Metoclopramide Hydrochloride

Diabetic Gastric Stasis

Symptomatic treatment of acute and recurrent diabetic gastric stasis (gastroparesis).5 7 32 44 76 77 78 79 80 83 84 88 89 267 Successful therapy often requires long-term, intermittent use, since diabetic gastric stasis is a chronic, recurrent disease.5 9

Postsurgical Gastric Stasis

Has been used for the symptomatic treatment of acute and chronic postsurgical gastric stasis† following vagotomy and gastric resection or vagotomy and pyloroplasty.31 37 44 49 84 113 114 115 148 149 150

Prevention of Postoperative Nausea and Vomiting

Prevention of postoperative nausea and vomiting when nasogastric suction is considered undesirable.4 125 267

Prevention of Cancer Chemotherapy-induced Emesis

Used parenterally in high doses for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy including cisplatin alone or in combination with other antineoplastic agents.97 98 99 100 101 102 103 263 267

Prevention of nausea and vomiting associated with other antineoplastic agents (e.g., cyclophosphamide, dacarbazine, doxorubicin, methotrexate) and with cancer chemotherapy regimens that do not include cisplatin.103 144 145 146 147 218 263 267

ASCO does not consider metoclopramide an appropriate first-line antiemetic for any group of patients receiving chemotherapy of high emetic risk and states that this drug should be reserved for patients unable to tolerate or refractory to first-line agents (i.e., a type 3 serotonin [5-HT3] receptor antagonist [e.g., dolasetron, granisetron, ondansetron, palonosetron] with dexamethasone and aprepitant).263

ASCO states that the combination of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant is preferred in patients receiving combination chemotherapy with an anthracycline and cyclophosphamide; ASCO recommends combined therapy with a 5-HT3 receptor antagonist and dexamethasone for other chemotherapy regimens of moderate emetic risk (i.e., 31–90% incidence of emesis without antiemetics) and dexamethasone alone for chemotherapy regimens of low emetic risk (i.e., 11–30% incidence).263

In patients experiencing nausea and vomiting despite recommended prophylaxis regimens, ASCO recommends that clinicians consider adding a benzodiazepine (e.g., alprazolam, lorazepam), butyrophenone, or phenothiazine to the regimen or substituting high-dose IV metoclopramide for the 5-HT3 receptor antagonist in the regimen.263

Antiemetics can be prescribed on an as-needed basis for chemotherapy regimens with minimal emetic risk (<10% incidence of emesis without antiemetics).263

Metoclopramide has been used orally† for the prevention of chemotherapy-induced nausea and vomiting. 177 218 221 224 263 264 265 266 275 Some experts state that patients receiving oral chemotherapy requiring only as-needed (“prn”) antiemetic therapy or receiving an IV chemotherapy regimen with low emetic risk may receive oral† metoclopramide.275

Oral† metoclopramide has been effective when given in combination with dexamethasone for the prevention of delayed emesis in patients receiving chemotherapy.263 264 265 266 For prevention of delayed emesis in patients receiving cisplatin or other chemotherapy of high emetic risk, ASCO recommends the combination of dexamethasone and aprepitant.263

Intubation of the Small Intestine

Used parenterally to facilitate small intestine intubation when the tube (e.g., endoscope, biopsy tube) does not pass through the pylorus during 10 minutes of conventional maneuvers.105 106 107 109 176 267

Radiographic Examination of the Upper GI Tract

Used parenterally to stimulate gastric emptying and intestinal transit of barium when delayed emptying interferes with radiographic examination of the stomach and/or small intestine.4 43 110 184 267

Gastroesophageal Reflux

Short-term (≤12 weeks) relief of symptomatic, documented gastroesophageal reflux in adults who are unresponsive to conventional therapy (e.g., changes in lifestyle, habits, diet, weight reduction) alone.5 9 30 39 40 41 42 111 112 116 117 125 129 185 186 187 188 189 190

Regular use for this purpose has declined; proton-pump inhibitors provide greater control of acid reflux.258 273 274 Some experts recommend against use of metoclopramide for this purpose based on the drug’s adverse effect profile and lack of high-quality supporting data.273 274

Administration

Administer orally, by direct IV injection or IV infusion, or IM.5 263 267

Metoclopramide therapy should not exceed 12 weeks’ duration.5 267 268 269

Oral Administration

Metoclopramide oral solution and tablets are recommended for use in adults only.5 268 269

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

For direct IV injection, use without further dilution.267

If dose is >10 mg, dilute in 50 mL of a compatible IV solution.267

For IV infusion, manufacturer recommends dilution in 50 mL of 5% dextrose, 0.9% sodium chloride, 5% dextrose and 0.45% sodium chloride, Ringer’s, or lactated Ringer’s injection.267

Manufacturer states that 0.9% sodium chloride injection is preferred because metoclopramide hydrochloride is most stable in this solution.267

Direct IV injection: Administer each 10 mg slowly over 1–2 minutes.267 Rapid IV injection may cause transient but intense feelings of anxiety and restlessness, followed by drowsiness.267

IV infusion: Administer slowly over ≥15 minutes.267

IM Administration

Inject without further dilution.267

Dosage

Available as metoclopramide hydrochloride; dosage expressed in terms of metoclopramide.5 267

Pediatric Patients

Children <6 years of age: Usually, one 0.1-mg/kg dose given by direct IV injection.267

Children 6–14 years of age: Usually, one 2.5- to 5-mg dose given by direct IV injection.267

Children >14 years of age: Usually, one 10-mg dose given by direct IV injection.267

Adults

10 mg 4 times daily, given 30 minutes before meals and at bedtime.5 Continue for 2–8 weeks, depending on response and likelihood of continued well-being if drug is discontinued.5 Reinstitute at earliest symptom recurrence.5

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given by direct IV injection 30 minutes before meals and at bedtime.5 267 Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;5 267 however, thoroughly assess the risks and benefits prior to continuing therapy.267

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given 30 minutes before meals and at bedtime.5 267 Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;5 267 however, thoroughly assess the risks and benefits prior to continuing therapy.267

Manufacturer states that usual dose is 10 mg administered near the end of the surgical procedure; 20 mg also may be used.267

Some experts state that patients receiving IV chemotherapy regimens with low emetic risk may receive 10–40 mg of metoclopramide before the chemotherapy dose and then every 4 or 6 hours as needed.275

Some experts state that patients receiving oral chemotherapy requiring only as-needed (“prn”) antiemetic therapy may receive 10–40 mg of metoclopramide before the chemotherapy dose and then every 4 or 6 hours as needed.275

When given in combination with dexamethasone in clinical trials for the prevention of delayed emesis (i.e., vomiting occurring ≥24 hours after chemotherapy), 20–40 mg (or 0.5 mg/kg) of metoclopramide has been given 2–4 times daily for 3 or 4 days.263 264 265 266

Manufacturer states that metoclopramide usually is given by IV infusion 30 minutes before administration of chemotherapy, and then repeated every 2 hours for 2 additional doses followed by every 3 hours for 3 additional doses.267 Manufacturer states that initial 2 doses should be 2 mg/kg if highly emetogenic chemotherapy used;267 for less emetogenic drugs or regimens, initial 1-mg/kg dose may be sufficient.267 However, combinations of other antiemetic agents generally are preferred as first-line regimens in patients receiving chemotherapy of moderate or high emetic risk (see Prevention of Cancer Chemotherapy-induced Emesis under Uses). 263 275

Some experts state that patients receiving IV chemotherapy regimens with low emetic risk may receive 10–40 mg of metoclopramide before the chemotherapy dose and then every 4 or 6 hours as needed.275

Usually, one 10-mg dose given by direct IV injection.267

Usually, one 10-mg dose given by direct IV injection.267

Usually, 10–15 mg up to 4 times daily (30 minutes before each meal and at bedtime) for 4–12 weeks, depending on symptoms and response.5 Patients sensitive to therapeutic and/or adverse effects of metoclopramide may require initial dose of 5 mg.5

For intermittent symptoms or symptoms at specific times of the day, one 20-mg dose before the provoking situation may be preferred to daily administration of multiple doses.5

In patients with esophageal erosion and ulceration, 15 mg 4 times daily for 12 weeks has provided healing; monitor endoscopically because of the poor correlation between symptoms and healing.5

Prescribing Limits

Adults

Avoid use of metoclopramide for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.5 267 (See Boxed Warning and see Tardive Dyskinesia under Cautions.)

Safety and efficacy beyond 12 weeks not established; use beyond 12 weeks not recommended.5

Special Populations

Hepatic Impairment

Dosage modification does not appear to be necessary.5 267

Renal Impairment

Modify dosage according to degree of renal impairment.5 54 58 59 135 142 267

In patients with Clcr <40 mL/minute, manufacturers recommend an initial dosage of approximately 50% of the usual dosage.5 267 Subsequently, increase or decrease dosage according to response and tolerance.5 267

Geriatric Patients

Select dosage with caution, usually initiating therapy at the low end of the dosage range.5 267

Administer lowest effective dosage.5 267 In geriatric patients with gastroesophageal reflux, initial 5-mg dose may be required due to possible sensitivity to therapeutic and/or adverse effects of metoclopramide.5

Contraindications

• Mechanical obstruction or perforation or other situations in which stimulation of GI motility might be dangerous.5 267

• GI hemorrhage5 267 (however, has been used to empty the stomach of blood prior to endoscopy in patients with acute upper GI hemorrhage).4 125

• Pheochromocytoma (due to potential for hypertensive crisis).5 267

• History of seizure disorders.4 5 267

• Concomitant therapy with drugs likely to cause extrapyramidal reactions (e.g., phenothiazines, butyrophenones).4 5 267

• Known intolerance to metoclopramide.5 267

• Known hypersensitivity to metoclopramide or any ingredient in the formulation.5 267

Warnings/Precautions

Warnings

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements involving the tongue, face, mouth, or jaw, and sometimes the trunk and/or extremities, may occur; movements may be choreoathetotic in appearance.5 93 94 130 157 158 159 267 270 271 272 (See Boxed Warning.)

Reported in about 20% of patients receiving the drug for ≥12 weeks.5 267 270 271 Avoid use of metoclopramide for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.5 267 272

Although risk of developing tardive dyskinesia may be increased in geriatric patients, women, and patients with diabetes mellitus, it is not possible to predict which patients will develop metoclopramide-induced tardive dyskinesia.5 267 270 271 272 Risk of occurrence and irreversibility increases with increasing duration of therapy and total cumulative dose.5 267 271 272

Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia.5 267 270 271 There is no known effective treatment for tardive dyskinesia; however, tardive dyskinesia may remit, either partially or completely, in some patients within several weeks to months after discontinuance.5 267 271

Metoclopramide may suppress or partially suppress signs of tardive dyskinesia, thereby masking the underlying disease process; effect of this suppression on the long-term course of tardive dyskinesia is unknown.5 267 Do not use metoclopramide for symptomatic control of tardive dyskinesia.5 267

Potential for extrapyramidal reactions,4 5 90 91 125 169 205 206 207 267 especially in pediatric patients and adults <30 years of age or when high doses (e.g., IV doses for prophylaxis of cancer chemotherapy-induced nausea and vomiting) are administered.5 91 169 267

Commonly manifested as acute dystonic reactions or akathisia; stridor and dyspnea (possibly due to laryngospasm) reported rarely.5 267

Generally occur within 24–48 hours after starting therapy5 205 206 207 267 and usually subside within 24 hours following drug discontinuance.4 90 205

Most patients respond rapidly to treatment with diazepam4 or an agent with central anticholinergic activity (e.g., diphenhydramine hydrochloride 20–50 mg orally, IM, or IV;5 267 275 276 benztropine 1–2 mg IM5 267 ).4 5 170 206 207 267

Parkinsonian symptoms (e.g., tremor, rigidity, bradykinesia, akinesia) occur rarely; may be associated with usual160 or excessive metoclopramide doses62 or decreased renal function.9 54

Possible exacerbation of parkinsonian symptoms;5 9 54 62 160 267 use with caution, if at all, in patients with parkinsonian syndrome.5 267

More common during first 6 months of therapy but occur occasionally after longer periods.5 267

Symptoms generally subside within 2–3 months following drug discontinuance.5 267

NMS (characterized by hyperthermia, varying levels of consciousness, muscular rigidity, and autonomic dysfunction) reported rarely.5 208 267

Important to determine whether untreated or inadequately treated extrapyramidal reactions and serious medical illness (e.g., pneumonia, systemic infection) may coexist.5 267 Also consider the possibility of central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, and primary CNS pathology.5 267

Immediately discontinue metoclopramide and other drugs not considered essential, provide intensive symptomatic treatment, monitor patient, and treat any concomitant serious medical condition for which specific therapies are available.5 267 Dantrolene and bromocriptine have been used in the treatment of NMS, but their efficacy has not been established and there currently is no specific drug therapy.5 267

Mild to severe depression (including suicidal ideation and suicide) has occurred in patients with or without prior history of depression.5 210 211 215 267

Use with extreme caution and only when anticipated benefits outweigh possible risks in patients with a history of mental depression, especially those with suicidal tendencies.5 267

Sensitivity Reactions

Theoretical potential for patients who are allergic to procainamide to exhibit cross-sensitivity to metoclopramide (since the drugs are structurally similar).11 12

General Precautions

When deciding whether to use metoclopramide or NG suction to prevent postoperative nausea and vomiting, consider the possibility that metoclopramide theoretically could produce increased pressure on suture lines following GI anastomosis or closure.267

Possible transient increases in plasma aldosterone concentrations and sodium retention; closely monitor patients (e.g., those with CHF or cirrhosis) at risk of developing fluid retention and volume overload or hypokalemia.3 5 69 267

Discontinue metoclopramide if fluid retention or volume overload occurs at any time during therapy.5 267

Possible increase in circulating catecholamines in hypertensive patients; use with caution in these patients.5 267

Drowsiness may occur, particularly at higher dosages.5 267 Performance of activities requiring mental alertness and physical coordination (operating machinery, driving a motor vehicle) may be impaired.5 267

Adverse reactions, particularly CNS reactions, may occur following discontinuance of drug.5 Some patients may experience withdrawal symptoms including dizziness, nervousness, and/or headaches following discontinuance.5

Patients with cytochrome-b5 reductase deficiency have an increased risk of methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered.5 267

Methylene blue is not recommended for treatment of metoclopramide-induced methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.5 267

Specific Populations

Category B.5 267

Distributed into milk.5 139 140 267 Use caution in nursing women.5 267

Manufacturers currently recommend use in children only to facilitate intubation of the small intestine;267 however, has been effective for the management of gastric stasis†178 180 181 and gastroesophageal reflux†179 182 in infants and children.

Use with caution; incidence of extrapyramidal reactions is increased in children.5 91 125 156 267

Use with caution in neonates.5 267 Neonatal susceptibility to methemoglobinemia is increased due to prolonged clearance (may cause excessive serum concentrations) in combination with decreased neonatal levels of cytochrome-b5 reductase.5 267

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.5 267

Possible increased risk of tardive dyskinesia.5 267

Risk of adverse parkinsonian effects increases with increasing dosage; administer lowest effective dosage in geriatric patients.5 267 If parkinsonian symptoms develop, generally should discontinue metoclopramide before initiating specific antiparkinsonian therapy.5 267

Confusion and oversedation may occur.5 267

Substantially eliminated by kidneys; risk of adverse reactions may be greater in patients with impaired renal function.5 267 (See Renal Impairment under Dosage and Administration.)

Select dosage with caution because of age-related decreases in renal function and concomitant disease and drug therapy.5 267 (See Geriatric Patients under Dosage and Administration).

Possible increased risk of fluid retention and hypokalemia in patients with cirrhosis.3 5 69 267 (See Fluid and Electrolyte Effects under Cautions.)

Discontinue if fluid retention or volume overload occurs at any time during therapy.5 267

Clearance may be reduced.5 54 59 142 192 267 Possible increased risk of adverse effects.5 267 Use with caution; reduce dosage during prolonged therapy in patients with renal impairment.5 54 58 59 69 135 142 267 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Restlessness, drowsiness, fatigue, lassitude, nausea, bowel disturbances (principally diarrhea).4 5 90 125 267

• Importance of providing patient or caregiver with a copy of the manufacturer’s medication guide; discuss and answer questions about its contents as needed.5 267 Importance of instructing patient or caregiver to read and understand the contents of the medication guide before initiating therapy and each time the prescription is refilled.5 267

• Importance of informing patients that metoclopramide oral solution and tablets are recommended for use in adults only.5 268 269

• Risk of tardive dyskinesia.5 267 Importance of contacting clinicians if new, abnormal, involuntary, or uncontrollable muscle movements occur (e.g., lip smacking, chewing, puckering mouth, frowning, scowling, tongue protrusion, blinking, eye movements, arm and leg shaking).5 267

• Potential for metoclopramide to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.5 267

• Potential for metoclopramide to enhance sedative effects of alcohol, barbiturates, or other CNS depressants.5 267

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.5 267

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.5 267

• Importance of informing patients of other important precautionary information.5 267 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name