DOMPERIDON

NAMA GENERIK
Domperidon
NAMA KIMIA
5-Chloro-l-{l-[3-(2-oxobenzimidazolin-l-yl)propyl]-4-piperidyl}benzimidazolin-2-one.
STRUKTUR KIMIA
C22H24ClN5O2
SIFAT FISIKOKIMIA
Serbuk warna putih atau hampir putih, polimorfisa. Praktis tidak larut dalam air, sedikit larut
dalam alkohol dan metanol, larut dalam dimetilforfamide.
SUB KELAS TERAPI
Obat Untuk Saluran Cerna
FARMAKOLOGI
Absorpsi (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. Per
rektal : 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 PENYIMPANAN
Simpan dalam wadah terlindung dari cahaya.
KONTRA INDIKASI
Prolaktinoma, gangguan hati, dimana peningkatan motilitas gastro-intestinal dapat
berbahaya;Hipersensitif terhadap Domperidon.
EFEK SAMPING
Gangguan gastrointestinal termasuk kram (jarang), efek ekstrapiramidal (sangat jarang), dan
kemerahan pada kulit.;Hiperprolaktinemia / terjadi peningkatan konsentrasi prolaktin plasma,
yang menyebabkan galactorrhoea atau gynaecomastia.
INTERAKSI OBAT
Analgesik opioid dan antimuskarinik memberikan efek antagonis terhadap efek prokinetik dari
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 pada
Domperidon 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 sebelumnya
diberikan Cimetidine 300 mg atau larutan Sodium bikarbonat.Domperidon merupakan antagonis
efek hipoprolaktinemia dari Bromkokriptin.
PENGARUH HASIL LAB
Meningkatkan serum Thyroid Stimulating Hormone.
PENGARUH KEHAMILAN
Kategori 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 penggunaannya
selama kehamilan.
PENGARUH MENYUSUI
Sejumlah kecil Domperidon diekskresikan melalui ASI, tetapi dilaporkan tidak ada efek samping
pada bayi. Domperidon telah digunakan untuk menstimulasi produksi ASI karena kerjanya
meningkatkan 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 SEDIAAN
Tablet/Film Coated Tablet 10 mg, Suspensi 5 mg / 5 ml, Sirup 5 mg / 5 ml, Oral drops 5 mg/ml
PERINGATAN
Penyesuaian dosis diperlukan pada pasien yang mendapat Domperidon bersama dengan
Simetidine;Tidak dianjurkan untuk pemakaian jangka panjang atau pencegahan rutin mual-
muntah pasca operasi.
MEKANISME AKSI
Domperidon 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.;Domperidon
merangsang motilitas saluran cerna bagian atas tanpa mempengaruhi sekresi gastrik, empedu dan
pankreas. Peristaltik lambung meningkat sehingga dapat mempercepat pengosongan lambung
Domperidone: Obat Antiemetika (Antimuntah)

Nama Dagang: DOM (Lapi), Dombaz (Zenith Pharma), Domedon (Tempo Scan
Pacific), 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/ml
Gliserin 20 ml
Metilselulosa 50 ml
Paraben 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 antagonis
dopamine derivate benzimidazol yang mempunyai potensi sebagai antiemetika karena
adanya kombinasi efek perifer (sebagai gastrokinetik) dan antagonis reseptor dopamine
pada chemoreceptor trigger zone yang terletak di luar sawar darah otak.

Farmakodinamik: Domperidone memperlama kontraksi antro-duodenal, mempercepat
pengosongan 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
Purified water.
Excipients with known effect:
Sorbitol 2.275g/5ml
Methyl hydroxybenzoate 9.000mg/5ml
Propyl hydroxybenzoate 1.000mg/5ml

MOTILIUM 1 mg/mL suspension.

SCHEDULING STATUS
Schedule 2.

PROPRIETARY NAME
(and dosage form)

MOTILIUM

1 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-emetic
trigger 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.
- 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-INDICATIONS
MOTILIUM 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.
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 in
controlling 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 HOUSE
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT
29 April 1993

Code No:023926
2000F
Britepak

Trademark

Updated on this site: January 2001
Current: May 2005
Source: Pharmaceutical Industry

Compounding alternatives
Oral 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, and
purified water. Some tablet formulations disperse easily.
FormulationsA New Zealand standardised formulation is available Formula and Batch
Sheet
This 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 and
Ora-Plus were reported to be physically and chemically stable for a period of up to 91
days, both at room temperature and under refrigeration. The pH of the suspensions
ranged from about 4.3 - 4.6 (1)

The formula suggested below is a possible alternative If the commercial base is not
available. Add citric acid to ensure the pH is in the range quoted above and assign a
more conservative expiration date (30 days suggested).

Formula

Domperidone Suspension 1mg per mL

Domperidone tablets 10mg 10
Glycerol 20 mL
Methylcellulose 1% 50 mL
Parabens 0.1 %
Water to 100 mL
Expiry: 30 days.
Storage: Refrigerate. Protect from light.
Shake well before use




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