NEW ZEALAND DATA SHEET

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1 1. PRODUCT NAME Dmperidne (Pharmacy Health) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Name and strength f the active substance dmperidne maleate Ph. Eur (equivalent t 10 mg f dmperidne) Excipient(s) with knwn effect Fr the full list f excipients, see sectin PHARMACEUTICAL FORM Oral tablet, uncated Presentatin Dmperidne (Pharmacy Health) are: White rund, bicnvex, uncated tablet with inscriptin Dm 10 n ne side. 4. CLINICAL PARTICULARS 4.1 Therapeutic indicatins Adults and children weighing 35kg Symptmatic treatment f the dyspeptic symptm cmplex that may be assciated with delayed gastric emptying such as epigastric sense f fullness, abdminal distensin r swelling, r epigastric pain r discmfrt. Treatment f acute symptms f nausea and vmiting. There is insufficient evidence t supprt the use f dmperidne in childhd gastresphageal reflux disease. Dmperidne may nt be suitable fr chemtherapy r raditherapy induced nausea and vmiting r pst perative nausea and vmiting. 4.2 Dse and methd f administratin General Dmperidne (Pharmacy Health) shuld be taken minutes befre meals and, if necessary, befre ging t bed at night. If taken after meals, absrptin is smewhat delayed. Adults and children weighing 35 kg New Zealand Data Sheet Page 1 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

2 1 tablet three t fur times daily. The dse f dmperidne shuld be the lwest effective dse fr the individual situatin (typically 30 mg/day). The dse may be increased, if necessary, t a maximum daily ral dse f 40 mg (1 tablet fur times daily). Usually, the maximum treatment duratin shuld nt exceed ne week fr the treatment f acute nausea and vmiting. Fr ther indicatins, the initial duratin f treatment is up t fur weeks. If treatment exceeds fur weeks, patients shuld be re evaluated and the need fr cntinued treatment re assessed. Fr children, the ttal daily dse has been determined as 0.25 mg/kg three t fur times per day with a maximum daily dse f 1.0 mg/kg. Hwever, the dmperidne tablet frmulatin is unsuitable fr treatment in children weighing less than 35 kg. Use in children under 2 years f age is cntraindicated (see Sectin 4.3 Cntraindicatins). Since mnths f life, the risk f neurlgical side effects is higher in yung children (see Sectin 4.8 Undesirable effects). Overdsing may cause nervus system disrders in children (see Sectin 4.9 Overdse). Use in renal impairment It is unlikely that the dse needs t be adjusted fr single administratin in patients with renal insufficiency. Hwever, since the eliminatin half life f dmperidne is prlnged in severe renal impairment, n repeated administratin the dsing frequency f dmperidne shuld be reduced t nce r twice daily depending n the severity f the impairment (see Sectin 4.4 Special warning and precautins fr use). Generally, patients n prlnged therapy shuld be reviewed regularly. 4.3 Cntraindicatins Dmperidne (Pharmacy Health) is cntraindicated in the fllwing situatins: Knwn hypersensitivity t dmperidne r any f the excipients. Prlactin releasing pituitary tumur (prlactinma). Use in children under 2 years f age. C administratin with ptent CYP3A4 inhibitrs has been shwn t increase dmperidne cncentratins t the pint where QT interval prlngatin may ccur. Examples f ptent CYP3A4 inhibitrs include sme azle antifungals (eg, intracnazle, vricnazle, psacnzazle), sme macrlide antibitics (eg, clarithrmycin, telithrmycin), and sme prtease inhibitrs (ritnavir, saquinavir, telaprevir). C administratin with medicines that prlng the QTc interval. dmperidne shuld nt be used whenever stimulatin f gastrintestinal mtility might be dangerus such as in the presence f gastrintestinal haemrrhage, New Zealand Data Sheet Page 2 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

3 mechanical bstructin, r perfratin. In patients with mderate r severe hepatic impairment (see Sectin 5.2 Pharmackinetic prperties). 4.4 Special warnings and precautins fr use Cardivascular effects Dmperidne shuld be used with cautin in lder patients r thse with current r histry f cardiac disease. An increase in the risk f serius ventricular arrhythmias and sudden cardiac death has been reprted in epidemilgy studies (see Sectin 4.8 Undesirable effects - Pst marketing). Thse studies suggest this increased risk may be higher in patients lder than 60 years r at ttal daily dses f mre than 30mg. Dmperidne shuld be used at the lwest effective dse in adults and children. Treatment with dmperidne shuld be stpped if signs r symptms ccur that may be assciated with cardiac arrhythmia, and the patient shuld cnsult their physician. Use f dmperidne and ther drugs which prlng QTc intervals requires that cautin be exercised in patients wh have existing prlngatin f cardiac cnductin intervals, particularly QTc, patients with significant electrlyte disturbances r underlying cardiac diseases such as cngestive heart failure. Other risk factrs fr sudden cardiac arrest include a family histry f crnary artery disease, high bld pressure, high bld chlesterl, besity, diabetes, smking and excessive alchl cnsumptin. It is desirable t ptimise electrlyte levels prir t starting dmperidne. Drug interactin ptential The main metablic pathway f dmperidne is thrugh CYP3A4. In vitr and human data shw that the cncmitant use f drugs that significantly inhibit this enzyme may result in increased plasma levels f dmperidne. C administratin f dmperidne with ptent CYP3A4 inhibitrs which have been shwn t cause QT interval prlngatin is cntraindicated (see Sectin 4.3 Cntraindicatins). Cautin shuld be exercised when dmperidne is c administered with ptent CYP3A4 inhibitrs which have nt been shwn t cause QT interval prlngatin such as indinavir and patients shuld be mnitred clsely fr signs r symptms f adverse reactins (see Sectin 4.8 Undesirable effects). Cautin shuld be exercised when dmperidne is c administered with drugs which have been shwn t cause QT interval prlngatin and patients shuld be mnitred clsely fr signs r symptms f cardivascular adverse reactins (see Sectin 4.8 Undesirable effects). Examples include: anti arrhythmics class IA (e.g., dispyramide, quinidine) anti arrhythmics class III (e.g., amidarne, dfetilide, drnedarne, ibutilide, stall) certain antipsychtics (e.g., halperidl, pimzide, sertindle) certain antidepressants (e.g., citalpram, escitalpram) New Zealand Data Sheet Page 3 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

4 certain antibitics (e.g., levflxacin, mxiflxacin) certain antifungal agents (e.g., pentamidine) certain antimalarial agents (e.g., halfantrine) certain azle antifungals, (e.g., itracnazle, ketcnazle, vricnazle) certain calcium antagnists, (e.g., diltiazem, verapamil) certain gastr intestinal drugs (e.g., dlasetrn) certain HIV prtease inhibitrs (e.g., amprenavir, atazanavir, fsamprenavir, indinavir, nelfinavir, ritnavir, saquinavir) certain drugs used in cancer (e.g., tremifene, vandetanib) certain macrlide antibitics (e.g., clarithrmycin, erythrmycin) certain ther drugs (e.g., aprepitant, bepridil, methadne, nefazdne, telithrmycin) Antacids r antisecretry agents shuld nt be taken simultaneusly with Dmperidne, as they lwer the ral biavailability f dmperidne (see Sectin 4.5 Interactins). When used cncmitantly, dmperidne shuld be taken befre meals and antacids r antisecretry agents after meals. Intlerance t lactse The film cated tablets cntain lactse and may be unsuitable fr patients with lactse intlerance, galactsemia r glucse/galactse malabsrptin. Prlactin levels Dmperidne prduces an increase in plasma prlactin. The raised level persists with chrnic administratin but falls t nrmal n discntinuing the medicine. During chrnic ral administratin f 30 mg daily fr tw weeks the plasma prlactin level measured 90 minutes after medicine intake remained fairly cnstant at 25 ng/ml in males (nrmal value was 5 ng/ml) whilst in females the level f 117 ng/ml after the first dse decreased t 56 ng/ml after 14 dses (pretreatment nrmal value was 9 ng/ml). Tissue culture experiments indicate that apprximately ne third f human breast cancers are prlactin dependent in vitr, a factr f ptential imprtance if the administratin f dmperidne is cntemplated in a patient with a past histry f breast cancer. Althugh disturbances such as galactrrhea, amenrrhea, gynaecmastia and imptence have been reprted with ther prlactin elevating medicines, the clinical significance f elevated serum prlactin levels is unknwn. An increase in mammary neplasms has been fund in rdents after chrnic administratin f dmperidne and ther prlactin stimulating medicines. Neither clinical studies nr epidemilgical studies cnducted t date have shwn an assciatin between chrnic administratin f these medicines and mammary tumrigenesis. Dmperidne des nt affect plasma grwth hrmne r aldsterne levels. Carcingenicity, Mutagenicity, Teratgenicity New Zealand Data Sheet Page 4 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

5 Dmperidne was administered t mice fr 18 mnths and rats fr 24 mnths in carcingenicity studies. N dse related effects were bserved except fr an increased incidence f malignant mammary tumurs at 25 times the maximum human dse in female mice and rats and an increased incidence f pituitary tumurs at 25 times the human dse in male rats. N evidence fr mutagenic ptential was seen in dminant lethal studies in male and female mice, micrnucleus tests in female mice and female rats, a study f chrmsmal aberratins in human lymphcytes, a sex linked recessive lethal test n Drsphila melangaster, and in the Ames metablic activatin test with Salmnella typhimurium. Minr teratgenic effects were seen in ne study where dmperidne was administered t rats rally at apprximately 125 times the maximum human dse level. These findings were nt cnfirmed by anther study where the medicine was administered rally t rats at dsage levels as high as 400 times than that given t man. Embrytxicity withut maternal txicity was encuntered when dmperidne was administered intravenusly t rats (> 6 times the maximum human dse level) and rally t mice (44 times the maximum human dse level). Cncurrent embrytxicity and maternal txicity were incnsistently fund at ral dse levels apprximately 6 times the maximum human level in rabbits and in rats and apprximately 24 times the maximum human dse level. Renal impairment Since the eliminatin half life f dmperidne is prlnged in severe renal impairment, the dsing frequency f dmperidne shuld t be reduced t nce r twice daily depending n the severity f the impairment. The dse may als need t be reduced. Such patients with severe renal impairment shuld be reviewed regularly (see Sectin 5.2 Pharmackinetics and Sectin 4.2 Dsage and Administratin). Hepatic Impairment Dmperidne is cntraindicated fr patients with mderate r severe hepatic impairment (see Sectin 4.3 Cntraindicatins). Dse adjustment is nt required fr patients with mild hepatic impairment (see Sectin 5.2 Pharmackinetics). Infants Dmperidne tablets are unsuitable fr use in children weighing less than 35 kg. Since metablic functins and the bld brain barrier are nt fully develped in the first mnths f life the risk f neurlgical side effects is higher in yung children (see Sectin 4.8 Undesirable effects). Therefre it is recmmended that the dse be determined accurately and fllwed strictly in tddlers and small children. Overdsing may cause nervus system disrders in children, but ther causes shuld be taken int cnsideratin. 4.5 Interactin with ther medicines and ther frms f interactin New Zealand Data Sheet Page 5 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

6 Cncmitant administratin f antichlinergic drugs may antagnise the anti dyspeptic effect f dmperidne. If administered prir t atrpine, dmperidne reduces the relaxant effect f atrpine upn the lwer esphageal sphincter, but has n reversing effect if atrpine is administered first. The main metablic pathway f Dmperidne is thrugh the cytchrme P450 isenzyme CYP3A4. In vitr and human data shw that the cncmitant use f drugs that significantly inhibit this enzyme may result in increased plasma levels f dmperidne. When Dmperidne was c administered with ptent CYP3A4 inhibitrs which have been shwn t cause QT interval prlngatin, clinically relevant changes in QT intervals were bserved. Therefre, c administratin f dmperidne with certain drugs is cntraindicated (see Sectin 4.3 Cntraindicatins). Cautin shuld be exercised when dmperidne is c administered with ptent CYP3A4 inhibitrs which have nt been shwn t cause QT interval prlngatin r drugs which have been shwn t cause QT interval prlngatin (see Sectin 4.4 Special warnings and precautins fr use). Theretically, since dmperidne has gastr kinetic effects, it culd influence the absrptin f cncmitantly rally administered drugs, particularly thse with sustained release r entericcated frmulatins. Hwever, in patients already stabilised n digxin r paracetaml, cncmitant administratin f dmperidne did nt influence the bld levels f these drugs. Dmperidne has been used with: neurleptics, withut ptentiatin f their activity, dpaminergic agnists (brmcriptine, L dpa) fr suppressin f unwanted peripheral effects such as digestive disrders, nausea and vmiting, withut affecting their central activity. 4.6 Fertility, pregnancy and lactatin Pregnancy There are limited pst marketing data n the use f dmperidne in pregnant wmen. A study in rats has shwn reprductive txicity at a high, maternally txic dse. The ptential risk fr humans is unknwn. Therefre, dmperidne shuld nly be used during pregnancy when justified by the anticipated therapeutic benefit. Lactatin The amunt f dmperidne that culd be ingested by an infant thrugh breast milk is lw. The maximal relative infant dse (%) is estimated t be abut 0.1% f the maternal weight adjusted dsage. It is nt knwn whether this is harmful t the newbrn. Therefre, breast feeding is nt recmmended fr wmen wh are taking dmperidne. New Zealand Data Sheet Page 6 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

7 4.7 Effects n ability t drive and use machines Dizziness and smnlence have been bserved fllwing use f dmperidne (see Sectin 4.8 Undesirable effects). Therefre, patients shuld be advised nt t drive r use machinery r engage in ther activities requiring mental alertness and crdinatin until they have established hw dmperidne affects them. 4.8 Undesirable effects Reprting suspected adverse reactins after authrisatin f the medicine is imprtant. It allws cntinued mnitring f the benefit/risk balance f the medicine. Healthcare prfessinals are asked t reprt any suspected adverse reactins In additin t the adverse effects reprted during clinical studies (see Sectin 5.3 Preclinical safety data), the fllwing adverse drug reactins have been reprted (Tables 3 and 4). In each table, the frequencies are prvided accrding t the fllwing cnventin: Very cmmn 1/10 Cmmn 1/100 and < 1/10 Uncmmn 1/ 1,000 and < 1/100 Rare 1/10,000 and < 1/1,000 <1/10,000, including islated reprts. In Table 1, ADRs are presented by frequency categry based n spntaneus reprting rates, when knwn. Table 1. Adverse Drug Reactins Identified During Pst marketing Experience with dmperidne by Frequency Categry Estimated frm Spntaneus Reprting Rates Immune System Disrders Psychiatric Disrders Nervus System Disrders Cardiac Disrders Skin and Subcutaneus Tissue Disrders Renal and Urinary Disrders Reprductive System and Breast Disrders Rare Investigatins Anaphylactic Reactin (including Anaphylactic Shck) Agitatin, Nervusness Dizziness, Extrapyramidal Disrder, Cnvulsin Sudden Cardiac Death*, Serius Ventricular Arrhythmias* Angiedema, Urticaria Urinary Retentin Gynaecmastia, Amenrrhea Liver Functin Test Abnrmal, Bld Prlactin Increased New Zealand Data Sheet Page 7 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

8 * Based n epidemilgy data (see belw) case reprts f QTc prlngatin, ventricular arrhythmia, and sudden death have ccurred with dmperidne use. Althugh mst reprted cases have ccurred in patients receiving the intravenus frm f dmperidne, r in patients with ther risk factrs, an assciatin with ral dmperidne cannt be cmpletely ruled ut. Therefre, dmperidne shuld be used with cautin in patients with ther risk factrs fr QTc prlngatin including hypkalaemia, severe hypmagnesaemia, structural heart disease, the cncmitant administratin f QTc prlnging medicines, r an underlying genetic predispsitin. Extrapyramidal disrder ccurs primarily in nenates and infants. Other central nervus system related effects f cnvulsin and agitatin als are reprted primarily in infants and children. An increase in the risk f serius ventricular arrhythmias and sudden cardiac death has been reprted in sme epidemilgy studies. The risk may be higher in patients lder than 60 years r at ttal daily dses f mre than 30mg. Dmperidne shuld be used at the lwest effective dse in adults and children. Due t the limitatins f these data, the exact frequency f these adverse reactins culd nt be defined. Paediatric ppulatin In pst marketing experience, there were n differences in the safety prfile f adults and children, with the exceptin f extrapyramidal disrder which ccurred primarily in nenates and infants (up t ne year f age), and ther central nervus system related effects f cnvulsin and agitatin which were reprted primarily in infants and children. 4.9 Overdse Fr advice n the management f verdse please cntact the Natinal Pisns Centre n 0800 POISON ( ). Symptms and signs Overdse has been reprted primarily in infants and children. Symptms f verdse may include agitatin, altered cnsciusness, cnvulsin, disrientatin, smnlence and extrapyramidal reactins. Treatment There is n specific antidte t dmperidne, but in the event f a large verdse, gastric lavage within ne hur f ingestin as well as the administratin f activated charcal may be useful. Antichlinergics, anti Parkinsnian agents may be helpful in cntrlling the extrapyramidal reactins. Clse bservatin and supprtive therapy is recmmended. New Zealand Data Sheet Page 8 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

9 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacdynamic prperties Mechanism f Actins Dmperidne is a dpamine antagnist with antiemetic prperties. Dmperidne des nt readily crss the bld brain barrier. It seldm causes extrapyramidal side effects, but des cause a rise in prlactin levels. Its antiemetic effect may be due t a cmbinatin f peripheral (gastrkinetic) effects and antagnism f central dpamine receptrs in the chemreceptr trigger zne which lies in the area pstrema and is regarded as being utside the bld brain barrier. It als antagnises the behaviural effects f dpamine much mre effectively when administered intracerebrally than when given systemically. These findings, tgether with the lw cncentratins fund in the brain, indicate a predminantly peripheral effect f dmperidne n dpamine receptrs. Studies in humans have shwn intravenus and ral dmperidne t increase lwer esphageal pressure, imprve antrdudenal mtility and accelerate gastric emptying. Dmperidne has n effect n gastric secretin. Effect n QT/QTc Interval and Cardiac Electrphysilgy In accrdance with ICH E14 guidelines, a thrugh QT study was perfrmed in healthy subjects. This study included a placeb, active cmparatr and psitive cntrl and was cnducted using recmmended therapeutic dses (10 r 20 mg administered 4 times a day). This study fund a maximal difference f QTc between dmperidne and placeb in LS means in the change frm baseline was 3.4 msec fr 20 mg dmperidne administered 4 times a day n Day 4, and the 2 sided 90% CI ( msec) did nt exceed 10 msec. The QT prlngatin bserved in this study when dmperidne was administered accrding t the recmmended dsing is nt clinically relevant. This lack f clinical relevance is crrbrated by pharmackinetics and QTc interval data frm tw lder studies which invlved a 5 day treatment f 20 mg and 40 mg dmperidne administered 4 times a day. ECGs were recrded prir t the study, n Day 5 at 1 hur (apprximately at tmax) after the mrning dse, and 3 days later. In bth studies, n difference between QTc after active treatment and placeb was bserved. It was therefre cncluded that cncentratins f dmperidne after 80 and 160 mg daily had n clinically significant effect n QTc in healthy subjects. 5.2 Pharmackinetic prperties New Zealand Data Sheet Page 9 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

10 Absrptin: in fasting subjects, dmperidne is rapidly absrbed fllwing ral administratin with peak plasma cncentratins ccurring at apprximately 30 t 60 minutes. The lw ral biavailability (apprximately 15%) is due t extensive first pass metablism in the gut wall and liver. Althugh the biavailability f dmperidne is enhanced in nrmal subjects when taken after a meal, patients with gastr intestinal cmplaints shuld take dmperidne 15 t 30 minutes befre a meal. Oral biavailability f dmperidne base is decreased by prir cncmitant administratin f cimetidine and sdium bicarbnate (see Sectin 4.5 Interactins with ther medicines and ther frms f interactin). The time f peak absrptin is slightly delayed and the AUC smewhat increased when the ral medicine is taken after a meal. Distributin: Oral dmperidne des nt appear t accumulate r induce its wn metablism; a peak plasma level after 90 minutes f 21 ng/ml after tw weeks ral administratin f 30 mg per day was almst the same as that f 18 ng/ml after the first dse. Dmperidne is 91 t 93% bund t plasma prteins. Distributin studies with radi labelled drug in animals have shwn wide tissue distributin, but lw brain cncentratin. Small amunt f drug crss the placenta in rats. Metablism: Dmperidne underges rapid and extensive hepatic metablism by hydrxylatin and N dealkylatin. In vitr metablism experiments with diagnstic inhibitrs revealed that CYP3A4 is a majr frm f cytchrme P 450 invlved in the N dealkylatin f dmperidne, whereas CYP3A4, CYP1A2 and CYP2E1 are invlved in dmperidne armatic hydrxylatin (see Sectin 4.5 Interactins with ther medicines and ther frms f interactin). Eliminatin: Urinary and faecal excretin amunts t 31 and 66%, respectively, f the ral dse. The prprtin f the medicine excreted unchanged is small (10% f faecal excretin and apprximately 1% f urinary excretin). The plasma half life after a single ral dse is 7 9 hurs in healthy subjects but is prlnged in patients with severe renal insufficiency. Special Ppulatins Hepatic Impairment: in subjects with mderate hepatic impairment (Pugh scre 7 t 9, Child Pugh rating B), the AUC and Cmax f dmperidne is 2.9 and 1.5 fld higher, respectively, than in healthy subjects. The unbund fractin is increased by 25%, and the terminal eliminatin half life is prlnged frm 15 t 23 hurs. Subjects with mild hepatic impairment have a smewhat lwer systemic expsure than healthy subjects based n Cmax and AUC, with n change in prtein binding r terminal half life. Subjects with severe hepatic impairment were nt studied (see Sectin 4.3 Cntraindicatins). Renal impairment: in studies with severe renal insufficiency (serum creatinine > 6 mg/100 ml, i.e., > 0.6 mml/l) the half life f dmperidne is increased frm 7.4 t 20.8 hurs, but plasma drug levels are lwer than in subjects with nrmal renal functin. Very little unchanged drug (apprximately 1%) is excreted via the kidneys (see Sectin 4.4 Special warning and New Zealand Data Sheet Page 10 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

11 precautins). Paediatric Patients: based n the limited pharmackinetic data, dmperidne plasma cncentratin in preterm nenates were cnsistent with thse reprted in adults. 5.3 Preclinical safety data Clinical Trial Data The safety f dmperidne was evaluated in 1221 patients with gastrparesis, dyspepsia, gastr esphageal reflux disrder (GERD), r ther related cnditins in 45 clinical trials included in the safety database. All patients were 15 years ld and received at least ne dse f ral Dmperidne. Slightly fewer than ne half (553/1221) f patients were diabetic. The median ttal daily dse was 80 mg (range 10 t 160 mg), with 230 patients receiving a dse greater than 80 mg. Median duratin f expsure was 56 days (range 1 t 2248 days). Table 2. Adverse Reactins Reprted by 1% f dmperidne Treated Patients in 45 Clinical Trials System/Organ Class Adverse Reactin Psychiatric Disrders dmperidne (n=1221) % Depressin 2.5 Anxiety 1.6 Libid Decreased/Lss f Libid 1.5 Nervus system disrders Headache 5.6 Smnlence 2.5 Akathisia 1.0 Gastrintestinal Disrders Diarrhea 5.2 Skin and Subcutaneus Tissue Disrders Rash 2.8 Pruritus 1.7 Reprductive System and Breast Disrders Breast Enlargement/Gynaecmastia 5.3 Breast Tenderness 4.4 Galactrrhea 3.3 Amenrrhea 2.9 Breast Pain 2.3 Amenrrhea 2.9 Breast Pain 2.3 Menstruatin Irregular 2.0 Lactatin Disrder 1.6 New Zealand Data Sheet Page 11 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

12 General Disrders and Administratin Site Cnditins Asthenia 1.9 AD ADRs that ccurred in < 1% f dmperidne treated patients in the 45 clinical trials (n=1221) are listed belw in Table 3 Table 3. Adverse Reactins Reprted by 1% f dmperidne Treated Patients in 45 Clinical Trials System/Organ Class Adverse Reactin Immune System Disrder dmperidne (n=1221) % Hypersensitivity 0.2 Skin and Subcutaneus Tissue Disrders Urticaria 0.7 Reprductive System and Breast Disrders Breast Discharge 0.8 Breast Swelling 0.5 The fllwing adverse reactin has been reprted with ver the cunter use: dry muth. 6. PHARMACEUTICAL PARTICULARS 6.1 List f excipients Lactse Starch-Maize Cellulse - Micrcrystalline Pvidne Sdium lauryl sulphate Silica Cllidal Anhydrus Magnesium stearate Purified Water 6.2 Incmpatibilities In the absence f cmpatibility studies, this medicine must nt be mixed with ther medicines. 6.3 Shelf life 3 years when stred at r belw 30 C New Zealand Data Sheet Page 12 f 13 Dmperidne (Pharmacy Health) 0218 v2.0

13 6.4 Special precautins fr strage Stre belw 30 C Stre in riginal cntainer. 6.5 Nature and cntents f cntainer Blister pack f 25*, 30* and 100 tablets. NEW ZEALAND DATA SHEET * nt all pack sizes may be marketed 6.6 Special precautins fr dispsal <and ther handling> Any unused medicine r waste material shuld be dispsed f in accrdance with lcal requirements. 7. MEDICINE SCHEDULE Prescriptin Medicine 8. SPONSOR PSM Healthcare Ltd t/a API Cnsumer Brands Ltd Nrman Spencer Drive PO Bx Manukau Auckland 2241 Phne DATE OF FIRST APPROVAL 24 th May DATE OF REVISION OF THE TEXT n/a SUMMARY TABLE OF CHANGES Sectin changes All sectins Summary f new infrmatin New. New Zealand Data Sheet Page 13 f 13 Dmperidne (Pharmacy Health) 0218 v2.0