Metoclopramide Hydrochloride

Pronunciation

Pronunciation: MET-oh-KLOE-pra-mide HYE-droe-KLOR-ide
Class: Antidopaminergic, GI stimulant

Trade Names

Metoclopramide Hydrochloride
- Solution 5 mg per 5 mL

Metozolv ODT
- Tablets, orally disintegrating 5 mg
- Tablets, orally disintegrating 10 mg

Reglan
- Tablets 5 mg
- Tablets 10 mg
- Injection, solution 5 mg/mL

APO-Metoclop (Canada)
Nu-Metoclopramide (Canada)

Pharmacology

Stimulates upper GI tract motility, resulting in accelerated gastric emptying and intestinal transit, and increased resting tone of lower esophageal sphincter. Exerts antiemetic properties through antagonism of central and peripheral dopamine receptors.

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Pharmacokinetics

Absorption

Rapidly and well absorbed. Absolute oral bioavailability is approximately 80%; T max is 1 to 2 h (oral). Administration of the orally disintegrating tablet after a high-fat meal results in a 17% lower peak blood level and delays T max to 3 h.

Distribution

Approximately 30% is protein bound; Vd is approximately 3.5 L/kg.

Elimination

Approximately 85% of oral dose appears in urine within 72 h (50% is present as free or conjugated metoclopramide). The half-life is 5 to 6 h.

Onset

Onsets are 1 to 3 min (IV), 10 to 15 min (IM), and 30 to 60 min (oral).

Duration

Duration is 1 to 2 h.

Special Populations

Renal Function Impairment

Reduced plasma Cl, renal Cl, and nonrenal Cl, and increased elimination half-life.

Hepatic Function Impairment

No data available.

Children

Prolonged Cl in neonates.

Indications and Usage

PO

Acute and recurrent diabetic gastroparesis; short-term therapy of symptomatic, documented gastroesophageal reflux disease (GERD) in adults who fail to respond to conventional therapy.

Parenteral

Prevention of nausea and vomiting associated with emetogenic cancer chemotherapy; prevention of postoperative nausea and vomiting when nasogastric suction is undesirable; facilitation of small bowel intubation when tube does not pass pylorus with conventional maneuvers; acute and recurrent diabetic gastric stasis; stimulation of gastric emptying and intestinal transit of barium where delayed emptying interferes with radiological examination of the stomach and/or small intestine.

Unlabeled Uses

Gastric bezoars, hiccups, improvement in lactation, migraines, nausea/vomiting of pregnancy, opioid-induced nausea and vomiting, Tourette syndrome, vascular headache.

Contraindications

Patients in whom increase in GI motility could be harmful (eg, in presence of GI hemorrhage, mechanical obstruction, perforation); pheochromocytoma; epilepsy; patients receiving drugs likely to cause extrapyramidal reactions; known sensitivity or intolerance to the drug.

Dosage and Administration

Aid in Radiological Examination
Adults

IV 10 mg undiluted administered as a single dose over 1 to 2 min.

Diabetic Gastroparesis
Adults PO

10 mg administered 30 min before each meal and at bedtime for 2 to 8 wk.

IM / IV

10 mg; administer IV over 1 to 2 min.

Facilitate Small Bowel Intubation
Adults and Children 14 years of age and older

IV 10 mg undiluted administered as a single dose over 1 to 2 min.

Children 6 to 14 years of age

IV 2.5 to 5 mg undiluted administered as a single dose over 1 to 2 min.

Children younger than 6 years of age

IV 0.1 mg/kg undiluted administered as a single dose over 1 to 2 min.

Gastroesophageal Reflux
Adults

PO 10 to 15 mg up to 4 times a day (30 minutes before each meal and at bedtime). If symptoms occur only intermittently or at specific times of the day, a single dose of 20 mg prior may be preferred. Patients who are more sensitive to the therapeutic or adverse effects (elderly patients) will require only 5 mg per dose.

Prevention of Nausea and Vomiting Caused by Emetogenic Chemotherapy
Adults

IV The initial 2 doses should be 2 mg/kg if highly emetogenic drugs are used alone or in combination. For less emetogenic regimens, 1 mg/kg dose may be adequate. Give 30 min before beginning cancer chemotherapy and repeat every 2 h for 2 doses, then every 3 h for 3 doses.

Prevention of Postoperative Nausea and Vomiting
Adults

IM 10 to 20 mg given near the end of surgery

Renal Function Impairment

Reduce initial dose by 50% in patients with CrCl less than 40 mL/min. Titrate subsequent doses based on patient response.

General Advice

  • Administer tablets 30 min before each meal and at bedtime when used for gastroparesis and GERD.
  • Administer orally disintegrating tablets at least 30 min before food. Place on tongue and allow to disintegrate. If tablet should break or crumble while handling, discard and remove a new tablet.
  • Therapy with tablets should not exceed 12 wk in duration.
  • If acute dystonic reactions occur, inject diphenhydramine 50 mg IM.
  • Incompatibilities for injection solution include the following: cephalothin, chloramphenicol, sodium bicarbonate. Refer to the manufacturer's package insert for compatible solutions.
  • Dilute the injection solution in 50 mL of a parenteral solution (preferably sodium chloride injection) for doses in excess of 10 mg.
  • Administer IV injections of undiluted metoclopramide slowly, allowing 1 to 2 min for 10 mg.
  • Administer IV injections of diluted metoclopramide slowly over a period of not less than 15 min.
  • Metoclopramide injection is light sensitive. Inspect before use and discard if either color or particulate is observed.

Storage/Stability

Store between 68° and 77°F. Store vials in carton until used. Do not store open single-dose vials for later use; they contain no preservative. Dilutions may be stored unprotected from light under normal light conditions up to 24 h after preparation. Stability of diluted metoclopramide is dependent on solution used. Refer to manufacturer's package insert for guidelines.

Drug Interactions

Acetaminophen, cyclosporine, ethanol, levodopa, tetracycline

Metoclopramide may increase oral bioavailability or absorption of these drugs. Observe patients for adverse reactions and adjust the dose of these agents as needed.

Anticholinergic, opioid analgesics

May decrease effect of metoclopramide on gastric emptying. Observe patients for a decrease or loss of metoclopramide effects. Adjust the metoclopramide dose as needed.

Cabergoline

Metoclopramide may decrease the hypoprolactinemic effects of cabergoline. Avoid coadministration.

Cimetidine

Bioavailability of cimetidine may be reduced because of decreased absorption as a result of faster gastric transit time. Consider administering cimetidine at least 2 hours before metoclopramide.

CNS depressants (eg, alcohol, anesthetics, barbiturates, opiates, sedatives)

May potentiate CNS depressant effects of metoclopramide. Caution patients of the possible increase in sedative effects. Adjust the dose of these agents as needed.

Cyclosporine

A faster gastric emptying time may allow for an increase in cyclosporine absorption, possibly increasing its immunosuppressive and toxic effects. Measure cyclosporine concentrations when starting or stopping metoclopramide. Adjust the cyclosporine dose as needed.

Digoxin

Absorption may be diminished. Capsules, elixirs, and tablets with a high dissolution rate are least affected and are less likely to interact.

Disulfiram

Because metoclopramide syrup contains a small amount of alcohol, there is the possibility of an acute and severe alcohol intolerance reaction. Avoid coadministration of metoclopramide syrup in patients receiving disulfiram.

Levodopa

These agents have opposite effects on dopamine receptors. The bioavailability of levodopa may be increased, and levodopa may decrease the effects of metoclopramide on gastric emptying and lower esophageal pressure. Metoclopramide is relatively contraindicated in patients with Parkinson disease.

MAOIs

Because metoclopramide releases catecholamines in patients with essential hypertension, use cautiously, if at all, in patients receiving MAOIs.

Pergolide

Metoclopramide may decrease the pharmacologic effects of pergolide. Avoid coadministration.

Serotonin reuptake inhibitors (eg, sertraline, venlafaxine)

Metoclopramide plasma concentrations may be elevated because of enzyme inhibition, increasing the pharmacologic effects and adverse reactions. In addition, the risk of serotonin syndrome occurrence may be increased. Observe the patient for an increase in adverse reactions. If serotonin syndrome occurs, immediate medical attention is required.

Succinylcholine

By inhibiting plasma cholinesterase, metoclopramide may prolong neuromuscular blocking effects such as respiratory depression and paralysis. Use with caution, and closely monitor neuromuscular function. Provide mechanical respiratory support if needed.

Adverse Reactions

Cardiovascular

Acute CHF, AV block, bradycardia, fluid retention, hypertension, hypotension, supraventricular tachycardia.

CNS

Drowsiness, fatigue, lassitude, restlessness (10%); headache (5%); dizziness (4%); somnolence (3%); confusion, depression with suicidal ideation, extrapyramidal symptoms, hallucinations, insomnia, NMS, Parkinson-like symptoms (eg, bradykinesia, cogwheel rigidity, mask-like facies, tremor), tardive dyskinesia.

Dermatologic

Transient flushing of face or upper body with high IV doses.

Endocrine

Elevation of aldosterone, which make cause fluid retention; galactorrhea, gynecomastia, hyperprolactinemia.

GI

Nausea (6%); vomiting (2%); bowel disturbances, primarily diarrhea.

Genitourinary

Amenorrhea, impotence, urinary frequency, urinary incontinence.

Hepatic

Hepatotoxicity (rare).

Hematologic

Agranulocytosis, leukopenia, methemoglobinemia, neutropenia, sulfhemoglobinemia.

Hypersensitivity

Angioneurotic edema, including glossal or laryngeal edema (rare); bronchospasm, rash, urticaria.

Musculoskeletal

Motor restlessness (akathisia).

Miscellaneous

Porphyria, visual disturbances.

Precautions

Warnings

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.

Discontinue metoclopramide therapy 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.

Avoid treatment with metoclopramide for longer than 12 wk in all but rare cases in which therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.


Pregnancy

Category B .

Lactation

Excreted in breast milk; has been used as a lactation stimulant.

Children

Safety and efficacy in children have not been established except to facilitate small bowel intubation. Methemoglobinemia has occurred in newborns.

Elderly

Increased risk of developing Parkinson-like effects, tardive dyskinesia, or oversedation; use lowest effective dose.

Carcinogenesis

Because the drug elevates serum prolactin concentration, use caution if administration of metoclopramide is considered in patient with previously detected breast cancer.

Special Risk Patients

Patients with NADH-cytochrome b 5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered. In patients with G-6-PD deficiency who experience metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended.

Anastomosis or closure of gut

Drug could theoretically put increased pressure on suture lines after gut anastomosis or closure.

Depression

Depression has occurred with or without history of depression. Symptoms have ranged from mild to severe and included suicidal ideation and suicide.

Extrapyramidal symptoms

Manifest primarily as acute dystonic reactions, occurring in approximately 0.2% of patients. Usually seen during first 24 to 48 h and more frequently in children and young adults or at higher doses.

Fluid retention/volume overload

Certain patients, especially those with cirrhosis or CHF, may be at risk of developing fluid retention and volume overload.

Hypertension

Use with caution.

NMS

There have been rare reports of an uncommon but potentially fatal symptom complex, sometimes referred to as NMS, associated with metoclopramide. Clinical manifestations of NMS include altered consciousness, evidence of autonomic instability (cardiac arrhythmias, diaphoresis, irregular pulse or blood pressure, and tachycardia), hyperthermia, and muscle rigidity.

Parkinson-like symptoms

Occur more commonly within first 6 mo of treatment, but also can occur after longer periods. Symptoms generally subside within 2 to 3 mo after drug discontinuation. Give drug cautiously, if at all, to patients with preexisting Parkinson disease.

Withdrawal

A withdrawal period after stopping metoclopramide could include dizziness, headaches, and/or nervousness.

Overdosage

Symptoms

Disorientation, drowsiness, extrapyramidal reactions, lethargy, seizures, methemoglobinemia (in newborns).

Patient Information

  • Instruct patient to take medication 30 min before meals and at bedtime when used for gastroparesis and GERD.
  • Administer orally disintegrating tablets at least 30 min before food. Do not repeat the dose if inadvertently taken with food. Only remove each dose from the packaging just prior to taking. Handle the tablet with dry hands and place on tongue. If tablet should break or crumble while handling, discard and remove a new tablet.
  • Advise patients that metoclopramide should not be taken for longer than 12 wk except in certain circumstances.
  • Instruct patient to report involuntary movement of eyes, face, or limbs to health care provider.
  • Caution patient to avoid intake of alcoholic beverages.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.

Copyright © 2009 Wolters Kluwer Health.

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