metoclopramide HCl 10 MG Oral Tablet
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 to 40 mg/day of metoclopramide.
These usually are seen during the first 24 to 48 hours of treatment with metoclopramide, occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at 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, inject 50 mg of diphenhydramine hydrochloride intramuscularly, and they usually will subside.
Benztropine mesylate, 1 to 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 to 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 (see Boxed Warnings ) Treatment with metoclopramide can cause tardive dyskinesia (TD), a potentially irreversible and disfiguring disorder characterized by involuntary movements of the face, tongue, or extremities.
The risk of developing tardive dyskinesia increases with the duration of treatment and the total cumulative dose.
An analysis of utilization of patterns showed that about 20% of patients who used metoclopramide took it longer than 12 weeks.
Treatment with metoclopramide for longer than the recommended 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing TD.
Although the risk of developing TD in the general population may be increased among the elderly, women, and diabetics, it is not possible to predict which patients will develop metoclopramide-induced TD.
Both the risk of developing TD and the likelihood that TD will become irreversible increase with duration of treatment and total cumulative dose.
Metoclopramide should be discontinued in patients who develop signs and symptoms of TD.
There is no known effective treatment for established cases of TD, although in some patients, TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn.
Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process.
The effect of this symptomatic suppression upon the long-term course of TD is unknown.
Therefore, metoclopramide should not be used for the symptomatic control of TD.
Neuroleptic Malignant Syndrome (NMS) There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated with metoclopramide.
Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated.
In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS).
Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available.
Bromocriptine and dantrolene sodium have been used in treatment of NMS, but their effectiveness have not been established (see ADVERSE REACTIONS ).
DRUG INTERACTIONS
Drug Interactions: The effects of metoclopramide on gastrointestinal motility are antagonized by anticholinergic drugs and narcotic analgesics.
Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics or tranquilizers.
The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors.
Absorption of drugs from the stomach may be diminished (e.g., digoxin) by metoclopramide, whereas the rate and/or extent of absorption of drugs from the small bowel may be increased (e.g., acetaminophen, tetracycline, levodopa, ethanol, cyclosporine).
Gastroparesis (gastric stasis) may be responsible for poor diabetic control in some patients.
Exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia.
Because the action of metoclopramide will influence the delivery of food to the intestines and thus the rate of absorption, insulin dosage or timing of dosage may require adjustment.
OVERDOSAGE
Symptoms of overdosage may include drowsiness, disorientation and extrapyramidal reactions.
Anticholinergic or antiparkinson drugs or antihistamines with anticholinergic properties may be helpful in controlling the extrapyramidal reactions.
Symptoms are self-limiting and usually disappear within 24 hours.
Hemodialysis removes relatively little metoclopramide, probably because of the small amount of the drug in blood relative to tissues.
Similarly, continuous ambulatory peritoneal dialysis does not remove significant amounts of drug.
It is unlikely that dosage would need to be adjusted to compensate for losses through dialysis.
Dialysis is not likely to be an effective method of drug removal in overdose situations.
Unintentional overdose due to misadministration has been reported in infants and children with the use of metoclopramide oral solution.
While there was no consistent pattern to the reports associated with these overdoses, events included seizures, extrapyramidal reactions, and lethargy.
Methemoglobinemia has occurred in premature and full-term neonates who were given overdoses of metoclopramide (1 to 4 mg/kg/day orally, intramuscularly or intravenously for 1 to 3 or more days).
Methemoglobinemia can be reversed by the intravenous administration of methylene blue.
However, methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal (see PRECAUTIONS – Other Special Populations ).
DESCRIPTION
Metoclopramide hydrochloride, USP is a white or practically white, crystalline, odorless or practically odorless powder.
It is very soluble in water, freely soluble in alcohol, sparingly soluble in chloroform, practically insoluble in ether.
Chemically, it is 4-amino-5-chloro-N-[2-(diethylamino) ethyl]-2-methoxybenzamide monohydrochloride monohydrate.
Its structural formula is as follows: Each tablet for oral administration contains metoclopramide hydrochloride, equivalent to either 5 mg or 10 mg metoclopramide.
Tablets also contain as inactive ingredients anhydrous lactose, magnesium stearate, povidone, pregelatinized starch, sodium starch glycolate and (5 mg only) D&C Yellow #10 and FD&C Blue #1.
Structural formula for metoclopramide hydrochloride
HOW SUPPLIED
Product: 63739-103 NDC: 63739-103-10 10 TABLET in a BLISTER PACK / 10 in a BOX, UNIT-DOSE Product: 63739-293 NDC: 63739-293-10 10 TABLET in a BLISTER PACK / 10 in a BOX, UNIT-DOSE
GERIATRIC USE
Geriatric Use Clinical studies of metoclopramide did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects.
The risk of developing parkinsonian-like side effects increases with ascending dose.
Geriatric patients should receive the lowest dose of metoclopramide that is effective.
If parkinsonian-like symptoms develop in a geriatric patient receiving metoclopramide, metoclopramide should generally be discontinued before initiating any specific anti-parkinsonian agents (see WARNINGS and DOSAGE AND ADMINISTRATION – For the Relief of Symptomatic Gastroesophageal Reflux ).
The elderly may be at greater risk for tardive dyskinesia (see WARNINGS – Tardive Dyskinesia ).
Sedation has been reported in metoclopramide users.
Sedation may cause confusion and manifest as over-sedation in the elderly (see CLINICAL PHARMACOLOGY , PRECAUTIONS – Information for Patients and ADVERSE REACTIONS – CNS Effects ).
Metoclopramide is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function (see DOSAGE AND ADMINISTRATION – USE IN PATIENTS WITH RENAL OR HEPATIC IMPAIRMENT ).
For these reasons, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased renal function, concomitant disease, or other drug therapy in the elderly (see DOSAGE AND ADMINISTRATION – For the Relief of Symptomatic Gastroesophageal Reflux and Use in Patients with Renal or Hepatic Impairment ).
INDICATIONS AND USAGE
The use of metoclopramide tablets, USP is recommended for adults only.
Therapy should not exceed 12 weeks in duration.
Symptomatic Gastroesophageal Reflux: Metoclopramide tablets, USP are indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux who fail to respond to conventional therapy.
The principal effect of metoclopramide is on symptoms of postprandial and daytime heartburn with less observed effect on nocturnal symptoms.
If symptoms are confined to particular situations, such as following the evening meal, use of metoclopramide as single doses prior to the provocative situation should be considered, rather than using the drug throughout the day.
Healing of esophageal ulcers and erosions has been endoscopically demonstrated at the end of a 12-week trial using doses of 15 mg q.i.d.
As there is no documented correlation between symptoms and healing of esophageal lesions, patients with documented lesions should be monitored endoscopically.
Diabetic Gastroparesis (Diabetic Gastric Stasis): Metoclopramide tablets, USP are indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis.
The usual manifestations of delayed gastric emptying (e.g., nausea, vomiting, heartburn, persistent fullness after meals, and anorexia) appear to respond to metoclopramide within different time intervals.
Significant relief of nausea occurs early and continues to improve over a three-week period.
Relief of vomiting and anorexia may precede the relief of abdominal fullness by one week or more.
PEDIATRIC USE
Pediatric Use: Safety and effectiveness in pediatric patients have not been established (see OVERDOSAGE ) Care should be exercised in administering metoclopramide to neonates since prolonged clearance may produce excessive serum concentrations (see CLINICAL PHARMACOLOGY – Pharmacokinetics ).
In addition, neonates have reduced levels of NADH-cytochrome b 5 reductase which, in combination with the aforementioned pharmacokinetic factors, make neonates more susceptible to methemoglobinemia (see OVERDOSAGE ).
The safety profile of metoclopramide in adults cannot be extrapolated to pediatric patients.
Dystonias and other extrapyramidal reactions associated with metoclopramide are more common in the pediatric population than in adults.
(See WARNINGS and ADVERSE REACTIONS – Extrapyramidal Reactions.
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NUSRING MOTHERS
Nursing Mothers: Metoclopramide is excreted in human milk.
Caution should be exercised when metoclopramide is administered to a nursing mother.
BOXED WARNING
WARNING: TARDIVE DYSKINESIA Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible.
The risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dose.
Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia.
There is no known treatment for tardive dyskinesia.
In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped.
Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.
See WARNINGS
INFORMATION FOR PATIENTS
Information for Patients: The use of metoclopramide is recommended for adults only.
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.
For additional information, patients should be instructed to see the Medication Guide for metoclopramide tablets.
DOSAGE AND ADMINISTRATION
Therapy with metoclopramide tablets should not exceed 12 weeks in duration.
For the Relief of Symptomatic Gastroesophageal Reflux: Administer from 10 mg to 15 mg metoclopramide hydrochloride, USP orally up to q.i.d.
30 minutes before each meal and at bedtime, depending upon symptoms being treated and clinical response (see CLINICAL PHARMACOLOGY and INDICATIONS AND USAGE ).
If symptoms occur only intermittently or at specific times of the day, use of metoclopramide in single doses up to 20 mg prior to the provoking situation may be preferred rather than continuous treatment.
Occasionally, patients (such as elderly patients) who are more sensitive to the therapeutic or adverse effects of metoclopramide will require only 5 mg per dose.
Experience with esophageal erosions and ulcerations is limited, but healing has thus far been documented in one controlled trial using q.i.d.
therapy at 15 mg per dose, and this regimen should be used when lesions are present, so long as it is tolerated (see ADVERSE REACTIONS ).
Because of the poor correlation between symptoms and endoscopic appearance of the esophagus, therapy directed at esophageal lesions is best guided by endoscopic evaluation.
Therapy longer than 12 weeks has not been evaluated and cannot be recommended.
For the Relief of Symptoms Associated with Diabetic Gastroparesis (Diabetic Gastric Stasis) Administer 10 mg of metoclopramide 30 minutes before each meal and at bedtime for two to eight weeks, depending upon response and the likelihood of continued well-being upon drug discontinuation.
The initial route of administration should be determined by the severity of the presenting symptoms.
If only the earliest manifestations of diabetic gastric stasis are present, oral administration of metoclopramide may be initiated.
However, if severe symptoms are present, therapy should begin with metoclopramide injection (consult labeling of the injection prior to initiating parenteral administration).
Administration of the metoclopramide injection up to 10 days may be required before symptoms subside, at which time oral administration may be instituted.
Since diabetic gastric stasis is frequently recurrent, metoclopramide therapy should be reinstituted at the earliest manifestation.
Use in Patients with Renal or Hepatic Impairment: Since metoclopramide is excreted principally through the kidneys, in those patients whose creatinine clearance is below 40 mL/min, therapy should be initiated at approximately one-half the recommended dosage.
Depending upon clinical efficacy and safety considerations, the dosage may be increased or decreased as appropriate.
See OVERDOSAGE section for information regarding dialysis.
Metoclopramide undergoes minimal hepatic metabolism, except for simple conjugation.
Its safe use has been described in patients with advanced liver disease whose renal function was normal.