Reglan Information
Reglan (Metoclopramide) Description
Metoclopramide hydrochloride is a white crystalline, odorless substance, freely soluble in water. Chemically, it is 4‑amino-5-chloro‑N‑[2‑(diethylamino)ethyl]‑2‑methoxy benzamide monohydrochloride monohydrate. Molecular weight: 354.3.
Reglan (Metoclopramide) Injection (metoclopramide injection, USP) is a clear, colorless, sterile solution with a pH of 4.5-6.5 for intravenous (IV) or intramuscular (IM) administration.
This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.
2 mL single dose vials; 10 mL and 30 mL single dose vials
Each 1 mL contains: Metoclopramide base 5 mg (as the monohydrochloride monohydrate), Sodium Chloride, USP 8.5 mg, Water for Injection, USP q.s. pH adjusted, when necessary, with hydrochloric acid and/or sodium hydroxide.
Reglan (Metoclopramide) Clinical Pharmacology
Metoclopramide stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Its mode of action is unclear. It seems to sensitize tissues to the action of acetylcholine. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.
Metoclopramide increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.
In patients with gastroesophageal reflux and low LESP (lower esophageal sphincter pressure), single oral doses of metoclopramide produce dose-related increases in LESP. Effects begin at about 5 mg and increase through 20 mg (the largest dose tested). The increase in LESP from a 5 mg dose lasts about 45 minutes and that of 20 mg lasts between 2 and 3 hours. Increased rate of stomach emptying has been observed with single oral doses of 10 mg.
The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors. Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like l-dopa or apomorphine which are known to increase dopamine levels or to possess dopamine-like effects. Metoclopramide also abolishes the slowing of gastric emptying caused by apomorphine.
Like the phenothiazines and related drugs, which are also dopamine antagonists, metoclopramide produces sedation and may produce extrapyramidal reactions, although these are comparatively rare (see ). Metoclopramide inhibits the central and peripheral effects of apomorphine, induces release of prolactin and causes a transient increase in circulating aldosterone levels, which may be associated with transient fluid retention.
The onset of pharmacological action of metoclopramide is 1 to 3 minutes following an intravenous dose, 10 to 15 minutes following intramuscular administration, and 30 to 60 minutes following an oral dose; pharmacological effects persist for 1 to 2 hours.
Reglan (Metoclopramide) 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.
Reglan (Metoclopramide) Warnings
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 ).
Reglan (Metoclopramide) Precautions
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.
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.
Because metoclopramide produces a transient increase in plasma aldosterone, certain patients, especially those with cirrhosis or congestive heart failure, may be at risk of developing fluid retention and volume overload. If these side effects occur at any time during metoclopramide therapy, the drug should be discontinued.
Intravenous administration of Reglan (Metoclopramide) Injection 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. This possibility should be considered and weighed when deciding whether to use metoclopramide or nasogastric suction in the prevention of postoperative nausea and vomiting.
A patient Medication Guide is available for Reglan (Metoclopramide) Injection. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. Refer to accompanying Medication Guide.
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.
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.
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 , 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.
Safety and effectiveness in pediatric patients have not been established except as stated to facilitate small bowel intubation (see and ).
Care should be exercised in administering metoclopramide to neonates since prolonged clearance may produce excessive serum concentrations (see ). In addition, neonates have reduced levels of NADH-cytochrome b reductase which, in combination with the aforementioned pharmacokinetic factors, make neonates more susceptible to methemoglobinemia (see ).
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 and .)
Clinical studies of Reglan (Metoclopramide) Injection 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 Reglan (Metoclopramide) Injection that is effective. If parkinsonian-like symptoms develop in a geriatric patient receiving Reglan (Metoclopramide) Injection, Reglan (Metoclopramide) Injection should generally be discontinued before initiating any specific anti-parkinsonian agents (see ).
The elderly may be at greater risk for tardive dyskinesia (see ).
Sedation has been reported in Reglan (Metoclopramide) Injection users. Sedation may cause confusion and manifest as over-sedation in elderly (see , and ).
Reglan (Metoclopramide) Injection 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 ).
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 ).
Reglan (Metoclopramide) Adverse Reactions
In general, the incidence of adverse reactions correlates with the dose and duration of metoclopramide administration. The following reactions have been reported, although in most instances, data do not permit an estimate of frequency:
Acute dystonic reactions, the most common type of EPS associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day. In cancer chemotherapy patients receiving 1‑2 mg/kg per dose, the incidence is 2% in patients over the ages of 30‑35, and 25% or higher in pediatric patients and adult patients less than 30 years of age who have not had prophylactic administration of diphenhydramine. Symptoms include involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions), and, rarely, stridor and dyspnea possibly due to laryngospasm; ordinarily these symptoms are readily reversed by diphenhydramine (see ).
Parkinsonian-like symptoms may include bradykinesia, tremor, cogwheel rigidity, mask-like facies (see ).
Tardive dyskinesia most frequently is characterized by involuntary movements of the tongue, face, mouth, or jaw, and sometimes by involuntary movements of the trunk and/or extremities; movements may be choreoathetotic in appearance (see ).
Motor restlessness (akathisia) may consist of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, foot tapping. These symptoms may disappear spontaneously or respond to a reduction in dosage.
Visual disturbances. Porphyria.
Transient flushing of the face and upper body, without alterations in vital signs, following high doses intravenously.
Reglan (Metoclopramide) 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 Reglan (Metoclopramide) syrup. 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 (1‑4 mg/kg/day orally, intramuscularly or intravenously for 1‑3 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 ).
Reglan (Metoclopramide) Dosage And Administration
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 Reglan (Metoclopramide) Injection (IM or IV). Doses of 10 mg may be administered slowly by the intravenous route over a 1- to 2-minute period.
Administration of Reglan (Metoclopramide) Injection (metoclopramide injection, USP) up to 10 days may be required before symptoms subside, at which time oral administration of metoclopramide may be instituted. The physician should make a thorough assessment of the risks and benefits prior to prescribing further metoclopramide treatment.
Intravenous infusions should be made slowly over a period of not less than 15 minutes, 30 minutes before beginning cancer chemotherapy and repeated every 2 hours for two doses, then every 3 hours for three doses.
The initial two doses should be 2 mg/kg if highly emetogenic drugs such as cisplatin or dacarbazine are used alone or in combination. For less emetogenic regimens, 1 mg/kg per dose may be adequate.
For doses in excess of 10 mg, Reglan (Metoclopramide) Injection should be diluted in 50 mL of a parenteral solution.
The preferred parenteral solution is Sodium Chloride Injection (normal saline), which when combined with Reglan (Metoclopramide) Injection, can be stored frozen for up to 4 weeks. Reglan (Metoclopramide) Injection is degraded when admixed and frozen with Dextrose-5% in Water. Reglan (Metoclopramide) Injection diluted in Sodium Chloride Injection, Dextrose-5% in Water, Dextrose-5% in 0.45% Sodium Chloride, Ringer’s Injection, or Lactated Ringer’s Injection may be stored up to 48 hours (without freezing) after preparation if protected from light. All dilutions may be stored unprotected from light under normal light conditions up to 24 hours after preparation.
If acute dystonic reactions should occur, inject 50 mg Benadryl (diphenhydramine hydrochloride) intramuscularly, and the symptoms usually will subside.
If the tube has not passed the pylorus with conventional maneuvers in 10 minutes, a single dose (undiluted) may be administered slowly by the intravenous route over a 1- to 2-minute period.
The recommended single dose is: Pediatric patients above 14 years of age and adults — 10 mg metoclopramide base. Pediatric patients (6-14 years of age) — 2.5 to 5 mg metoclopramide base; (under 6 years of age) — 0.1 mg/kg metoclopramide base.
In patients where delayed gastric emptying interferes with radiological examination of the stomach and/or small intestine, a single dose may be administered slowly by the intravenous route over a 1- to 2-minute period.
For dosage, see intubation above.
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 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.
NOTE:
Reglan (Metoclopramide) Admixtures Compatibilities
Reglan (Metoclopramide) Injection (metoclopramide injection, USP) is compatible for mixing and injection with the following dosage forms to the extent indicated below:
Reglan (Metoclopramide) How Supplied
Reglan (Metoclopramide) Injection (metoclopramide injection, USP) 5 mg metoclopramide base (as the monohydrochloride monohydrate) per mL; available in:
2 mL single dose vials in cartons of 25 (NDC 60977-451-01),
10 mL single dose vials in cartons of 25 (NDC 60977-451-02),
30 mL single dose vials in cartons of 25 (NDC 60977-451-03).
Store vials in carton until used. Do not store open single dose vials for later use, as they contain no preservative.
This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.
Reglan (Metoclopramide) is a trademark of Alaven Pharmaceutical LLC, its agents or assignees.
ESI logo is a trademark of Baxter International, Inc.
Manufactured by
Deerfield, IL 60015 USA
For Product Inquiry 1 800 933 0303
Revised August 2010
MLT00066,I
Reglan (Metoclopramide) Medication Guide
You or your caregiver should read the Medication Guide before you start receiving Reglan (Metoclopramide) Injection and before you get another dose of Reglan (Metoclopramide) Injection. There may be new information. If you take another product that contains metoclopramide (such as Reglan (Metoclopramide) tablets, Reglan (Metoclopramide) ODT tablets, or metoclopramide oral syrup), you should read the Medication Guide that comes with that product. Some of the information may be different. This Medication Guide does not take the place of talking to your doctor about your medical condition or your treatment.
Reglan (Metoclopramide) Injection can cause serious side effects, including:
Your chances for getting TD go up:
It is not possible for your doctor to know if will get TD if you take Reglan (Metoclopramide) Injection.
Call your doctor right away if you get movements you can not stop or control, such as:
See the section “What are the possible side effects of Reglan (Metoclopramide) Injection?” for more information about side effects.
Reglan (Metoclopramide) Injection is a prescription medicine used to:
Do not receive Reglan (Metoclopramide) Injection if you:
If you are not sure if your medicine is one listed above, ask your doctor or pharmacist. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.
You may have more side effects the longer you take Reglan (Metoclopramide) Injection and the more Reglan (Metoclopramide) Injection you take.
Tell your doctor about any side effects that bother you or do not go away. These are not all the possible side effects of Reglan (Metoclopramide) Injection.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.
This Medication Guide summarizes the most important information about Reglan (Metoclopramide) Injection. If you would like more information about Reglan (Metoclopramide) Injection, talk with your doctor. You can ask your doctor or pharmacist for information about Reglan (Metoclopramide) Injection that is written for healthcare professionals. For more information, call Baxter Healthcare at 1-800-933-0303.
Revised April 2010
ESI logoManufactured by: Deerfield, IL 60015 USA
Printed in USA
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Reglan (Metoclopramide) and Reglan (Metoclopramide) ODT are trademarks of Alaven Pharmaceutical LLC, its agents or assignees.Baxter and the ESI logo are trademarks of Baxter International Inc.
MGMLT00066,B
Reglan (Metoclopramide) Package Label - Principal Display Panel
NDC 60977-451-17
2 mL Single Dose Vial
by Deerfield, IL 60015 USA
462-122-01
(01)00360977451176
LOT
EXP.
LOT
EXP.
To open—Cut seal along dotted line.
NDC 60977-451-01
Rx only
25 x 2 mL Single Dose Vials
ESI logo
Manufactured by Deerfield, IL 60015 USA
462-123-03
For dosage and other directions foruse, consult accompanyingproduct literature.
Dispense the accompanyingMedication Guide to each patient.
STORE VIALS IN CARTONUNTIL USED.
(01)00360977451015
