CONTRAINDICATIONS
Metoclopramide should not be used whenever stimulation of gastrointestinal motility
might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical
obstruction, or perforation).
Metoclopramide is contraindicated in patients with pheochromocytoma because the drug
may cause a hypertensive crisis, probably due to release of catecholamines from the
tumor. Such hypertensive crises may be controlled by phentolamine.
Metoclopramide is contraindicated in patients with known sensitivity or intolerance to the
drug.
Metoclopramide should not be used in epileptics or patients receiving other drugs which
are likely to cause extrapyramidal reactions, since the frequency and severity of seizures
or extrapyramidal reactions may be increased.
WARNINGS
Mental depression has occurred in patients with and without prior history of depression.
Symptoms have ranged from mild to severe and have included suicidal ideation and
suicide. Metoclopramide should be given to patients with a prior history of depression
only if the expected benefits outweigh the potential risks.
Extrapyramidal symptoms, manifested primarily as acute dystonic reactions, occur in
approximately 1 in 500 patients treated with the usual adult dosages of 30-40 mg/day of
metoclopramide. These usually are seen during the first 24-48 hours of treatment with
metoclopramide, occur more frequently in children and young adults, and are even more
frequent at the higher doses. These symptoms may include involuntary movements of
limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue,
bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic
reactions may present as stridor and dyspnea, possibly due to laryngospasm. If these
symptoms should occur, 50 mg of diphenhydramine HCl (Benadryl) injection should be
given intramuscularly, and they usually will subside. Benztropine mesylate (Cogentin)
injection, 1-2 mg intramuscularly, may also be used to reverse these reactions.
Parkinsonian-like symptoms have occurred, more commonly within the first 6 months
after beginning treatment with metoclopramide, but occasionally after longer periods.
These symptoms generally subside within 2-3 months following discontinuance of
metoclopramide. Patients with preexisting Parkinson's disease should be given
metoclopramide cautiously, if at all, since such patients may experience exacerbation of
parkinsonian symptoms when taking metoclopramide.
Tardive Dyskinesia: Tardive dyskinesia, a syndrome consisting of potentially
irreversible, involuntary, dyskinetic movements may develop in patients treated with
metoclopramide. Although the prevalence of the syndrome appears to be highest among
the elderly, especially elderly women, it is impossible to predict which patients are likely
to develop the syndrome. Both the risk of developing the syndrome and the likelihood
that it will become irreversible are believed to increase with the duration of treatment and
the total cumulative dose.
Less commonly, the syndrome can develop after relatively brief treatment periods at low
doses; in these cases, symptoms appear more likely to be reversible.
There is no known treatment for established cases of tardive dyskinesia although the
syndrome may remit, partially or completely, within several weeks-to-months after
metoclopramide is withdrawn. Metoclopramide itself, however, may suppress (or
partially suppress) the signs of tardive dyskinesia, thereby masking the underlying disease
process. The effect of this symptomatic suppression upon the long-term course of the
syndrome is unknown. Therefore, the use of metoclopramide for the symptomatic control
of tardive dyskinesia is not recommended.
PRECAUTIONS
General
In one study in hypertensive patients, intravenously administered metoclopramide was
shown to release catecholamines; hence, caution should be exercised when
metoclopramide is used in patients with hypertension.
Additional Information for Injection: 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.
Intravenous administration of metoclopramide HCl injectable diluted in a parenteral
solution should be made slowly over a period of not less than 15 minutes.
Giving a promotility drug such as metoclopramide theoretically could put increased
pressure on suture lines following a gut anastomosis or closure. Although adverse events
related to this possibility have not been reported to date, the possibility should be
considered and weighed when deciding whether to use metoclopramide or nasogastric
suction in the prevention of postoperative nausea and vomiting.
Information for the Patient
Metoclopramide may impair the mental and/or physical abilities required for the
performance of hazardous tasks such as operating machinery or driving a motor vehicle.
The ambulatory patient should be cautioned accordingly.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
A 77-week study was conducted in rats with oral doses up to about 40 times the
maximum recommended human daily dose. Metoclopramide elevates prolactin levels and
the elevation persists during chronic administration. Tissue culture experiments indicate
that approximately one-third of human breast cancers are prolactin-dependent in vitro, a
factor of potential importance if the prescription of metoclopramide is contemplated in a
patient with previously detected breast cancer. Although disturbances such as
galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with
prolactin-elevating drugs, the clinical significance of elevated serum prolactin levels is
unknown for most patients. An increase in mammary neoplasms has been found in
rodents after chronic administration of prolactin-stimulating neuroleptic drugs and
metoclopramide. Neither clinical studies nor epidemiologic studies conducted to date,
however, have shown an association between chronic administration of these drugs and
mammary tumorigenesis; the available evidence is too limited to be conclusive at this time.
An Ames mutagenicity test performed on metoclopramide was negative.
Pregnancy, Teratogenic Effects, Pregnancy Category B
Reproduction studies performed in rats, mice, and rabbits by the IV, IM, SC and oral
routes at maximum levels ranging from 12 to 250 times the human dose have
demonstrated no impairment of fertility or significant harm to the fetus due to
metoclopramide. There are, however, no adequate and well-controlled studies in
pregnant women. Because animal reproduction studies are not always predictive of
human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
Metoclopramide is excreted in human milk. Caution should be exercised when
metoclopramide is administered to a nursing mother.
Pediatric Use
There are insufficient data to support efficacy or make dosage recommendations for
metoclopramide in patients less than 18 years of age; therefore, such use is not
recommended (see OVERDOSAGE).