Monograph: |
Domperidone
Domperidone (Ph. Eur.) is a white or almost white powder.
Practically insoluble in water, slightly soluble in alcohol and
methyl alcohol: soluble in dimethylformamide. Protect from
light.
Domperidone Maleate (Ph. Eur.) is a white or almost white
powder; its exhibits polymorphism. Very slightly soluble in
water and in alcohol: sparingly soluble in dimethylforma-
mide; slightly soluble in methyl alcohol. Protect from light.
Adverse Effects
Domperidone does not readily cross the blood-brain
barrier and the incidence of central effects such as
extrapyramidal reactions or drowsiness may be low-
er than with metoclopramide; however,
there have been reports of dystonic reactions. Plas-
ma-prolactin concentrations may also be increased
which may lead to galactorrhoea or gynaecomastia.
Domperidone by injection has been associated with
convulsions, arrhythmias, and cardiac arrest. Fatali-
ties have restricted administration by this route.
Effects on the cardiovascular system. Sudden death has
occurred in cancer patients given domperidone intravenously
in high doses. Four cancer patients experienced cardiac ar-
rest following high intravenous doses and 2 of 4 similar pa-
tients experienced ventricular arrhythmias. Following such
reports the manufacturers withdrew the injection from gener-
al use in the UK.
Effects on the endocrine system. Reports of galactor-
rhoea with gynaecomastia or mastalgia generally associat-
ed with raised serum-prolactin concentrations.
Gynaecomastia without galactorrhoea has also been reported.
Extrapyramidal effects. Reports of extrapyramidal symp-
toms. including acute dystonic reactions, in individual pa-
tients given domperidone.
Precautions
Due to similarities in the mode of action, the precau-
tions described under Metoclopramide Hydrochlo-
ride should be observed.
General
In one study in hypertensive patients, intravenously administered was
shown to release catecholamines; hence, caution should be exercised
when domperidone is used in patients with hypertension.
Intravenous injections of undiluted metoclopramide should be made
slowly allowing 1 to 2 minutes for 10 mg since a transient but intense
feeling of anxiety and restlessness, followed by drowsiness, may occur
with rapid administration.
Domperidone should be used with great caution if given
intravenously, because of the risk of arrhythmias, especial-
ly in patients predisposed to cardiac arrhythmias or
hypokalaemia.
Pharmacokinetics
The systemic bioavailability of domperidone is only
about 15% in fasting subjects given a dose by
mouth, although this is increased when domperi-
done is given after food. The low bioavailability is
thought to be due to first-pass hepatic and intestinal
metabolism. The bioavailability of rectal domperi-
done is similar to that following oral administration,
although peak plasma concentrations are only
achieved after about an hour, compared with 30
minutes after a dose by mouth.
Domperidone is more than 90% bound to plasma
protein, and has a terminal elimination half-life of
about 7.5 hours. It is chiefly cleared from the blood
by extensive metabolism. About 30% of an oral dose
is excreted in urine within 24 hours, almost entirely
as metabolites; the remainder of a dose is excreted
in faeces over several days. about 10% as unchanged
drug. It does not readily cross the blood-brain barri-
er.
Small amounts of domperidone are distributed into
breast milk. reaching concentrations about one-
quarter of those in maternal serum.
References.
Uses and Administration
Domperidone is a dopamine antagonist with actions
and uses similar to those of metoclopramide. It is used as an
antiemetic for the short term treatment of nausea and vomiting of
various aetiologies , including that associated with
cancer therapy, and nausea and vomiting associated
with levodopa or bromocriptine therapy for parkin-
sonism. It is not considered suitable for
chronic nausea, and vomiting, nor for the routine
prophylaxis of postoperative vomiting.
Domperidone is also used for its prokinetic actions
in disorders of gastro-intestinal motility
such as diabetic gastroparesis and has been tried in
other gastro-intestinal disorders.
Domperidone is used as the maleate in tablet prepa-
rations, but doses are expressed in terms of the base.
It is administered in doses of 10 to 20 mg by mouth
or 30 to 60 mg rectally every 4 to 8 hours. In the
treatment of nausea and vomiting in parkinsonian
patients, therapy may be continued for a maximum
of 12 weeks. In children doses of 200 to 400 ng per
kg body-weight may be given by mouth every 4 to 8
hours; approximately 2 to 4 mg per kg daily may be
given rectally.
Domperidone has been administered parenterally,
but such administration has been associated with se-
vere adverse effects (see above).
Parkinsonism : Domperidone is used to control gastro-intes-
tinal effects of dopaminergic drugs in the management of par-
kinsonism . It may be of use in those patients who
experience peripheral effects with levodopa despite the use of
peripheral decarboxylase inhibitors and for patients using
dopamine agonists such as bromocriptine or apomorphine
since peripheral decarboxylase inhibitors are ineffective for
preventing the peripheral effects of these drugs. Although
domperidone does not readily cross the blood brain barrier
there have been isolated reports of extrapyramidal effects as-
sociated with its use (see above). Consequently there has been
concern over its potential to produce central effects and some
consider that domperidone should only be used in patients
with parkinsonism when safer antiemetic measures have
failed , However this view has been contested both by the
manufacturers and other workers. In a subsequent review of
the use of domperidone in Parkinson's disease Parkes con-
sidered that domperidone might produce central blockade of
the therapeutic effects of levodopa if given at a high oral dos-
age such as 120 mg daily for prolonged periods but also noted
that such high doses were rarely required to control levodopa-
induced vomiting. In the UK. domperidone is limited to a
maximum of 12 weeks treatment in nausea and vomiting in-
duced by antiparkinsonian treatment.
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