metoclopramide 10 MG per 2 ML Injection
Generic Name: METOCLOPRAMIDE HYDROCHLORIDE
Brand Name: Metoclopramide hydrochloride
- Substance Name(s):
- METOCLOPRAMIDE HYDROCHLORIDE
WARNINGS
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 ).
Extrapyramidal Symptoms (EPS) Acute Dystonic Reactions 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 pediatric patients and adult patients less than 30 years of age and are even more frequent at the higher doses used in prophylaxis of vomiting due to cancer chemotherapy.
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 Benadryl® (diphenhydramine hydrochloride) intramuscularly, and they usually will subside.
Cogentin® (benztropine mesylate), 1 to 2 mg intramuscularly, may also be used to reverse these reactions.
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 patterns showed that about 20% of patients who used metoclopramide took it for 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 or 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.
Parkinsonian-like Symptoms Parkinsonian-like symptoms, including bradykinesia, tremor, cogwheel rigidity, or mask-like facies, 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.
Depression 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.
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 (1-4 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 PRECAUTIONS – Other Special Populations ).
DESCRIPTION
Metoclopramide hydrochloride, USP 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 and has the following structural formula: C14H22ClN3O2•HCl•H2O M.W.
354.3 C14H22ClN3O2•HCl•H2O M.W.
354.3 Metoclopramide injection USP is a clear, colorless, sterile solution with a pH of 2.5-6.5 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.
Metoclopramide injection USP is supplied in 2 mL single-use vials.
Each 1 mL contains: Metoclopramide base 5 mg (present as the hydrochloride), Sodium Chloride, USP 8.5 mg, Water for Injection, USP q.s.
pH is adjusted with hydrochloric acid and/or sodium hydroxide if necessary.
Structural Formula
HOW SUPPLIED
Metoclopramide Injection USP is available overbagged with 5 vials per bag, NDC 55154-0450-5.
NDC Number Metoclopramide Injection USP Volume 55154-0450-5 5 mg/mL 2 mL in a 2 mL single-use vial PROTECT FROM LIGHT.
Store in shelf pack until time of use.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Inspect the vial before use and discard if either color or particulate is observed.
Dilutions may be stored unprotected from light under normal light conditions for up to 24 hours after preparation.
Do not freeze.
Do not store open single-use vials for later use, as they contain no preservative.
Discard unused portion.
Rev.
B 10/2013 Teva Parenteral Medicines, Inc.
Irvine, CA 92618 Repackaged By: Cardinal Health Zanesville, OH 43701 L35627090915
GERIATRIC USE
Geriatric Use Clinical studies of metoclopramide injection USP 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 injection USP that is effective.
If parkinsonian-like symptoms develop in a geriatric patient receiving metoclopramide injection USP, metoclopramide injection USP should generally be discontinued before initiating any specific anti-parkinsonian agents (see WARNINGS ).
The elderly may be at greater risk for tardive dyskinesia (see WARNINGS – Tardive Dyskinesia ).
Sedation has been reported in metoclopramide injection USP users.
Sedation may cause confusion and manifest as over-sedation in elderly (see CLINICAL PHARMACOLOGY, PRECAUTIONS – Information for Patients and ADVERSE REACTIONS – CNS Effects ).
Metoclopramide injection USP 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 Use in Patients With Renal or Hepatic Impairment ).
INDICATIONS AND USAGE
Diabetic Gastroparesis (Diabetic Gastric Stasis) Metoclopramide injection USP is indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis.
The Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy Metoclopramide injection USP is indicated for the prophylaxis of vomiting associated with emetogenic cancer chemotherapy.
The Prevention of Postoperative Nausea and Vomiting Metoclopramide injection USP is indicated for the prophylaxis of postoperative nausea and vomiting in those circumstances where nasogastric suction is undesirable.
Small Bowel Intubation Metoclopramide injection USP may be used to facilitate small bowel intubation in adults and pediatric patients in whom the tube does not pass the pylorus with conventional maneuvers.
Radiological Examination Metoclopramide injection USP may be used to stimulate gastric emptying and intestinal transit of barium in cases where delayed emptying interferes with radiological examination of the stomach and/or small intestine.
PEDIATRIC USE
Pediatric Use Safety and effectiveness in pediatric patients have not been established except as stated to facilitate small bowel intubation (see OVERDOSAGE and DOSAGE AND ADMINISTRATION ).
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 b5 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 .)
PREGNANCY
Pregnancy Category B Reproduction studies performed in rats, mice and rabbits by the IM, IV, subcutaneous (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.
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 A patient Medication Guide is available for metoclopramide injection USP.
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.
DOSAGE AND ADMINISTRATION
For the Relief of Symptoms Associated with Diabetic Gastroparesis (Diabetic Gastric Stasis) 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 USP (IM or IV).
Doses of 10 mg may be administered slowly by the intravenous route over a 1- to 2-minute period.
Administration of 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.
For the Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy 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, metoclopramide injection USP should be diluted in 50 mL of a parenteral solution.
The preferred parenteral solution is Sodium Chloride Injection (normal saline), which when combined with metoclopramide injection USP, can be stored frozen for up to 4 weeks.
Metoclopramide injection USP is degraded when admixed and frozen with Dextrose-5% in Water.
Metoclopramide injection USP 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.
For the Prevention of Postoperative Nausea and Vomiting Metoclopramide injection USP should be given intramuscularly near the end of surgery.
The usual adult dose is 10 mg; however, doses of 20 mg may be used.
To Facilitate Small Bowel Intubation 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.
To Aid in Radiological Examinations 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.
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.
NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
ADMIXTURES COMPATIBILITIES Metoclopramide injection USP is compatible for mixing and injection with the following dosage forms to the extent indicated below: Physically and Chemically Compatible Up to 48 Hours Cimetidine Hydrochloride (SK&F), Mannitol, USP (Abbott), Potassium Acetate, USP (Invenex), Potassium Phosphate, USP (Invenex).
Physically Compatible Up to 48 Hours Ascorbic Acid, USP (Abbott), Benztropine Mesylate, USP (MS&D), Cytarabine, USP (Upjohn), Dexamethasone Sodium Phosphate, USP (ESI, MS&D), Diphenhydramine Hydrochloride, USP (Parke-Davis), Doxorubicin Hydrochloride, USP (Adria), Heparin Sodium, USP (ESI), Hydrocortisone Sodium Phosphate (MS&D), Lidocaine Hydrochloride, USP (ESI), Multi-Vitamin Infusion (must be refrigerated-USV), Vitamin B Complex with Ascorbic Acid (Roche).
Physically Compatible Up to 24 Hours (Do not use if precipitation occurs) Clindamycin Phosphate, USP (Upjohn), Cyclophosphamide, USP (Mead-Johnson), Insulin, USP (Lilly).
Conditionally Compatible (Use within one hour after mixing or may be infused directly into the same running IV line) Ampicillin Sodium, USP (Bristol), Cisplatin (Bristol), Erythromycin Lactobionate, USP (Abbott), Methotrexate Sodium, USP (Lederle), Penicillin G Potassium, USP (Squibb), Tetracycline Hydrochloride, USP (Lederle).
Incompatible (Do Not Mix) Cephalothin Sodium, USP (Lilly), Chloramphenicol Sodium, USP (Parke-Davis), Sodium Bicarbonate, USP (Abbott).