Domperidone Tablets 10 mg is indicated for relief of the symptoms of nausea and
vomiting.

Nausidom tablets 10 mg should be used at the lowest effective dose for the
shortest duration necessary to control nausea and vomiting.
It is recommended to take oral Domperidone Tablets 10 mg before meals. If
taken after meals, absorption of the drug is somewhat delayed.
Patients should try to take each dose at the scheduled time. If a scheduled dose
is missed, the missed dose should be omitted and the usual dosing schedule
resumed. The dose should not be doubled to make up for a missed dose.
Usually, the maximum treatment duration should not exceed one week.
Adults and adolescents (12 years of age and older and weighing 35 kg or
more)
One 10mg tablet up to three times per day with a maximum dose of 30 mg per
day.
Neonates, infants, children (less than 12 years of age) and adolescents weighing
less than 35 kg.

Due to the need for accurate dosing, Domperidone Tablets 10 mg are unsuitable
for use in children and adolescents weighing less than 35 kg.
Hepatic Impairment
Domperidone Tablets 10 mg is contraindicated in moderate or severe hepatic
impairment. Dose modification in mild hepatic impairment is however not needed.
Renal Impairment
Since the elimination half-life of domperidone is prolonged in severe renal
impairment, on repeated administration, the dosing frequency of Domperidone
Tablets 10 mg should be reduced to once or twice daily depending on the severity
of the impairment, and the dose may need to be reduced. Such patients on
prolonged therapy should be reviewed regularly.

Domperidone Tablets 10 mg is contraindicated in the following situations: • Known hypersensitivity to domperidone or any of the excipients • Prolactin-releasing pituitary tumour (prolactinoma). • when stimulation of the gastric motility could be harmful e.g in patients with gastro-intestinal haemorrhage, mechanical obstruction or perforation. • in patients with moderate or severe hepatic impairment. • in patients who have known existing prolongation of cardiac conduction intervals, particularly QTc, patients with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure. • co-administration with QT-prolonging drugs. • co-administration with potent CYP3A4 inhibitors (regardless of their QT prolonging effects)

Cardiovascular effects
Domperidone has been associated with prolongation of the QT interval on the
electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointes in patients taking domperidone.
These reports included patients with confounding risk factors, electrolyte
abnormalities and concomitant treatment which may have been contributing
factors.
Epidemiological studies showed that domperidone was associated with an
increased risk of serious ventricular arrhythmias or sudden cardiac death. A
higher risk was observed in patients older than 60 years, patients taking daily
doses greater than 30 mg, and patients concurrently taking QT-prolonging drugs
or CYP3A4 inhibitors.
Domperidone should be used at the lowest effective dose in adults and children.
Domperidone is contraindicated in patients with known existing prolongation of
cardiac conduction intervals, particularly QTc, in patients with significant
electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia), or
bradycardia, or in patients with underlying cardiac diseases such as congestive
heart failure due to increased risk of ventricular arrhythmia. Electrolyte
disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) or bradycardia
are known to be conditions increasing the proarrythmic risk.
Treatment with domperidone should be stopped if signs or symptoms occur that
may be associated with cardiac arrhythmia, and the patients should consult their
physician.
Patients should be advised to promptly report any cardiac symptoms.
Use in infants
Although neurological side effects are rare, the risk of neurological side effects is
higher in young children since metabolic functions and the blood-brain barrier are
not fully developed in the first months of life. Overdosing may cause
extrapyramidal symptoms in children, but other causes should be taken into
consideration.
Renal impairment
The elimination half-life of domperidone is prolonged in severe renal impairment.
For repeated administration, the dosing frequency of Domperidone Tablets 10 mg
should be reduced to once or twice daily depending on the severity of the
impairment. The dose may also need to be reduced.

Excipients
The film-coated tablets contain lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicine.

The main metabolic pathway of domperidone is through CYP3A4. In vitro data
suggest that the concomitant use of drugs that significantly inhibit this enzyme
may result in increased plasma levels of domperidone.
Increased risk of occurrence of QT-interval prolongation, due to
pharmacodynamic and/or pharmacokinetic interactions.
Concomitant use of the following substances is contraindicated
QTc prolonging medicinal products
• anti-arrhythmics class IA (e.g., disopyramide, hydroquinidine, quinidine)
• anti-arrhythmics class III (e.g., amiodarone, dofetilide, dronedarone, ibutilide,
sotalol)
• certain anti-psychotics (e.g., haloperidol, pimozide, sertindole)
• certain anti-depressants (e.g., citalopram, escitalopram)
• certain antibiotics (e.g. , erythromycin, levofloxacin, moxifloxacin, spiramycin)
• certain antifungal agents (e.g., pentamidine)
• certain antimalarial agents (in particular halofantrine, lumefantrine)
• certain gastro-intestinal medicines (e.g., cisapride, dolasetron, prucalopride)
• certain antihistaminics (e.g., mequitazine, mizolastine)
• certain medicines used in cancer (e.g., toremifene, vandetanib, vincamine)
• certain other medicines (e.g., bepridil, diphemanil, methadone).
• Potent CYP3A4 inhibitors (regardless of their QT prolonging effects), i.e.:
• protease inhibitors
• systemic azole antifungals
• some macrolides (erythromycin, clarithromycin, telithromycin)
Concomitant use of the following substances is not recommended
Moderate CYP3A4 inhibitors i.e. diltiazem, verapamil and some macrolides.

Concomitant use of the following substances requires caution in use
Caution with bradycardia and hypokalaemia-inducing drugs, as well as with the
following macrolides involved in QT-interval prolongation: azithromycin and
roxithromycin (clarithromycin is contra-indicated as it is a potent CYP3A4
inhibitor).
The above list of substances is representative and not exhaustive.
Separate in vivo pharmacokinetic/pharmacodynamic interaction studies with oral
ketoconazole or oral erythromycin in healthy subjects confirmed a marked
inhibition of domperidone's CYP3A4 mediated first pass metabolism by these
drugs.
With the combination of oral domperidone 10mg four times daily and
ketoconazole 200mg twice daily, a mean QTc prolongation of 9.8 msec was seen
over the observation period, with changes at individual time points ranging from
1.2 to 17.5 msec. With the combination of domperidone 10mg four times daily
and oral erythromycin 500mg three times daily, mean QTc over the observation
period was prolonged by 9.9 msec, with changes at individual time points ranging
from 1.6 to 14.3 msec. Both the Cmax and AUC of domperidone at steady state
were increased approximately three-fold in each of these interaction studies. In
these studies domperidone monotherapy at 10mg given orally four times daily
resulted in increases in mean QTc of 1.6msec (ketoconazole study) and 2.5msec
(erythromycin study), while ketoconazole monotherapy (200mg twice daily) led
to increases in QTc of 3.8 and 4.9 msec, respectively, over the observation
period.

Pregnancy
There are limited post-marketing data on the use of domperidone in pregnant
women. Studies in animals have shown reproductive toxicity at maternally toxic
doses. Domperidone Tablets 10 mg should only be used during pregnancy when
justified by the anticipated therapeutic benefit.

Breast-feeding
Domperidone is excreted in human milk and breast-fed infants receive less than
0.1 % of the maternal weight-adjusted dose. Occurrence of adverse effects, in
particular cardiac effects cannot be excluded after exposure via breast milk. A
decision should be made whether to discontinue breast-feeding or to
discontinue/abstain from domperidone therapy taking into account the benefit of
breast feeding for the child and the benefit of therapy for the woman. Caution
should be exercised in case of QTc prolongation risk factors in breast-fed infants.

Domperidone Tablets 10 mg has no or negligible influence on the ability to drive
and use machines.

Tabulated list of adverse reactions
The safety of Domperidone Tablets 10 mg was evaluated in clinical trials and in
postmarketing experience. The clinical trials included 1275 patients with
dyspepsia, gastro-oesophageal reflux disorder (GORD), Irritable Bowel Syndrome
(IBS), nausea and vomiting or other related conditions in 31 double-blind,
placebo-controlled studies. All patients were at least 15 years old and received at
least one dose of Domperidone Tablets 10 mg (domperidone base). The median
total daily dose was 30 mg (range 10 to 80 mg), and median duration of
exposure was 28 days (range 1 to 28 days). Studies in diabetic gastroparesis or
symptoms secondary to chemotherapy or parkinsonism were excluded.
The following terms and frequencies are applied:
very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to
<1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), Where
frequency can not be estimated from clinical trials data, it is recorded as “Not
known”.

SYSTEM ORGAN
CLASS
ADVERSE DRUG REACTION FREQUENCY
COMMON UNCOMMON NOT KNOWN
Immune system
disorders
Anaphylactic reaction
(including
anaphylactic shock)
Psychiatric disorders Loss of libido
Anxiety
Agitation
Nervousness
Nervous system
disorders
Somnolence
Headache
Convulsion
Extrapyramidal
disorder
Eye disorders Oculogyric crisis
Cardiac disorders Ventricular
arrhythmias
Sudden cardiac death
QTc prolongation
Torsade de Pointes
Gastrointestinal
disorders
Dry mouth Diarrhoea
Skin and
subcutaneous tissue
disorder
Rash
Pruritus
Urticaria
Angioedema
Renal and urinary
disorders
Urinary retention
Reproductive system
and breast disorders
Galactorrhoea
Breast pain
Breast tenderness
Gynaecomastia
Amenorrhoea
General disorders and
administration site
conditions
Asthenia
Investigations Liver function test
abnormal
Blood prolactin
increased.

In 45 studies where domperidone was used at higher dosages, for longer duration and for
additional indications including diabetic gastroparesis, the frequency of adverse events (apart
from dry mouth) was considerably higher. This was particularly evident for pharmacologically
predictable events related to increased prolactin. In addition to the reactions listed above,
akathisia, breast discharge, breast enlargement, breast swelling, depression,
hypersensitivity, lactation disorder, and irregular menstruation were also noted.

Paediatric population
Extrapyramidal disorder occurs primarily in neonates and infants
Other central nervous system-related effects of convulsion and agitation also are
primarily reported in infants and children.
To report any side effect(s):
 Saudi Arabia:
 The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662
o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc
 Other GCCStates:
Please contact the relevant competent authority.

Symptoms
Overdose has been reported primarily in infants and children. Symptoms of
overdosage may include agitation, altered consciousness,
convulsions,disorientation, somnolence and extrapyramidal reactions.
Treatment
There is no specific antidote to domperidone, but in the event of overdose,
standard symptomatic treatment should be given immediately. Gastric lavage as
well as the administration of activated charcoal, may be useful. ECG monitoring
should be undertaken, because of the possibility of QT interval prolongation.
Close medical supervision and supportive therapy is recommended.
Anticholinergic, anti-parkinson drugs may be helpful in controlling the
extrapyramidal reactions.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic Properties
Pharmacotherapeutic Group : Propulsives
ATC Code: A03FA03
Mechanism of action
Domperidone is a dopamine antagonist with anti-emetic properties, Domperidone
does not readily cross the blood-brain barrier. In domperidone users, especially in
adults, extrapyramidal side effects are very rare, but domperidone promotes the
release of prolactin from the pituitary. Its anti-emetic effect may be due to a
combination of peripheral (gastrokinetic) effects and antagonism of dopamine
receptors in the chemoreceptor trigger zone, which lies outside the blood-brain
barrier in the area postrema. Animal studies, together with the low
concentrations found in the brain, indicate a predominantly peripheral effect of
domperidone on dopamine receptors.
Studies in man have shown oral domperidone to increase lower oesophaegeal
pressure, improve antroduodenal motility and accelerate gastric emptying. There
is no effect on gastric secretion.
In accordance with ICH—E14 guidelines, a thorough QT study was performed.
This study included a placebo, an active comparator and a positive control and
was conducted in healthy subjects with up to 80 mg per day 10 or 20 mg
administered 4 times a day of domperidone. This study found a maximal
difference of QTc between domperidone and placebo in LS-means in the change
from baseline of 3.4 msec for 20 mg domperidone administered 4 times a day on
Day 4. The 2-sided 90 % CI (1.0 to 5.9 msec) did not exceed 10 msec. No
clinically relevant QTc effects were observed in this study when domperidone was
administered at up to 80 mg/day (i.e., more than twice the maximum
recommended dosing).
However, two previous drug-drug interaction studies showed some evidence of
QTc prolongation when domperidone was administered as monotherapy (10 mg 4
times a day).The largest time-matched mean difference of QTcF between
domperidone and placebo was 5.4 msec (95 % CI: -1.7 to 12.4) and 7.5 msec
(95 % CI: 0.6 to 14.4), respectively.

Absorption
Domperidone is rapidly absorbed after oral administration, with peak plasma
concentrations occurring at approximately 1hr after dosing. The Cmax and AUC
values of domperidone increased proportionally with dose in the 10 mg to 20 mg
dose range. A 2- to 3-fold accumulation of domperidone AUC was observed with
repeated four times daily (every 5 hr) dosing of domperidone for 4 days.
The low absolute bioavailability of oral domperidone (approximately 15%) is due
to an extensive first-pass metabolism in the gut wall and liver. Although
domperidone's bioavailability is enhanced in normal subjects when taken after a
meal, patients with gastro-intestinal complaints should take domperidone 15-30
minutes before a meal. Reduced gastric acidity impairs the absorption of
domperidone.
Oral bioavailability is decreased by prior concomitant administration of cimetidine
and sodium bicarbonate. The time of peak absorption is slightly delayed and the
AUC somewhat increased when the oral drug is taken after a meal.
Distribution
Oral domperidone does not appear to accumulate or induce its own metabolism;
a peak plasma level after 90 minutes of 21 ng/ml after two weeks oral
administration of 30 mg per day was almost the same as that of 18 ng/ml after
the first dose. Domperidone is 91-93% bound to plasma proteins. Distribution
studies with radiolabelled drug in animals have shown wide tissue distribution,
but low brain concentration. Small amounts of drug cross the placenta in rats.
Metabolism
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.
Excretion
Urinary and faecal excretions amount to 31 and 66% of the oral dose
respectively. The proportion of the drug excreted unchanged is small (10% of
faecal excretion and approximately 1% of urinary excretion). 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.
Hepatic impairment
In subjects with moderate hepatic impairment (Pugh score 7 to 9, Child-Pugh
rating B), the AUC and Cmax of domperidone is 2.9- and 1.5-fold higher,
respectively, than in healthy subjects. The unbound fraction is increased by 25%,
and the terminal elimination half-life is prolonged from 15 to 23 hours. Subjects
with mild hepatic impairment have a somewhat lower systemic exposure than
healthy subjects based on Cmax and AUC, with no change in protein binding or
terminal half-life. Subjects with severe hepatic impairment were not studied.
Domperidone Tablets 10 mg is contraindicated in patients with moderate or
severe hepatic impairment.
Renal impairment
In subjects with severe renal insufficiency (creatinine clearance
<30ml/min/1.73m2) the elimination half-life of domperidone is increased from 7.4
to 20.8 hours, but plasma drug levels are lower than in healthy volunteers. Since
very little unchanged drug (approximately 1%) is excreted via the kidneys, it is
unlikely that the dose of a single administration needs to be adjusted in patients
with renal insufficiency.
However, on repeated administration, the dosing frequency should be reduced to
once or twice daily depending on the severity of the impairment, and the dose
may need to be reduced.
Paediatric population
No pharmacokinetic data are available in the paediatric population.

Electrophysiological in vitro and in vivo studies indicate an overall moderate risk
of domperidone to prolong the QT interval in humans. In in vitro experiments on
isolated cells transfected with hERG and on isolated guinea pig myocytes,
exposure ratios ranged between 26- 47-fold, based on IC50 values inhibiting
currents through IKr ion channels in comparison to the free plasma
concentrations in humans after administration of the maximum daily dose of 10
mg administered 3 times a day. Safety margins for prolongation of action
potential duration in in vitro experiments on isolated cardiac tissues exceeded the free plasma concentrations in humans at maximum daily dose (10 mg
administered 3 times a day) by 45-fold. Safety margins in in vitro pro-arrhythmic
models (isolated Langendorff perfused heart) exceeded the free plasma
concentrations in humans at maximum daily dose (10 mg administered 3 times a
day) by 9- up to 45-fold. In in vivo models the no effect levels for QTc
prolongation in dogs and induction of arrhythmias in a rabbit model sensitized for
torsade de pointes exceeded the free plasma concentrations in humans at
maximum daily dose (10 mg administered 3 times a day) by more than 22-fold
and 435-fold, respectively. In the anesthetized guinea pig model following slow
intravenous infusions, there were no effects on QTc at total plasma
concentrations of 45.4 ng/mL, which are 3-fold higher than the total plasma
levels in humans at maximum daily dose (10 mg administered 3 times a day).
The relevance of the latter study for humans following exposure to orally
administered domperidone is uncertain.
In the presence of inhibition of the metabolism via CYP3A4 free plasma
concentrations of domperidone can rise up to 3-fold.
At a high, maternally toxic dose (more than 40 times the recommended human
dose), teratogenic effects were seen in the rat. No teratogenicity was observed in
mice and rabbits.

S. NO. MATERIAL FUNCTION
CORE EXCIPIENTS
1. Lactose (200 mesh)Ph.Eur. Diluent
2. Maize Starch Ph.Eur. Diluent
3. Sodium Lauryl Sulphate BP Surfactant
4. Povidone (K-29/32) BP Binder
5. Purified Water USP Granulating Agent
6. Microcrystalline Cellulose (Grade 102)
BP/Ph.Eur.
Diluent
7. Colloidal Anhydrous Silica BP/Ph.Eur. Glidant
8. Magnesium Stearate Ph.Eur. Lubricant
9. Opadry White Y-1-7000 Coating Agent
PRODUCT NAUSIDOM TABLETS 10 mg
REGISTRATION FILE – MODULE 1

Not Applicable

24 Months

Store below 30°C.

The tablets are packed in Alu/PVC-PVDC blisters and placed in a printed carton
along with the pack insert.
Pack size: 30’s.

Not Applicable