DOMPERIDON

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DOMPERIDON

NAMA GENERIKDomperidon

NAMA KIMIA5-Chloro-l-{l-[3-(2-oxobenzimidazolin-l-yl)propyl]-4-piperidyl}benzimidazolin-2-one.

STRUKTUR KIMIAC22H24ClN5O2

SIFAT FISIKOKIMIASerbuk warna putih atau hampir putih, polimorfisa. Praktis tidak larut dalam air, sedikit larutdalam alkohol dan metanol, larut dalam dimetilforfamide.

SUB KELAS TERAPI

Obat Untuk Saluran Cerna

FARMAKOLOGIAbsorpsi (1) : Per oral : Bioavailabilitas 13-17%. Rendahnya bioavailabitas sistemik ini

disebabkan oleh metabolisme lintas pertama di hati dan metabolisme pada dinding usus.;Pengaruh metabolisme pada dinding usus jelas terlihat pada adanya peningkatan bioavailabilitas

dari 13% ke 23% jika Domperidon tablet diberikan 90 menit sebelum makan dibandingkan jika

diberikan dalam keadaan perut kosong. ;Konsentrasi puncak dicapai dalam waktu 30-110 menit.

Waktu untuk mencapai konsentrasi puncak lebih lama jika obat diminum sesudah makan. Perrektal : Bioavailabilitas 12%. Konsentrasi puncak dicapai dalam waktu 1 jam;Distribusi (1) : 91-

93% terikat pada protein plasma. Volume distribusi : 5,71 L/kg;Metabolisme (1) : terutama di

hati (metabolisme lintas pertama);Eliminasi (1,5) : waktu paruh eliminasi : 7-9 jam. Sekitar 30%dari dosis oral diekskresi lewat urine dalam waktu 24 jam. Hampir seluruhnya diekskresi sebagai

metabolit.;Sisanya diekskresi dalam feses dalam beberapa hari, sekitar 10% sebagai bentuk yang

tidak berubah

STABILITAS PENYIMPANANSimpan dalam wadah terlindung dari cahaya.

KONTRA INDIKASIProlaktinoma, gangguan hati, dimana peningkatan motilitas gastro-intestinal dapat

berbahaya;Hipersensitif terhadap Domperidon.

EFEK SAMPINGGangguan gastrointestinal termasuk kram (jarang), efek ekstrapiramidal (sangat jarang), dan

kemerahan pada kulit.;Hiperprolaktinemia / terjadi peningkatan konsentrasi prolaktin plasma,

yang menyebabkan galactorrhoea atau gynaecomastia.

INTERAKSI OBATAnalgesik opioid dan antimuskarinik memberikan efek antagonis terhadap efek prokinetik dari


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Domperidon.;Domperidon dimetabolisme melalui cytochrome P450 isoenzyme CYP3A4;

penggunaan bersama dengan Ketoconazole telah dilaporkan meningkatkan kadar plasma

Domperidon 3 kali lipat dan sedikit penambahan panjang interval QT. ;Risiko aritmia padaDomperidon juga meningkat jika digunakan bersama Ketoconazol.3 Inhibitor CYP3A4 yang

poten seperti Erythromycin atau Ritonavir juga meningkatkan konsentrasi Domperidon, sehingga

sebaiknya kombinasi ini dihindari.;Absorpsi oral Domperidon menurun jika sebelumnyadiberikan Cimetidine 300 mg atau larutan Sodium bikarbonat.Domperidon merupakan antagonisefek hipoprolaktinemia dari Bromkokriptin.

PENGARUH HASIL LABMeningkatkan serum Thyroid Stimulating Hormone.

PENGARUH KEHAMILANKategori C.;Tidak diketahui apakah Domperidon melewati plasenta. Data pada manusia masih

terbatas, namun data pada hewan menunjukkan adanya risiko. ;Toksisitas berat yang terkait

dengan dosis telah dilaporkan terjadi pada orang dewasa dan obat ini tidak disetujui oleh FDA

untuk digunakan di USA.;Pihak produsen menyarankan sebaiknya dihindari penggunaannyaselama kehamilan.

PENGARUH MENYUSUISejumlah kecil Domperidon diekskresikan melalui ASI, tetapi dilaporkan tidak ada efek samping

pada bayi. Domperidon telah digunakan untuk menstimulasi produksi ASI karena kerjanyameningkatkan konsentrasi prolaktin. ;Data pada manusia masih terbatas. The American

Academy of Pediatric menggolongkan obat ini dapat digunakan pada ibu menyusui. Meskipun

demikian, karena Domperidon berpotensi menimbulkan toksisitas yang serius pada ibu,

;disarankan untuk memilih alternatif lain yang lebih aman.

BENTUK SEDIAANTablet/Film Coated Tablet 10 mg, Suspensi 5 mg / 5 ml, Sirup 5 mg / 5 ml, Oral drops 5 mg/ml

PERINGATANPenyesuaian dosis diperlukan pada pasien yang mendapat Domperidon bersama dengan

Simetidine;Tidak dianjurkan untuk pemakaian jangka panjang atau pencegahan rutin mual-

muntah pasca operasi.

MEKANISME AKSIDomperidon merupakan antagonis dopamin, yang memblok reseptor D1 dan D2. ;Dopamin

memfasilitasi aktivitas otot halus gastrointestinal dengan menghambat dopamin pada reseptor D1

dan menghambat pelepasan asetilkolin netral dengan memblok reseptor D2.;Domperidonmerangsang motilitas saluran cerna bagian atas tanpa mempengaruhi sekresi gastrik, empedu dan

pankreas. Peristaltik lambung meningkat sehingga dapat mempercepat pengosongan lambung

Domperidone: Obat Antiemetika (Antimuntah)
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Nama Dagang:DOM (Lapi), Dombaz (Zenith Pharma), Domedon (Tempo ScanPacific), Domet (Hexpharm), Dometa (Ikapharmindo), Dominal (Actavis), Galflux(Guardian), Gerdilium (Otto), Monell (Novell Pharma), Motilium (Janssen-Cilag), Novotil(Sandoz), Regit (Landson), Tilidon (Interbat), Vesperum (Ifars), Vomecho, Vomerin(Soho), Vometa (Dexa Medica), Vomidone (Pharos), Vomistop (Gracia Pharmindo),

Vomitas (Kalbe Farma), Vosedon (Sanbe), Yaridon (yarindo).

Formulasi: Tablet Salut Selaput, Tablet Fast Disintegrating & Sirup (Suspensi)Tiap 100 ml suspensi mengandung:Domperidone 1 mg/mlGliserin 20 mlMetilselulosa 50 mlParaben 0.1%

Aquadest ad 100 ml

Farmakologi:Domperidone (5-chloro-1-(1-[3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-

1-yl)propyl]piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one) merupakan antagonisdopamine derivate benzimidazol yang mempunyai potensi sebagai antiemetika karenaadanya kombinasi efek perifer (sebagai gastrokinetik) dan antagonis reseptor dopaminepada chemoreceptor trigger zone yang terletak di luar sawar darah otak.

Farmakodinamik:Domperidone memperlama kontraksi antro-duodenal, mempercepatpengosongan lambung dan meningkatkan tekanan springter esophagus bagian bawah.Domperidone tidak memberikan efek pada sekresi lambung.

Kontraindikasi:Pada pasien yang mengalami peningkatan motilitas lambung,domperidone dapat menyebabkan pendarahan, perforasi atau obstruksi mekanik serta

pasien dengan tumor hipofise yang mengeluarkan prolaktin.

List Excipients :

Sorbitol solution 70% non crystallizable

Microcrystalline cellulose and carmellose sodium

Methyl p-hydroxybenzoate

Propyl p-hydroxybenzoate

Sodium saccharin

Polysorbate 20

Sodium hydroxide


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Purified water.

Excipients with known effect:

Sorbitol2.275g/5ml

Methyl hydroxybenzoate9.000mg/5ml

Propyl hydroxybenzoate1.000mg/5ml

MOTILIUM 1 mg/mL suspension.

SCHEDULING STATUS

Schedule 2.

PROPRIETARY NAME(and dosage form)

MOTILIUM1 mg/mL suspension.

COMPOSITION

Each mL contains 1 mg domperidone, with 0,18 % m/v methylparaben and 0,02 % m/v propylparaben as

preservatives.

PHARMACOLOGICAL CLASSIFICATION

A.5.7.2 Anti-emetics and anti-vertigo preparations.

PHARMACOLOGICAL ACTION

Domperidone is a dopamine-receptor blocking agent. Its action on the dopamine-receptors in the chemo-emetictrigger zone produces an anti-emetic effect.

Domperidone does not cross the blood-brain barrier to any appreciable degree and so exerts relatively little effect on

cerebral dopaminergic receptors.

Domperidone has been shown to increase the duration of antral and duodenal contractions, to increase the gastric

emptying.

Domperidone does not alter gastric secretions and has no effect on intracranial pressure or on the cardiovascular

system.

Domperidone is rapidly absorbed, with peak plasma concentrations approximately 1 hour after oral administration.

The absolute bio-availability of oral domperidone is low (approximately 15%) due to first-pass hepatic and intestinal

metabolism.

Domperidone is 91 - 93% bound to plasma proteins. The plasma half-life after a single oral dose is 7 - 9 hours in

healthy subjects but is prolonged in patients with severe renal insufficiency.

Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation. In vitro

metabolism experiments with diagnostic inhibitors revealed that CYP3A4 is a major form of cytochrome P-450

involved in the N-dealkylation of domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 are involved in

domperidone aromatic hydroxylation. Urinary and faecal excretion amount to 31% and 66% of the oral dose,

respectively. The proportion of drug, excreted unchanged is small (approximately 1% of urinary and 10% of faecal

excretion).

INDICATIONS

MOTILIUM is indicated for:-Delayed gastric emptying of functional origin with gastro-oesophageal reflux and/or dyspepsia.


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-Control of nausea and vomiting of central or local origin.

-As an anti-emetic in patients receiving cytostatic and radiation therapy.

-Facilitates radiological examination of the upper gastrointestinal tract.

CONTRA-INDICATIONSMOTILIUM is contra-indicated in patients with known sensitivity to domperidone.

MOTILIUM should not be used whenever stimulation of gastric motility is to be avoided or could be harmful, e.g.

in the presence of gastro-intestinal haemorrhage, obstruction or perforation.

MOTILIUM is also contra-indicated in patients with a prolactin releasing pituitary tumour (prolactinoma).

The safety of use during pregnancy and lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE

Acute conditions (mainly nausea, vomiting, hiccup)

Adults: 20 mg (20 mL of suspension or 4 medicine measures) 3 - 4 times per day, 15 to 30 minutes before meals

and, if necessary, before retiring.

Children: 5 mg (5 mL of suspension or 1 medicine measure) per 10 kg body mass, 3 - 4 times per day, 15 to 30

minutes before meals and, if necessary before retiring.

Chronic conditions (mainly dyspepsia)

Adults: 10 mg (10 mL of suspension or 2 medicine measures) taken 3 times per day, 15 to 30 minutes before meals

and, if necessary, before retiring. The dosage may be doubled.Children: 2,5 mg (2,5 mL suspension or a medicine measure) per 10 kg body mass taken 3 times per day, 15 to

30 minutes before meals and, if necessary before bedtime.

Directions for use

The bottle comes with a child-proof cap, and should be opened as follows: {illustrated} 1.push the plastic screw cap down,

2.while pressing down, turn the cap counter clockwise.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS

Side-effects

Allergic reactions, such as rash or urticaria, have been reported.

Abdominal cramps have been reported.Dystonic reactions (extrapyramidal phenomena) may occur.

Reversible raised serum prolactin levels have been observed which may lead to galactorrhoea and gynaecomastia.

Hypertensive crises in patients with phaeochromocytoma may occur with administration of domperidone.

Where the blood brain barrier is not fully developed (mainly in young babies) or is impaired, the possible occurrence

of neurological side-effects cannot be totally excluded.

Special precautions

MOTILIUM should be used with caution in patients with renal impairment or in those at risk of fluid retention. In

patients with severe renal insufficiency (serum creatinine more than 6 mg/100 mL, i.e. more than 0,6 mmol/L) the

elimination half-life of domperidone was increased from 7,4 to 20,8 hours. The dosing frequency should be reduced

to once or twice daily, depending on the severity of impairment, and the dose may need to be reduced. Patients on

prolonged therapy should be reviewed regularly.

Since domperidone is highly metabolised in the liver, MOTILIUM should be used with caution in patients with

hepatic impairment (and in the elderly).

Interactions

Concomitant administration of anti-cholinergic drugs may inhibit the anti-dyspeptic effects of MOTILIUM.

Anti-muscarinic agents and opioid analgesics may antagonise the effect of MOTILIUM.

MOTILIUM suppresses the peripheral effects (digestive disorders, nausea and vomiting) of dopaminergic agonists.

Since MOTILIUM has gastro-kinetic effects, it could influence the absorption of concomitant orally administered

medicines, particularly those with sustained release or enteric coated formulations.


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As MOTILIUM interferes with serum prolactin levels, it may interfere with other hypoprolactinaemic agents and

with some diagnostic tests.

Antacids and anti-secretory agents lower the oral bioavailability of domperidone. They should be taken after meals

and not before meals, i.e. they should not be taken simultaneously with MOTILIUM.

Reduced gastric acidity impairs the absorption of domperidone. Oral bioavailability is decreased by prior

administration of cimetidine or sodium carbonate.

The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggests that the concomitant use of

drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone. Examples of

CYP3A4 inhibitors include the following:

- azole antifungals

- macrolide antibiotics

- HIV protease inhibitors

- nefazodone.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT

Symptoms of overdosage may include drowsiness, disorientation and extrapyramidal reactions, especially in

children.

Anticholinergic, anti-parkinson medicines or antihistamines with anticholinergic properties may be helpful incontrolling the extrapyramidal reactions. There is no specific antidote to domperidone but in the event of

overdosage, gastric lavage as well as the administration of activated charcoal may be useful. Symptomatic and

supportive measures are recommended.

IDENTIFICATION

White suspension with a sweet taste.

PRESENTATION

100 mL or 200 mL amber glass bottles.

STORAGE INSTRUCTIONS

Store below 25C. Protect from light.

KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER

V/5.7.2/19

NAME AND BUSINESS ADDRESS OF THE APPLICANT

JANSSEN-CILAG

JANSSEN PHARMACEUTICA (PTY) LTD

(Reg. No. 80/11122/07)

15th Road

HALFWAY HOUSE1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT

29 April 1993

Code No:023926

2000F

Britepak


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Trademark

Updated on this site: January 2001

Current: May 2005

Source: Pharmaceutical Industry

Compounding alternativesOral liquids are available in some countries; they usually contain sorbitol,microcrystalline cellulose, sodium carboxymethylcellulose, methyl p-hydroxybenzoate,propyl p-hydroxybenzoate, sodium saccharin, polysorbate 20 , sodium hydroxide, andpurified water. Some tablet formulations disperse easily.FormulationsA New Zealand standardised formulation is availableFormula and BatchSheetThis formula uses Ora-Blend/SF or Ora-Plus and Ora-Sweet/SF; 1:1. Alternatives are

given below.

Domperidone suspensions of both 1 and 10 mg/mL in a 1:1 mixture of Ora-Sweet andOra-Plus were reported to be physically and chemically stable for a period of up to 91days, both at room temperature and under refrigeration. The pH of the suspensionsranged from about 4.3 - 4.6 (1)

The formula suggested below is a possible alternative If the commercial base is notavailable. Add citric acid to ensure the pH is in the range quoted above and assign amore conservative expiration date (30 days suggested).

Formula

Domperidone Suspension 1mg per mL

Domperidone tablets 10mg 10Glycerol 20 mLMethylcellulose 1% 50 mLParabens 0.1 %

Water to 100 mLExpiry: 30 days.Storage: Refrigerate. Protect from light.Shake well before use
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References

1. Ensom, Mary H.H., Decarie, Diane., Hamilton, Don P. Stability of Domperidone in ExtemporaneouslyCompounded Suspensions. Journal of Informed Pharmacotherapy 2002;8 (Jan-Mar)

DOMPERIDON

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