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906 Equine
Compendium October 2001
PHARM PROFILE
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DOMPERIDONE
Amy Renee Parker, PharmD
Campbell University
Buies Creek, North Carolina
T
he dopamine antagonist
domperidone is labeled as an
investigational drug used to
treat fescue toxicosis in horses.1 Fescue toxicosis, which is caused by a
fungus that infects fescue grass pastures, results in severe reproductive
problems, difficulty giving birth, and
lack of milk production.2 Domperidone may regulate the motility of
gastric and small intestinal smooth
muscles, in horses and may, therefore,
have some effect on esophageal
motility in dogs and cats.3 The drug
also has antiemetic activity from
dopaminergic blockage in the
chemoreceptor trigger zone.3 It is approved in Europe for the treatment
of nausea, vomiting, and dyspepsia
in humans.4
PHARMACOLOGY
Domperidone is a peripherally acting dopamine2-receptor antagonist
that blocks the prolactin-depressing
effects of individual ergot alkaloids
in horses. An ergot alkaloid from
fungus-infested fescue causes excess
dopamine production. Excess
dopamine inhibits prolactin production, which is essential to the final
stages of pregnancy and birth. Without the prolactin signal, mares do
not foal at their expected date of parturition.5
Domperidone also acts as a dopamine2-receptor in the gastrointestinal
(GI) tract and at the chemoreceptor
trigger zone in small animals. 6
Domperidone has prokinetic and
antiemetic properties similar to
those of metoclopramide.6 Domperidone appears to have a maximal prokinetic effect in the GI tract. The
drug is effective for treating such
conditions as gastroparesis and gastroesophageal reflux but appears to
have little physiologic effect on the
colon or in colonic motility disorders. 7 Domperidone has not yet
been approved for use in the United
States, and there is little clinical experience with the drug in regard to
companion animals.6 As a prokinetic
agent, domperidone appears to be
more effective in small animals in
improving clinical signs (e.g.,
anorexia, vomiting) associated with
delayed gastric emptying.6
Domperidone is rapidly absorbed
following oral administration.4,8 Although the drug is almost completely
absorbed from the GI tract, oral
bioavailability in humans is only
about 13% to 17% because of extensive first-pass and gut-wall metabolism.4,8 Domperidone is 91% to 93%
bound to plasma proteins, and the
plasma half-life is 7 to 9 hours after
administration of a single oral dose
in humans.4,8 Domperidone undergoes rapid and extensive hepatic me-
tabolism by hydroxylation and Ndealkylation in humans.4,8 The drug
also elevates serum prolactin levels in
humans.4 Pharmacodynamic parameters are currently unavailable for animal species.
INDICATIONS
In humans, domperidone is indicated for delayed gastric emptying of
functional origin with gastroesophageal reflux and/or dyspepsia, control
of nausea and vomiting of central or
local origin, and as an antiemetic in
patients receiving cytostatic and radiation therapy.4 The drug also facilitates radiologic examination of the
upper GI tract.4
In animals, domperidone is currently approved as an investigational drug
for the prevention and treatment of
fescue toxicosis and related agalactia
in periparturient mares.9 Domperidone is used extralabel in small animals to stimulate antral contractions
and enhance gastric emptying. 10–12
Data supporting the use of domperidone in small animals are contradictory because some trials have shown improvement in antral contractions in
dogs but not in cats,10–12 and one trial
showed no enhancement of gastric
emptying in normal dogs.13 No doses
of domperidone were cited in any of
the small animal clinical trials.
CAUTIONS
Because domperidone is a gastric
prokinetic agent, it must not be used
Compendium October 2001
in mares with suspected or confirmed GI blockage. The drug is not
indicated for use in animals intended
for food.9
Adverse Effects
In some cases of long-term domperidone treatment, leakage of milk
and colostrum has occurred. If leakage should occur and foaling does
not take place within 24 hours, half
the recommended dose should be administered twice daily at approximately 12-hour intervals and continued until foaling. If leakage
continues, the dose should be reduced to one third of the recommended dose (still administered twice
daily at 12-hour intervals until foaling). In some cases, treatment may
need to be reduced to very low levels
or discontinued.9
In a trial1 using domperidone for
the treatment of fescue toxicosis in
horses, no central nervous system
side effects were noted. This is most
likely because domperidone does not
cross the blood–brain barrier; therefore, it has less potential for causing
adverse effects, especially on the central nervous system.14
Acute Toxicity
In humans, signs of overdose include drowsiness, disorientation, and
extrapyramidal reactions. Anticholinergic drugs (e.g., atropine) and antihistamines with anticholinergic
properties (e.g., chlorpheniramine,
hydroxyzine, cyproheptadine) may
be helpful in controlling the extrapyramidal reactions. Although
there is no specific antidote to domperidone, in the event of overdose
gastric lavage and activated charcoal
may be helpful. Symptomatic and
supportive measures are recommended.4 No acute toxicity has been reported in animal investigations.
DRUG INTERACTIONS
The use of domperidone in mares
may cause false-positive readings on
Equine 907
milk calcium tests used to predict
foaling.9 Because domperidone interferes with serum prolactin levels, it
may also interfere with other hypoprolactinemic agents. 4 Antacids
and antisecretory agents may lower
the oral bioavailability of domperidone. 4 Oral bioavailability is decreased by prior administration of
cimetidine or sodium carbonate.4 Because domperidone has gastric prokinetic effects, it could influence the
absorption of concomitant orally administered medications, particularly
sustained-release or enteric-coated
formulations.4
DOSAGE AND ADMINISTRATION
Domperidone oral gel should be
administered after fescue toxicosis at
a dosage of 5 ml/500 kg (1100 lb)
mare body weight daily as an oral
dose starting 10 days prior to the expected foaling date and continuing
until foaling. The dose should be adjusted according to the mare’s body
weight. Fescue toxicosis may occur
in mares that are at or past their expected foaling date without signs of
udder development or impending
parturition. Treatment should be initiated immediately and continued
until foaling. On farms with a history of severe fescue toxicosis problems
and where mares will remain on toxic fescue until foaling, the drug may
need to be initiated as early as 15 to
25 days prior to the expected foaling
date and continued until foaling.
Treatment may need to be continued
up to 5 days after foaling in some
mares that are not milking adequately at foaling.9
If used concurrently with domperidone, antacids or antisecretory
agents should be given separately.
Antacids or antisecretory agents
should be administered after meals
because reduced gastric acidity may
impair the absorption of domperidone.4
PREPARATIONS
Equidone ™ (domperidone 11%;
Equi-Tox Pharmaceutical Research
and Development, Pendleton, SC)
oral gel has received investigational
drug status from the FDA. 9 This
product is available as a 25-ml oral
Dial-A-Dose® syringe (Plas-Pak Industries, Norwich, CT), which delivers five doses for an average 1100-lb
mare (Box 1).9 Domperidone tablets
can be imported from Janssen Pharmaceutica (Cilag, United Kingdom)
by obtaining a medically necessary
personal veterinary imports clearance
from the FDA.
Domperidone may be compounded, but it is probably unnecessary
with a gel formulation available.
Redmond and colleagues1 reported a
Box 1. Use of the Dial-A-Dose® Syringe9
• Using the mare’s weight, calculate the appropriate dose (1 ml/220 lb; 5
ml/1100 lb).
• Turn the dial ring on the syringe until the edge of the ring nearest the tip
lines up with the dose to be delivered.
• Make sure the mare’s mouth is free of food or other obstructions.
• Remove the cap, insert the nozzle of the syringe through the interdental
space of the mare’s mouth, and deposit the paste on the back of the
animal’s tongue by depressing the plunger.
• Observe the horse briefly following administration to ensure that the dose
has been ingested.
• Recap the syringe. The remaining contents can be used as part of the next
dose.
908 Equine
Compendium October 2001
Client Counseling Information
• Domperidone is administered to mares for the
prevention and/or treatment of fescue toxicosis,
which can cause spontaneous abortions, prolonged
pregnancy, difficulty giving birth, and lack of milk
production.
• Although domperidone causes few side effects, it
may cause leakage of milk and colostrum. If this
occurs and foaling does not take place within 24
hours, half the recommended dose should be given
q12h. If leakage continues, the dose should be
reduced to one third of the recommended dose
and administered q12h until foaling.
• Dose and duration of therapy may be adjusted as
needed.
• Wash hands thoroughly after administering the
medication.
• Antacids and antisecretory agents should be given
after meals because reduced gastric acidity may
impair the absorption of domperidone.4
• Domperidone should be stored in a dry, cool
environment out of the reach of children and pets.
compounded formulation of domperidone in which a corn
and dried molasses mix was used as the carrier for drug
treatments. Domperidone was dissolved in 5 ml of cider
vinegar and mixed into the grain to facilitate even distribution of the compound.1 An additional 15 ml of cider vinegar was then added to encourage complete consumption of
the ration.1 The mix contained 20% molasses to increase
palatability of the treatments.1
STORAGE AND HANDLING
Domperidone should be kept in a cool, dry place. The
drug should be kept out of reach of children and pets.
REFERENCES
1. Redmond LM, Cross DL, Strickland JR, Kennedy SW: Efficacy
of domperidone and sulpiride as treatments for fescue toxicosis
in horses. Am J Vet Res 55(5):722–729, 1994.
2. The horse interactive—News and notes. Clemson University
discovery delivers healthy mares and foals. Available at: http://
www.thehorse.com/news/index/073099.html; accessed February
12, 2001.
3. Dowling PM: Life after cisapride: Prokinetic drugs for small animals. Vet Med 95(9):678–683, 2000.
4. Package insert: Motilium®. Cilag, United Kingdom, Janssen
Pharmaceutica, 1999.
5. Lawrence LA: Beware of fescue toxicosis in brood mares. Virginia Cooperative Extension. Livestock update. Available at:
http://www.ext.vt.edu/news/periodicals/livestock/aps-97_06/
aps-794.html; updated June 1997.
6. Hall JA, Washabau RJ: Gastric prokinetic agents, in Kirk’s Current Veterinary Therapy XIII: Small Animal Practice. Philadelphia,
WB Saunders Co, 2000, pp 614–617.
7. Longo WE, Vernava AM: Prokinetic agents for lower gastrointestinal motility disorders. Dis Colon Rectum 36(7):696–708,
1993.
8. Barone JA: Domperidone: A peripherally acting dopamine2-receptor antagonist. Ann Pharmacother 33:429–440, 1999.
9. Product information: Equidone™. Pendleton, SC, Equi-Tox,
1999.
10. Mangel AW: Effects of bethanechol, metoclopramide and domperidone on antral contractions in dogs and cats. Digestion
28(4):205–209, 1983.
11. Hess RS, Washburn RJ: Effect of metoclopramide and domperidone on feline gastric smooth muscle. Proc ACVIM :1007, 1995.
12. Schotirkes JA, Van Nueten JM: Control of gastrointestinal coordination: Dopaminergic and cholinergic pathways. Scand J Gastroenterol 92(Suppl):8–12, 1984.
13. Orihata M, Sama SK: Contractile mechanisms of action on gastroprokinetic agents: Cisapride, metoclopramide, and domperidone. Am J Physiol 266(4 Pt 1):G665–G676, 1994.
14. Olin RB, Hebel SK, Connell SI, et al (eds): Drug Facts and
Comparisons. St Louis, Wolters Kluwer, 1991, p 2561.