medsafe website, under the provisions of section 9(2)(b)of the fficial !nformation "ct #9$2%

Dates of ori%inal consent to &istri'!te"

Consent to distri$ute M+"'.'M in ?e# @ealand #as given on 2< June /9

A copy of the proposed la$elling and the proposed CM' for +"C M+"'.'M is

provided!

Propose& 7arnin% state$ents""he relevant #arning statements are contained in the proposed CM' for +"C

M+"'.'M!

Other pro&!cts containin% the sa$e acti#e in%re&ient 7hich 7o!l& 'e affecte& '0

the propose& chan%e"

?one!


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RE9IE:ER;S 2UIDE

"his application sees the reclassification of domperidone /0 mg ta$lets from a

rescription Medicine to a estricted 1harmacist +nly Medicine #hen indicated for the

symptomatic treatment of nausea and vomiting and for the treatment of symptoms ofdysmotility-lie dyspepsia!

"he information contained in this application falls into three categories%

eneral information 1art A

'nformation #hich is specifically related to nausea and vomiting 1art >/!

'nformation #hich is specifically related to dyspepsia 1art >2!

eneral information #hich is related to the medicine, irrespective of indication

1art >3!

"o avoid repetition and overlapping of the a$ove categories, the structure of the

application is as follo#s%

)ecutive 7ummary

esponse to the report prepared $y Medsafe for

consideration $y the MCC in March /999

art A eneral information

art >/ ; ?ausea and vomiting 'nformation specifically related to nausea and

vomiting

art >2 ; 4yspepsia

'nformation specifically related to dyspepsia

art >3 ; eneral eneral information, irrespective of indication

Conclusions

Attachments / ; /6


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E


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.ie#ise, the general pu$lic is e)perienced in using +"C medicines to treat dyspepsia!

Eor many years advertising and consumer education campaigns have highlighted the

symptoms of dyspepsia to consumers, and it is no# #ell accepted as a pro$lem that iseasily and safely treated #ith +"C medications!

4omperidone ta$lets have an e)cellent safety profile! Medsafe considers in its March/999 report that domperidone is safer than metoclopramide and #e also $elieve it is safer

than prochlorpera(ine! 4omperidone is also #ell tolerated! "his is illustrated $y the very

lo# incidence of adverse reactions reported locally and internationally during the use ofdomperidone since the first international registration in >elgium in March /98

4omperidone has $een mareted in ?e# @ealand and internationally for over 20 years!

4uring this time the safety and adverse reaction profile of the medicine has $een clearlydefined! "he e)tensive no#ledge gained a$out the product, #hich far e)ceeds the

minimum standards for +"C consideration, means it is e)tremely unliely that the

medicine #ould $ehave in an unpredicta$le manner once reclassified to a estricted

1harmacist +nly Medicine!

Einally, the general pu$lic has a right of access to an effective and safe treatment fornausea and vomiting and dyspepsia that usually does not cause dro#siness or

e)trapyramidal symptoms, #hich are adverse reactions reported for some of the other

currently availa$le +"C treatments!


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RESPONSE TO T>E REPORT PREPARED B= MEDSA3E

3OR ONSIDERATION B= T>E M IN MAR> ?@@@

De are concerned #ith some of the statements made in the Medsafe report! 7ome adverse

reactions to domperidone #hich are considered to $e relatively rare seem to tae undueprominence in the report! De therefore #ish to tae this opportunity to highlight

particular e)amples and give our interpretation of their freuency, severity and hence

relative importance!

De have revie#ed the reports received $y the Centre for Adverse eactions Monitoring

1CAM in ?e# @ealand and the "herapeutic oods Administration 1"A in Australia!

As at 30 June 2003, CAM had only received /* reports involving domperidone!'nformation on /3 of these reports is provided in the CAM printout dated 30 7eptem$er

/999 1see Attachment 3 H?> an updated listing has $een reuested from CAM and #ill

$e provided #hen this $ecomes availa$leI! 'n the printout of reports received up to /0

January 2005, "A had only received 22 reports involving domperidone 1see Attachment5!

De have also revie#ed the reports received $y the company from around the #orld! "he

latest eriodic 7afety pdate eport 17 for domperidone 1see Attachment 6 covers

the period from 2 January 2003 to / January 200*, and covers an estimated e)posure todomperidone in this revie# period of appro)imately


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involves epilepsy or sei(ures! "he 7 records si) cases of convulsion out of the

estimated


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"he Medsafe report also comments that &domperidone can 1$ut does not readily cross

the $lood- $rain $arrier and therefore can cause adverse central effects! "here have $een

reports of dystonic reactions! 't is important to reiterate that due to its uniue structure,domperidone has very limited penetration of the $lood $rain $arrier! "he

central%peripheral ratio for domperidone is appro)imately /%300, compared #ith /%*5 for

metoclopramide! "his in practice means a very lo# incidence of central effects!

Einally, the Medsafe report comments that &heart$urn is $etter treated #ith antacids or B 2antagonists #hich are also availa$le +"C! 't has $een esta$lished that B 2antagonists arenot effective in the treatment of dysmotility-lie dyspepsia and that antacids are not

effective in the treatment of either acid related or dysmotility-lie dyspepsia 1see later!

4omperidone has demonstrated efficacy in the treatment of heart$urn caused $y motility

pro$lems! "hat is, B2 antagonists should $e used for acid related heart$urn $utdomperidone is more appropriate for heart$urn caused $y motility pro$lems!


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PART A 1 2ENERAL IN3ORMATION

International Non4proprietar0 Na$e"

4omperidone

Proprietar0 na$e"M+"'.'M:

Na$e of co$pan05or%anisation re6!estin% reclassification"

Janssen-Cilag ty .td

Dose for$ an& stren%th for 7hich a chan%e is so!%ht"

"a$lets, /0 mg

Pac si*e an& other 6!alifications"

ac si(e of /0 or 20 ta$lets

In&ications for 7hich chan%e is so!%ht"

7ymptomatic treatment of nausea and vomiting

"reatment of the symptoms of dysmotility-lie dyspepsia% sense of fullness,

feeling of a$dominal distension, eructation, flatulence and heart$urn

Present classification of $e&icine"

rescription Medicine

lassification so!%ht"

estricted 1harmacist +nly Medicine

lassification stat!s in other co!ntries"

Australia% prescription medicine

=% over the counter 1+"C

7A% not mareted

Canada% prescription medicine

>elgium% +"C

'reland% +"C

'taly% +"C

Japan% +"C ?etherlands% +"C

7outh Africa% +"C

7#it(erland% +"C

+ther countries #here domperidone is availa$le +"C include% China, ussia,

7lovaia, Malta, 7outh =orea, and omania!


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?ote that the international regulatory status of M+"'.'M is provided as Appendi) / of

the 7 document in Attachment 6!

E/tent of !sa%e in N8 an& else7here"

"he unit sales volumes for M+"'.'M in ?e# @ealand and Australia over the past 5

years are provided in the follo#ing ta$le%

[table containing confidential sales data withheld%

Dates of ori%inal consent to &istri'!te"

Consent to distri$ute M+"'.'M in ?e# @ealand #as given on 2< June /9

Eor information, a copy of the current 1i!e! &rescription Medicine la$elling for

M+"'.'M is provided in Attachment 8! "he &+"C la$elling for M+"'.'M #ould

reflect the information in the proposed CM' document provided in Attachment

Propose& 7arnin% state$ents"

"he relevant #arning statements are contained in the proposed CM' document for +"C

M+"'.'M 1see Attachment


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PART B? 1 NAUSEA AND 9OMITIN2

BENE3ITS TO BOT> T>E ONSUMER AND TO T>E PUBLI EE

PROPOSED>AN2E

4omperidone has an e)cellent safety profile and is #ell tolerated, maing it an

appropriate medicine to $e reclassified to a estricted 1harmacist +nly Medicine!

eclassification of domperidone #ould provide appropriate and easier access to a safetreatment option for a common symptom comple)! As a conseuence, patients could have

immediate access to a convenient and effective treatment for their condition!

'n general, nausea and vomiting can $e considered symptoms of conditions that are eitheracute, uncomplicated and self-limiting in nature, or symptoms of a serious underlying

condition!

"his application sees to allo# treatment of acute uncomplicated nausea and vomiting#ith +"C domperidone! At present, a patient #anting relief from acute nausea and

vomiting #ithout any o$vious underlying conditions must present to a ! "his places anunnecessary $urden on the health care system at a time #hen $udgets are strained!

Allo#ing the general pu$lic #ith the help of a harmacist to self-treat simple cases of

acute nausea and vomiting #ith a safe and effective medicine such as domperidone #illreduce the num$er of medical consultations and hence reduce demands on the healthcare

system!

7ome patients are unliely to consult a doctor for simple acute nausea and vomiting! "hisis $ecause they $elieve that the condition is not serious enough to #arrant su$ecting

themselves to a visit to the local #hen they are feeling un#ell and #ould prefer $ed

rest! "he availa$ility of +"C domperidone #ould greatly relieve the suffering of thissu$set of patients $y providing more convenient access #ithout compromising the

patientGs safety!

Bo#ever, nausea and vomiting may $e accompanied, for e)ample, $y $lood in the

vomitus, $y fever or pain, or it may $e ongoing or reoccurring! "hese concomitant

symptoms may suggest a serious underlying condition! "he proposed CM' for +"C

domperidone 1see Attachment


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treatment! "his #ill allo# them, in most cases, to return to normal activities uicly!

Easter control and cure rates result in fe#er days lost from #or and therefore greater

productivity in industry! 'n those cases #here the treatment is not successful ; that is ifthe condition has not resolved #ithin *< hours ; the CM' and la$elling advises the patient

to consult a doctor!

Eurthermore, changing domperidone to a estricted 1harmacist +nly Medicine #ill

provide an opportunity for the pu$lic to gain a greater a#areness of the $enefits of this

medicine, thus allo#ing more #idely informed self-sufficient consumers!

'n conclusion, the general pu$lic has a right of access to an effective and safe treatment

for nausea and vomiting that does not usually cause dro#siness or e)trapyramidal

symptoms, #hich are adverse reactions reported for some of the other currently availa$le+"C treatments!

EASEO3SEL34DIA2NOSISORDIA2NOSISB=AP>ARMAIST

Na!sea

Eeelings of nausea can occur in response to a variety of stimulus including food, viral

and $acterial infections, hunger, to)ins, emotions 1such as fear, stress, an)iety, disease

and motion! Most of these are acute, uncomplicated and self-limiting conditions, #hichare suita$le for +"C treatment! 't is for these uncomplicated conditions that domperidone

should $e availa$le to the patient #ithout the need for medical consultation! "he vast

maority of adult mem$ers of the general pu$lic has e)perienced at least one of the a$ove

causes and hence is familiar #ith feeling nauseated!

Causes of nausea #ill $e considered here in t#o sections% those easily self-diagnosed $y

the patient or harmacist, and those #here the cause is unno#n #ithout further medicalinvestigation!

'n most circumstances it is easy to self-diagnose the cause of the nausea $y looing at theacute history, for e)ample recently consumed food, change to medication, high levels of

an)iety or apprehension, or recent contact #ith gastroenteritis! "he proposed CM'

provides clear instructions for appropriate use of the medicine in these acute cases of

nausea #hich are not caused $y a more serious underlying condition!

Bo#ever, reoccurring or prolonged episodes of nausea may suggest a serious underlying

condition for #hich the productGs CM' and la$elling appropriately recommends seeing adoctor!

9o$itin%

"here are several possi$le causes of vomiting! All of these different causes may result in

the comple) seuence of physiological events #hich precede or accompany the act of


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vomiting! "hese include nausea, salivation, ya#ning, and the coordinated respiratory,

gastro-intestinal and a$dominal muscular movements #hich result in retching and

vomiting, accompanied $y changes in $ody posture, cardiovascular function andpsychological state2!

"he cascade of the events associated #ith vomiting maes it an e)perience easilyidentified $y mem$ers of the general pu$lic! 't is very unliely that the patient #ill

mistae the act of vomiting for something else! Although the act itself is not suscepti$le

to misdiagnosis, the consumer may occasionally reuire some assistance #ith thediagnosis of the underlying cause!

>y classifying domperidone as a estricted 1harmacist +nly Medicine, the harmacist

#ould $e availa$le to discuss #ith the consumer any concerns held regarding the durationor severity of the episode, or the occurrence of concomitant symptoms! 'n addition, the

proposed CM' provides clear descriptions of #hen the patient should see further advice

from their harmacist or ! Also, $y limiting the pac si(e to for e)ample ten ta$lets, the

patient #ith chronic symptoms #ould $e forced to return to the pharmacy every t#o andhalf days, allo#ing the harmacist to intervene if reuired! "he harmacist #ould $e a$le

to refer the patient #ith a chronic or reoccurring condition to a for a medicale)amination!

POTENTIAL3ORMASIN2OT>ERSERIOUSONDITIONS

?ausea and vomiting are relatively common symptoms #hich may stem from, or $e

associated #ith, a #ide variety of medical conditions! Many of these are acute, self-

limiting conditions #hich can $e readily treated $y the patient #ith the advice of theharmacist!

Acute non-specific nausea and vomiting 1e!g! Ffood poisoningG, communica$legastroenteritis, motion sicness and hang-over is already esta$lished as a self-medication

indication! atients can $e relied on to diagnose the disorder and, in the maority of

instances, identify the most liely cause! 'n most cases the dehydration and malnutritioncaused $y the symptoms are of more concern than the cause, #hich is usually self-

limiting! 'mportantly, early and convenient access to domperidone could reduce the

amount of electrolytes lost and the possi$ility of dehydration!

atients can also $e relied upon to identify any o$vious further symptoms 1such as $lood

in vomitus, severe headaches, pains, fever or syncope that may indicate a more serious

illness reuiring medical intervention! As a estricted 1harmacist +nly Medicine, theharmacist #ould $e in the position to intervie# the patient a$out concomitant symptoms

and inuire into the length and severity of the episode! harmacists are #ell trained to

counsel patients on nausea and vomiting and are comforta$le #ith intervening anddirecting patients to see their !

2?ausea and Komiting% Mechanism and "reatment! dited $y CJ 4avis, K .ae->aaar and 4 rahame-7mith


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'n addition, appropriate patient information descri$ing the indication symptoms as #ell as

the contraindications, #arnings and precautions for domperidone #ould facilitate self-

diagnosis! "he proposed CM' provides clear information and instructions to ena$le thepatient to use the product correctly and allo# them to recognise more serious symptoms

#hich may reuire medical attention!

"he report prepared $y Medsafe for consideration $y the MCC in March /999 is correct

in stating that the patient may misdiagnose the cause of the nausea and vomiting in some

circumstances! 't is also true that this could lead to the inappropriate or unnecessary useof domperidone! Masing is possi$le as the symptoms may $e ameliorated $ut the

underlying cause can still $e present and untreated! Bo#ever, the possi$ility of masing

is no greater in the case of domperidone than for any other +"C medicine! 'n general, the

types of medicines availa$le +"C do not actually cure their corresponding condition $utsimply alleviate the related symptoms! Dith the maority of +"C medicines amelioration

of the symptoms occurs #ith the underlying cause still $eing present and untreated!

Eurthermore, the danger of masing underlying gastrointestinal conditions cannot $e

considered any greater than for e)ample +"C analgesics possi$ly masing tumours,muscle damage or degenerative $one disorders!

Dhere nausea and vomiting are caused $y a more serious underlying condition, the

symptoms #ill either persist or return after the completion of treatment! 'n this case the

productGs la$elling appropriately directs the consumer to see medical advice! 'f self-medication does $egin inappropriately or unnecessarily, such limited e)posure to

domperidone #ould not $e a maor concern $ecause of the medicineGs favoura$le safety

profile!

Bence, the ris of misdiagnosis is small, and if misdiagnosis does occur and self-

medication $egins, the ris of negative conseuences may $e considered to $e small!

USEINPRE2NAN=

se in pregnancy is of particular interest #ith domperidone $ecause nausea and vomitingor morning sicness are conditions associated #ith pregnancy!

"he M+"'.'M 4ata 7heet 1see Attachment 9 states that domperidone &has only $een

taen $y a limited num$er of pregnant #omen and #omen of child$earing age! "his hasnot resulted in an increase in the freuency of malformation or other direct or indirect

harmful effects on the foetus Hsee also Attachment /0I! A study in rats has sho#n

reproductive to)icity at a high, maternally-to)ic dose! "he potential for humans isunno#n! "herefore, M+"'.'M should only $e used during pregnancy #hen ustified

$y the anticipated therapeutic $enefit!


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According to the Australian categorisation of ris of drug use in pregnancy3,

domperidone is a Category >2 medicine, i!e! a drug hich has $een taen $y only a

limited num$er of pregnant #omen and #omen of child$earing age, #ithout an increasein the freuency of malformation or other direct or indirect harmful effects on the human

fetus having $een o$served!

+ne of the perceived riss of allo#ing anti-nauseants to $e availa$le #ithout a

prescription is the possi$ility of use $y #omen yet to discover they are pregnant!

'mportantly, during the first t#o #ees of development, from conception to the firstmissed period, the em$ryo is considered to $e resistant to any teratogenic effects of

medicines! "he critical period of em$ryonic development, #hen the organ systems

develop, starts at a$out /8 days post-conception and is complete $y 60-80 days 3! After

day /8 the maority of early term pregnant #omen have $een alerted to the possi$ility of$eing pregnant due to a missed period! "he proposed CM' and product la$elling clearly

state that the product should not $e taen if the patient is, or thins she may $e, pregnant!

"hese factors com$ined significantly decrease the chance of a pregnant #oman taing

domperidone! 'mportantly, the possi$ility of inadvertent short term e)posure ofdomperidone in early pregnancy is not detrimental enough to deprive all other patients of

the +"C availa$ility of this useful medicine!

RELE9ANTOMPARATI9EDATA3ORLIEOMPOUNDS

Metoclopramide and prochlorpera(ine are t#o effective treatments for nausea and

vomiting! Metoclopramide is classified as a estricted 1harmacist +nly Medicine #hen

compounded #ith paracetamol in pacs of not more than /0 ta$lets or capsules for the

treatment of nausea associated #ith migraine! rochlorpera(ine is classified as aestricted 1harmacist +nly Medicine #hen sold in pacs containing not more than /0

ta$lets for the treatment of nausea associated #ith migraine!

rometha(ine and dimenhydrinate as #ell as fructose and glucose com$ination products

mae numerous claims relating to nausea and vomiting! Bo#ever domperidone has

demonstrated efficacy in the treatment of nausea and vomiting from any cause!

Metoclopra$i&e

Metoclopramide 5 mg is currently availa$le +"C as a com$ination product #ith 500 mgparacetamol! "his com$ination product, arama):, is indicated for the symptomatic

treatment of migraine! 't is also indicated for the treatment of pain accompanied $y

gastric stasis or nausea and vomiting!

3

3rescri$ing Medicines in regnancy! *thedition, /999! An Australian categorisation of ris of drug use in pregnancy!

Australian 4rug valuation Committee! Common#ealth 4epartment of Bealth and Eamily 7ervices!


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Although the indications for arama) are uite different to those of domperidone and

metoclopramide alone, the presence of metoclopramide in this product maes it an

appropriate medicine for the purposes of comparison to domperidone!

Aerse effects

A listing of the 20< adverse reports received $y CAM for metoclopramide 1as at 30 June

2003 is provided in Attachment *! "he reports for metoclopramide differ significantly, in

terms of num$er and severity of reactions, #ith the /* reports for domperidone up to thesame time point 1see Attachment 3!

Metoclopramide is a dopamine antagonist #ith anti-emetic properties similar to those of

domperidone and certain neuroleptic drugs! Bo#ever, unlie domperidonemetoclopramide readily crosses the $lood-$rain $arrier and induces central anti-

dopaminergic effects in 20L of patients! Karious e)trapyramidal reactions to

metoclopramide, usually of the dystonic type, have $een reported! "hese reactions

include% spasm of the facial muscles trismus rhythmic protrusion of the tongue a $ul$artype of speech spasm of e)traocular muscles including oculogyric crises unnatural

positioning of the head and shoulders and opisthotonos! "here may also $e a generali(edincrease in muscle tone*!

'n contrast, e)trapyramidal symptoms occur only in very rare instances #hen taingdomperidone! Another distinction $et#een metoclopramide and domperidone regarding

this C?7 adverse effect is its onset! )trapyramidal symptoms have $een reported #ith

the long term use of domperidone, #hereas #ith metoclopramide the maority of

reactions occur #ithin 36 hours of starting treatment! Dith $oth medicines thesesymptoms resolve after discontinuation of treatment! "he delay in onset #ith

domperidone gives the medicine a significant $enefit over metoclopramide $ecause it is

only to $e used short term or under medical supervision!

4ue to metoclopramideGs high level of C?7 activity it causes dro#siness, #hich is a #ell

documented adverse reaction! "his impacts on the patientGs a$ility to drive and operatemachinery, carry out normal daily activities, and affects their general feeling of

#ell$eing!

Eurthermore, restlessness, acute depression and diarrhoea have $een reported in patientsreceiving metoclopramide, #hereas restlessness and acute depression are not adverse

reactions associated #ith domperidone! levated serum prolactin levels and galactorrhoea

may occur during therapy #ith either metoclopramide or domperidone!

*Current Ma)olon: 4ata 7heet 1Attachment //!


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Interactions

4omperidone and metoclopramide share the follo#ing interactions%

Action on the gastrointestinal tract is antagonised $y anticholinergics

A$sorption of any concurrently administered oral medication may $e modified $y

their effect on gastric motility!

Bo#ever, metoclopramide and phenothia(ines should only $e prescri$ed concurrently

#ith care, since e)trapyramidal symptoms may occur #ith $oth medicines! Care should

also $e used #hen prescri$ing metoclopramide for patients $eing treated #ith othercentrally active medicines, such as anti-epileptic medicines!

4osing #ith antacids and antisecretory drugs should $e separated from dosing #ithdomperidone $y at least 2 hours! "his is not necessary #ith metoclopramide!

ontrain&ications

4ue to their pharmacology, neither metoclopramide nor domperidone should $e used

#henever stimulation of gastrointestinal motility might $e dangerous, e!g! in the presence

of gastrointestinal haemorrhage, mechanical o$struction or perforation!

Metoclopramide is contraindicated in patients #ith phaeochromocytoma and

domperidone is contraindicated in patients #ith a prolactin-releasing pituitary tumour1prolactinoma!

Prochlorpera*ine

rochlorpera(ine is classified as a estricted 1harmacist +nly Medicine! 'ts +"Cindication is for treatment of nausea associated #ith migraine, ho#ever it is effective for

other causes of nausea!

Aerse effects

rochlorpera(ine, a phenothia(ine, is an effective treatment for nausea and vomiting! 'ts

mechanism of action differs from that of metoclopramide and domperidone! As #ith

metoclopramide, prochlorpera(ine readily crosses the $lood $rain $arrier and can cause

e)trapyramidal symptoms and dro#siness!

"he follo#ing is a discussion of prochlorpera(ine 3 mg! Adverse reactions ofprochlorpera(ine include dry mouth, insomnia, agitation and mild sin reactions! +thereffects #hich have occurred #ith prochlorpera(ine and other phenothia(ine neuroleptics

include aundice, $lood dyscrasias and hyperprolactinaemic effects such as

gynaecomastia! ?euroleptic malignant syndrome 1hyperthermia, rigidity, autonomicdysfunction and altered consciousness may occur #ith any neuroleptic!


- 20 -


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Interactions

Alcohol, $ar$iturates and other sedatives% may intensify the C?7 depressant actions ofprochlorpera(ine! espiratory depression may occur!

Antacids, anti-arinson agents and lithium% interfere #ith a$sorption of

prochlorpera(ine!Antihypertensive agents% prochlorpera(ine may e)aggerate the hypotensive effect of most

antihypertensive drugs, especially alpha-adrenoceptor $locing drugs!

ontrain&ications

rochlorpera(ine should $e avoided in patients #ith% liver dysfunction, prostatic

hypertrophy, epilepsy, no#n hypersensitivity to phenothia(ines, arinsonGs disease,narro# angle glaucoma, and e)isting $lood dyscrasias!

:arnin%s an& preca!tions

Bypotension, usually postural, may occur, particularly in elderly or volume depleted

patients! "ardive dysinesia may occur occasionally, although this is normally associated#ith higher doses than are recommended for >uccastem:! ?ausea and vomiting as a

sign of organic disease may $e mased $y the anti-emetic action of prochlorpera(ine5!

'nterestingly, additional information is contained in the 7temetil: 4ata 7heet dated 23

March /999 1see Attachment /2! Although 7temetil and >uccastem ta$lets are different

strengths, it is not unreasona$le to e)pect significant similarities $et#een 3 mg and 5 mg

prochlorpera(ine! Eor this reason it is important to highlight that 5 mg prochlorpera(ine isalso contraindicated in patients #ith renal dysfunction, hypothyroidism,

phaeochromocytoma and myasthenia gravis! Also, 5 mg prochlorpera(ine has $een

reported to cause hypotension, cardiac arrhythmias, including atrial arrhythmia, A-K$loc, ventricular tachycardia and fi$rillation, and respiratory depression!

Agranulocytosis may occur rarely and it is not dose related!

S!$$ar0 $etoclopra$i&e C prochlorpera*ine #s &o$peri&one

De agree #ith the statement made in the Medsafe report that domperidone is safer than

metoclopramide! 'n contrast, #e reect the vie# that domperidone is not as safe asprochlorpera(ine! "herefore, #e do not accept the reportGs conclusion that domperidone

should remain a rescription Medicine &$ecause there are several other products availa$le

+"C #ith $etter safety profiles 1e!g! >uccastem!

nlie domperidone, prochlorpera(ine causes dro#siness, #hich is a significant adverse

reaction in the +"C environment! 't impacts on the patientGs a$ility to drive and operatemachinery, carry out normal daily activities, and affects their general feeling of

5Current >uccastem: 4ata 7heet 1Attachment /3!


- 2/ -


22/40

#ell$eing! All of these factors place domperidone at an advantage to prochlorpera(ine

regarding safe use $y the consumer!

0cli*ine

Cycli(ine in oral preparations is classified as a harmacy +nly Medicine!

Cycli(ine is an antihistamine #hich is characterised $y a lo# incidence of dro#siness! 't

is indicated for the prevention and treatment of nausea and vomiting caused $y motionsicness, narcotic analgesics, general anaesthetics in the post-operative period and

radiotherapy, especially for $reast cancer since cycli(ine does not elevate prolactin levels!

Cycli(ine may also $e of value in relieving vomiting and attacs of vertigo associated

#ith Menires disease and other forms of vesti$ular distur$ance!

.ie domperidone, cycli(ine should $e should $e used #ith caution in patients #ith

o$structive disease of the gastrointestinal tract! Bo#ever, unlie domperidone, caution

and appropriate monitoring should also $e used #hen cycli(ine is used in patients #ithglaucoma, males #ith possi$le prostatic hypertrophy and patients #ith severe heart

failure!

Potential for a'!se

"he most significant disadvantage of cycli(ine in the +"C setting is its potential for

a$use! 'n some countries the availa$ility of oral cycli(ine formulations as an +"C

medication has led to the misuse of cycli(ine, predominantly $y teenagers! "he aim of

a$users is to produce a state of disoriented e)hilaration associated #ith hallucinations!Misuse may $e $y the oral or intravenous route! "he concomitant misuse of cycli(ine

#ith large amounts of alcohol is particularly dangerous, since the anti-emetic effect of

cycli(ine may increase the to)icity of alcohol6!

Pro$etha*ine

rometha(ine is classified as a estricted 1harmacist +nly Medicine #hen sold in the

manufacturerNs original pac containing not more than /0 doses for the treatment of

insomnia or an)iety! rometha(ine is separately classified as a harmacy +nly Medicine,

e)cept for prometha(ine theoclate #hen sold in a sealed container of not more than /2ta$lets or capsules for the prevention of travel sicness and sold at a transport terminal or

a$oard a ship or plane 1eneral 7ale Medicine!

rometha(ine is a sedating antihistamine #hich has several indications including the

treatment of nausea and vomiting due to several causes! Dhile its efficacy in the

prevention of motion sicness is accepta$le, its efficacy in the treatment of nausea and

6Current Kaloid: 'nection 4ata 7heet 1Attachment /*!


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23/40

vomiting of other origins is lacing in comparison to domperidone, metoclopramide and

prochlorpera(ine!

Aerse effects

"he follo#ing adverse reactions have $een reported for prometha(ine and domperidone%4ry mouth, nausea, vomiting, diarrhoea, constipation, di((iness, urticaria, e)trapyramidal

symptoms 1occurring at a significantly greater freuency than for domperidone

nervousness, and insomnia!

"he follo#ing additional adverse reactions have $een reported for prometha(ine%

pigastric distress, loss of appetite, sedation, restlessness, lassitude, incoordination,

fatigue, $lurred vision, tachycardia, $radycardia, faintness, contact dermatitis 1topical,photosensitisation, angioneurotic oedema, leucopenia, aplastic anaemia,

throm$ocytopenic purpura, aundice, tinnitus, euphoria, convulsive sei(ures, oculogyric

crises, e)citation, catatonic lie states, hysteria, tardive dysinesia, mared irregular

respiration, severe or life-threatening agranulocytosis!

Interactions

rometha(ine may enhance the sedative effects of C?7 depressants 1including alcohol,

$ar$iturates, hypnotics, opioid analgesics, an)iolytic sedatives and neuroleptics!rometha(ine may also interact #ith antimuscarinic drugs 1atropine, tricyclic

antidepressants!

Di$enh0&rinate

4imenhydrinate is classified as a harmacy +nly Medicine, e)cept #hen sold in a sealed

container of not more than /2 ta$lets or capsules for the prevention of travel sicness andsold at a transport terminal or a$oard a ship or plane 1eneral 7ale Medicine!

4imenhydrinate has a significantly different mechanism of action than domperidone!.ie prometha(ine, its efficacy in the prevention of motion sicness is accepta$le!

Bo#ever, its efficacy in the treatment of nausea and vomiting of other origins is also

lacing in comparison to domperidone, metoclopramide and prochlorpera(ine!

Aerse effects

"he follo#ing adverse reactions have $een reported for dimenhydrinate anddomperidone%

di((iness, dry mouth, and nausea!

"he follo#ing additional adverse reactions have $een reported for dimenhydrinate%

dro#siness, lassitude, e)citement and fi)ed drug eruption!


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Interactions

4imenhydrinate may enhance the effects of C?7 depressant type drugs including alcohol,therefore concomitant usage should $e avoided!

3r!ctose an& %l!cose co$'ination pro&!cts

Eructose and glucose have an e)cellent safety profile, #ith the only limitation $eing their

use in dia$etic patients! Dhile very safe, the com$ination product has limited efficacy inthe treatment of nausea and vomiting! 'ts indication simply states that it &may $e of

assistance in the relief of nausea! 't is not intended to treat vomiting!

ONLUSIONS NAUSEAAND9OMITIN2

4omperidone can $e considered appropriate for sale to the general pu$lic as a estricted

1harmacist +nly Medicine for the symptomatic treatment of nausea and vomiting for

the follo#ing reasons%

/! "he general pu$lic can readily recognise the symptoms of nausea and vomiting!

2! "he danger of masing underlying gastrointestinal conditions cannot $e

considered any greater than for e)ample +"C analgesics possi$ly masingtumours, muscle damage or degenerative $one disorders!

3! 4omperidone is #ell tolerated and has a very lo# incidence of adverse events

reported locally and internationally during its e)tensive use since registration in>elgium in /98< and ?e# @ealand in /9


25/40

9! 4omperidone is at least as safe and efficacious as other currently availa$le

estricted 1harmacist +nly Medicines for the treatment of nausea and

vomiting and should $e classified accordingly!


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26/40

PART B+ 1 D=SPEPSIA

BENE3ITS TO BOT> T>E ONSUMER AND TO T>E PUBLI EE

PROPOSED>AN2E

"he risO$enefit of domperidone is demonstra$ly favoura$le and in line #ith that of

esta$lished +"C dyspepsia remedies, many of #hich are unclassified and availa$le

through grocery outlets! "his risO$enefit is not liely to $e adversely affected $ydomperidone $eing made availa$le through pharmacies!

'f this application is successful, it #ill $e to the $enefit of some +"C medicine users #ith

this symptom comple) of dysmotility-lie dyspepsia! "hese sufferers #ill then $e a$le touse a proinetic agent instead of e)isting antacid mi)tures, #hich is more logical and

appropriate for this type of dyspepsia! Bence, domperidone is suita$le for sale as a

estricted 1harmacist +nly Medicine direct to the general pu$lic for the relief of

symptoms associated #ith dysmotility-lie dyspepsia!

EASEO3SEL34DIA2NOSISORDIA2NOSISB=AP>ARMAIST

"he general pu$lic is e)perienced in using +"C medicines to treat dyspepsia! Eor many

years advertising and consumer education campaigns have highlighted the symptoms ofdyspepsia to consumers and it is no# #ell accepted as a condition that is easily and safely

treated #ith +"C medications!

"he term dyspepsia encompasses several symptom comple)es that often overlap! "hreesu$groups of dyspepsia have $een defined! "hese are% ulcer lie, reflu)-lie and

dysmotility-lie! 'n the first t#o categories patients recognise the symptoms of epigastric

discomfort and heart$urn #hilst in the dysmotility group the predominate symptoms arefullness, nausea and $loating after meals!

Clearly, it is the symptoms that the patient recognises and the #ay these symptomsrespond to treatment that are important #hen selecting an appropriate therapy! 7ymptoms

that are related to gastric acid respond #ell to antacids and antisecretory drugs, #hile

those associated #ith dysmotility do not! Conversely, clinical e)perience #ith proinetic

agents suggests that they are successful in relieving the dysmotility comple) ofsymptoms! "herefore, in practice the su$ group of patients #ith dyspepsia are at least

partly defined $y the #ay in #hich they respond to treatment! Eor this reason, an

adeuate description of the target symptoms is an accepta$le #ay of defining the targetpopulation that #ould most $enefit from a proinetic agent!

7ymptoms of dyspepsia are already represented in esta$lished indications for self-medication! A num$er of +"C pharmaceutical products, including Aludro) lus:

suspension, Mucaine:, Mylanta: and Mylanta '': 1Aluminium hydro)ide,

simethicone and magnesium hydro)ide specifically mention dyspepsia as part of their


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la$elling! A range of other +"C stomach remedies, including oter:, "ums: and

Puice(e: also descri$e their effectiveness in dyspepsia using consumer friendly terms

such as feelings of stomach discomfort, including fullness, #ind, heaviness, $loating andnausea! 'n addition, the B2antagonists, Apo-ranitidine:, epcid AC: and "agamet:

are availa$le #ithout prescription for the treatment of symptoms of acid related

dyspepsia!

As evidenced $y e)isting +"C products, it is clear that patients have a long esta$lished

a$ility to correctly recognise the symptoms of dysmotility-lie dyspepsia #ithout medicalsupervision! Appropriate patient information descri$ing the indication symptoms as #ell

as contraindications, #arning and precautions #ill facilitate uality use of this medicine!

"he proposed CM' 1see Attachment


28/40

serious disease and a medical consultation is advisa$le! Eor this reason, #e propose to

limit continuous treatment to t#o #ees 1consistent #ith the la$els for ne#er dyspepsia

treatments!

POTENTIAL3ORMASIN2OT>ERSERIOUSONDITIONS

As discussed previously, dyspepsia is common complaint for #hich patients readily self-

medicate! 4ue to the availa$ility of other +"C medications for this indication, patients

are already encouraged to recognise the signs and symptoms of the disorder and select anappropriate medication for themselves #ith or #ithout the advice of a harmacist!

"he ris of misdiagnosis of dysmotility-lie dyspepsia is small, and if misdiagnosis does

occur and self-medication $egins, the ris of negative conseuences is considered to $esmall! Bo#ever, long term self management of Fgastric painG is not encouraged! 't is

e)tremely difficult to differentiate $et#een such pain and cardiac pain #ithout proper

medical e)amination!

"herefore, +"C domperidone is #ill not $e la$elled for treatment of upper a$dominal

pain, unlie the B2antagonists!

O#erall

Appropriate patient information descri$ing the indication symptoms as #ell as

contraindications, #arnings and precautions #ill facilitate self-diagnosis! "he proposed

CM' provides clear information and instructions to ena$le the patient to use the product

correctly and allo# them to recognise more serious symptoms that may reuire medicalattention! Also harmacists are #ell positioned to intervene and refer these patients to

their for full evaluation if necessary!

RELE9ANTOMPARATI9EDATA3ORLIEOMPOUNDS

>+4Receptor anta%onists ci$eti&ine ranti&ine an& fa$oti&ine

Currently there are three B2antagonists availa$le to the consumer #ithout a prescription

; cimetidine, ranitidine and famotidine!

Cimetidine is classified as a estricted 1harmacist +nly Medicine, #hen sold in the

manufacturerNs original pac containing not more than /* days supply! anitidine and

famotidine are classified as harmacy +nly Medicines, #hen sold in the manufacturerNsoriginal pac containing not more than /* days supply!

All have slightly different approved indications $ut are $asically used for short termsymptomatic relief of indigestion, heart$urn, dyspepsia, e)cess acid 1hyperacidity, and

prevention of these symptoms #hen associated #ith food and drin!


- 2< -


29/40

B2 antagonists are currently the most effective +"C treatment for acid related dyspepsia!

Bo#ever, as discussed previously, they are not as effective as domperidone for the

treatment of dysmotility-lie dyspepsia!

Aerse effects

"he follo#ing adverse reactions have $een reported for cimetidine and domperidone%

4iarrhoea, headache, di((iness, sin rashes and gynaecomastia!

"he follo#ing additional adverse reactions have $een reported for cimetidine%

"iredness, myalgia, reversi$le alopecia, hypersensitivity vasculitis and anaphyla)is,

leuopenia 1including agranulocytosis, throm$ocytopenia, pancytopenia, aplastic

anaemia, confusional states, small increases in plasma creatinine, hepatitis, fever,interstitial nephritis, pancreatitis, sinus $radycardia, tachycardia, heart $loc,

hallucination and depression!

"he follo#ing adverse reactions have $een reported for ranitidine and domperidone%Beadache, nausea, constipation, diarrhoea, a$dominal discomfortOcramps, di((iness,

insomnia raised liver en(ymes and rash!

"he follo#ing additional adverse reactions have $een reported for ranitidine%

Malaise, somnolence, vertigo, reversi$le mental confusion, depression, hallucinations,reversi$le effects on accommodation resulting in $lurred vision, tachycardia, $radycardia,

hypotension, AK $loc, asystole, interstitial nephritis and hepatoto)icity 1#ith or #ithout

aundice, throm$ocytopenia, granulocytosis, neutropenia, aplastic anaemia,

agranulocytosis or panycytopenia, sometimes #ith $one marro# hypoplasia or aplasia,arthralgia, myalgia, hypersensitivity reactions possi$ly resulting in urticaria, fever,

angioneurotic oedema, $ronchospasm, chest pain or anaphylactic shoc and pancreatitis!

egular supervision is recommended for patients taing ?7A'4 concomitantly #ith

ranitidine! anitidine may precipitate acute porphyric attacs and therefore should $e

avoided in patients #ith a history of acute porphyria!

"he follo#ing adverse reactions have $een reported for famotidine and domperidone%

Beadache, di((iness, constipation, diarrhoea, dry mouth, nausea andOor vomiting,

a$dominal discomfort or distension, rash, pruritis, urticaria, insomnia and gynaecomastia!

"he follo#ing additional adverse reactions have $een reported for famotidine%

Anore)ia, fatigue, liver en(yme a$normalities, cholestatic aundice, anaphyla)is,angioedema, arthralgia, muscle cramps, reversi$le psychic distur$ances including

depression, an)iety disorders, agitation, confusion, hallucinations, to)ic epidermal

necrolysis, disorientation, decreased li$ido, paresthesia, somnolence, grand mal sei(ure,pancytopenia, leuopenia, throm$ocytopenia and agranulocytosis!


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Aerse reactions s!$$ar0

As evidenced a$ove, the adverse reactions profiles of cimetidine, ranitidine andfamotidine are all considera$ly less favoura$le than that of domperidone! "hat is,

domperidone can $e considered a safer medicine for short term treatment!

As previously discussed, domperidone is more efficacious than $oth antacids and B2antagonists in treating the dysmotility-lie dyspepsia, and has a $etter adverse reaction

profile than the B2 antagonists that are already availa$le #ithout prescription or consultation! "herefore, #e do not accept the conclusion of the Medsafe report that

domperidone should remain a rescription Medicine &$ecause heart$urn is $etter treated

#ith antacids or B2antagonists #hich are also availa$le +"C!

Interactions

Cimetidine

Cimetidine is #ell no#n for the several drug interactions it causes via the cytochrome*50 1microsomal en(yme system! 't is no#n to have caused clinically significant

changes in the meta$olism of some drugs $y delaying their elimination and thereforeincreasing or prolonging $lood concentrations of these drugs 1for e)ample, #arfarin-type

anticoagulants, phenytoin, theophylline, lidocaine and nifedipine! Bo#ever, a$sorption

of cimetidine is not significantly impaired $y food or $y concomitant administration ofantacids at the usual recommended doses!

anitidine

anitidine does not interact #ith cytochrome *50en(ymes to any clinically significantdegree #hen taen in recommended doses! Bo#ever, sucralfate interferes #ith the

a$sorption of ranitidine and should $e given at least 2 hours after ranitidine!

Eamotidine

Eamotidine does not interact #ith the cytochrome *50 en(yme system! 'n addition,

concomitant use of aluminium hydro)ideOmagnesium hydro)ide at usual doses does notinfluence the pharmacodynamics or $ioavaila$ility of famotidine! Eamotidine does not

affect $lood alcohol levels follo#ing oral ingestion of ethanol!

4omperidoneIn vitro data suggest that the concomitant use of a(ole antifungals, macrolide anti$iotics,

B'K protease inhi$itors and nefa(odone #ith domperidone may result in increased

plasma levels of domperidone! 4omperidone is contraindicated in patients currentlyreceiving oral etocona(ole! 7ince these potential interactions are not supported $y

clinical e)perience, they are unliely to impact on the medicineGs safety in the +"C

environment! All interactions of domperidone can $e adeuately managed $y follo#ingthe proposed CM'!


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ontrain&ications

As #ith domperidone and other medicines, cimetidine, rantidine and famotidine shouldnot $e used in patients #ith a no#n hypersensitivity to the medicine! 'n addition, cross

sensitivity in the B2 antagonist class of compounds has $een o$served! "herefore, once a

patient e)periences hypersensitivity to any of the B2antagonists, other medicines in thisclass cannot $e taen $y the patient!

Potential of >+ anta%onists to $as other serio!s con&itions

"reatment #ith B2 antagonists can mas the symptoms and allo# transient healing of

carcinomas of the stomach, thus delaying correct diagnosis of gastric cancer! "he

potential delay in diagnosis should $e $orne in mind in patients of middle age or older,#ith ne# or recently changed dyspeptic symptoms!

'f patients have difficulty s#allo#ing or if a$dominal discomfort persists or $ecomes

#orse or ne# or additional dyspeptic symptoms develop, the underlying cause should $edetermined! nlie the proposed indication for +"C domperidone, the B2antagonists are

indicated for gastric pain! .ong term self management of gastric pain is not encouraged!"his is $ecause it is e)tremely difficult to differentiate $et#een such pain and cardiac

pain #ithout proper medical e)amination! "hus, the potential for domperidone to mas

other serious underlying conditions is significantly lo#er than for the B2 antagonists#hich are currently classified as estricted 1cimetidine or harmacy +nly 1ranitidine and

famotidine Medicines!

2eneral

As proposed #ith domperidone, therapy #ith B2 antagonists should not e)ceed t#o #ees

of continuous treatment #ithout medical consultation!

Antacids

Antacids are freuently used $y patients to self-treat all types of dyspepsia! Bo#ever, ofthree randomised place$o-controlled studies that have $een reported 8,all failed to sho# a

significant effect of treatment, although there #as improvement in $oth active and

place$o treatment groups, reflecting the high place$o response in the condition!

"herefore, although antacids have a more favoura$le safety profile, their efficacy in anytype of dyspepsia is inadeuate #hen compared to domperidone or B2 antagonists!

8

a otthard , >odemar , >rodin , Jonsson =! "reatment #ith cimetidine, antacid or place$o in patients #ithdyspepsia of unno#n origin! 7candinavian Journal of astroenterology, 23% 8-/ergstrom , ustavsson 7 et al! A$sence of therapeutic $enefit from antacids or

cimetidine in non-ulcer dyspepsia! ?e# ngland Journal of Medicine, 3/*% 339-3*3, /9erstad A! .o#-dose antacids and piren(epine in the treatment of patients #ith non-ulcer dyspepsia and

erosive prepyloric changes! A randomised, dou$le-$lind, place$o-controlled trial! 7candinavian Journal of

astroenterology, 23% 238-2*3, /9


32/40

Opti$al &r!% therap0 of &0s$otilit04lie f!nctional &0spepsia

"he symptoms of dysmotility-lie dyspepsia have a high prevalence in the generalpopulation! Bo#ever, as #ith other types of dyspepsia, only a small proportion of

su$ects #ith these symptoms reuire drug treatment! Medical treatment achieves at least

partial relief of symptoms in the maority of patients!

't is logical and appropriate to use a proinetic agent for patients #ith dysmotility-lie

symptoms! 4omperidone has $een #idely used since its first international approval in>elgium in /98< and ?e# @ealand in /9


33/40

5! 4omperidone is #ell tolerated and has a very lo# incidence of adverse events

reported locally and internationally during its e)tensive use since registration in

>elgium in /98< and ?e# @ealand in /9


34/40

PART B 1 2ENERAL

LOALDATAANDSPEIALONSIDERATIONSRELATIN2TONE:8EALAND

4omperidone 1M+"'.'M /0 mg ta$lets have $een availa$le on prescription in ?e#@ealand since June /9OT>ERMEDIINES

4omperidone may interact #ith anticholinergic medicines as #ell as antacids andantisecretory agents, #hich should not $e given simultaneously #ith domperidone

$ecause these medicines lo#er the $ioavaila$ility of domperidone! 7ince domperidone

has gastro-inetic effects it could influence the a$sorption of concomitantly orally

administered medicines, particularly those of sustained release or enteric-coatedformulations!

'nteraction studies in healthy su$ects have sho#n a mared inhi$ition of domperidoneGsfirst-pass meta$olism $y oral etocona(ole, as evidenced $y an appro)imately three-fold

increase in Cma)and AC of domperidone at steady state and a P"c prolongation of a$out

/0-20 msec! Conseuently, domperidone is contraindicated in patients currently receivingoral etocona(ole!

In vitro data suggest that the concomitant use of a(ole antifungals, macrolide anti$iotics,

B'K protease inhi$itors and nefa(odone #ith domperidone may result in increasedplasma levels of domperidone! Bo#ever, this is not supported $y clinical e)perience!

ONTRAINDIATIONS

4omperidone should not $e used%

in patients #ith no#n hypersensitivity to domperidone

in patients #ith prolactinoma 1a prolactin-releasing pituitary tumour!

in patients currently receiving oral etocona(ole


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35/40

#henever stimulation of gastrointestinal motility might $e dangerous 1such as in

the presence of gastrointestinal haemorrhage, mechanical o$struction or

perforation!

POSSIBLERESISTANE

?one! "he lac of possi$le resistance to domperidone means the usage of the medicine

can increase #ithout impacting negatively on the safety of the community!

T>ERAPEUTIINDEARM

"he availa$ility of domperidone +"C #ill not lead to any community harm resulting

from #ider use of the medicine!


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ONLUSIONS

4omperidone can $e considered appropriate for sale to the general pu$lic as a estricted

1harmacist +nly medicine for the symptomatic treatment of nausea and vomiting and

for the treatment of the symptoms of dysmotility-lie dyspepsia, for the follo#ingreasons%

2ENERAL

/! 4omperidone is #ell tolerated and has a very lo# incidence of adverse events

reported locally and internationally during its e)tensive use since registration in

>elgium in /98< and ?e# @ealand in /9


38/40

D=SPEPSIA

/! "he a$ility of the general pu$lic to recognise and appropriately treat thesymptoms of the various types of dyspepsia is esta$lished #ith the use of other

currently availa$le +"C products! 4omperidone #ill $e used in an essentially

similar manner to these products!

2! "he potential for domperidone to mas other serious underlying conditions is

significantly lo#er than for the B2antagonists, #hich are currently classified asestricted or harmacy +nly Medicines!

3! 't is logical and appropriate to use a proinetic agent for patients #ith

dysmotility-lie symptoms!


- 3< -


39/40

ATTA>MENTS

Attachment / Minute from the 2/stmeeting of the MCC held in March /999

Attachment 2 eport on domperidone prepared $y Medsafe for consideration $y theMCC in March /999

Attachment 3 Adverse reaction reports for domperidone received $y CAM up to 30June 2003, plus line summary details of reports received up to 30

7eptem$er /999

[NB an updated listing has been requested from CARM and will be

provided when this becomes available]

Attachment * Adverse reaction reports for metoclopramide received $y CAM up to

30 June 2003

Attachment 5 Adverse reaction reports for domperidone received $y the "herapeutic

oods Administration 1"A in Australia up to /0 January 2005

Attachment 6 eriodic 7afety pdate eport for domperidone 1M+"'.'M:,

period 02 January 2003 to 0/ January 200*! Johnson Q Johnsonharmaceutical esearch Q 4evelopment, 7A! /< Ee$ruary 200*!

[NB cop of appendices available on request]

Attachment 8 Current approved &rescription Medicine la$elling for M+"'.'M

Attachment < roposed Consumer Medicine 'nformation for +"C M+"'.'M

Attachment 9 Current approved M+"'.'M 4ata 7heet, dated Ee$ruary 2003

Attachment /0 ostmareting surveillance of e)posure to domperidone duringpregnancy! Janssen esearch Eoundation! 28 ?ovem$er /998

Attachment // Current MAR+.+?: 4ata 7heet, dated 29 August 200/ 1acific

harmaceuticals .td

Attachment /2 Current 7"M"'.: 4ata 7heet, dated 5 April 2000 1Aventis

harma .td

Attachment /3 Current >CCA7"M: 4ata 7heet, dated // July 2002 1ecitt

>enciser .td


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Attachment /* Current KA.+'4: 'nection, 4ata 7heet, dated 2* March 200* 1AE"

harmaceuticals .td

Attachment /5 Current @A?"AC: "a$lets Consumer Medicine 'nformation, dated

July 200* 1la)o Dellcome .td

Attachment /6 Current C'4'? M: Consumer Medicine 'nformation, dated

+cto$er 200/ 1Merc 7harp Q 4ohme .td

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