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Medication Safety Issues

Sound-alike/look-alike issues:

Metoclopramide may be confused with metolazone

Reglan® may be confused with Megace®, Regonol®, Renagel®

Pronunciation

(met oh KLOE pra mide)

U.S. Brand Names

• Reglan®

Generic Available

Yes

Canadian Brand Names

• Apo-Metoclop®
• Metoclopramide Hydrochloride Injection
• Nu-Metoclopramide

Pharmacologic Category

• Antiemetic
• Gastrointestinal Agent, Prokinetic

Pharmacologic Category Synonyms

• Prokinetic Gastrointestinal Agent

Use: Labeled Indications

Oral: Symptomatic treatment of diabetic gastric stasis; gastroesophageal reflux

I.V., I.M.: Symptomatic treatment of diabetic gastric stasis; postpyloric placement of enteral feeding tubes; prevention and/or treatment of nausea and vomiting associated with chemotherapy, or postsurgery; to stimulate gastric emptying and intestinal transit of barium during radiological examination

Pregnancy Risk Factor

B

Pregnancy Considerations

Crosses the placenta; available evidence suggests safe use during pregnancy.

Lactation

Enters breast milk/use caution

Breast-Feeding Considerations

Enters breast milk; may increase milk production

Contraindications

Hypersensitivity to metoclopramide or any component of the formulation; GI obstruction, perforation or hemorrhage; pheochromocytoma; history of seizures

Warnings/Precautions

Concerns related to adverse effects:

• Depression: Mental depression has occurred, symptoms range from mild to severe (suicidal ideation and suicide); use with caution in patients with a history of mental illness.

• Extrapyramidal symptoms (EPS): May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is higher in pediatric patients and adults <30 years of age). Typically occurs within the initial 24-48 hours of treatment; risk is increased at higher dosages. Use caution with concurrent use of other drugs associated with EPS.

• Neuroleptic malignant syndrome (NMS): Use may be associated (rarely) with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity and/or autonomic instability.

Disease-related concerns:

• Edematous conditions: Use with caution in patients who are at risk of fluid overload (HF, cirrhosis). May cause transient increase in serum aldosterone; use lowest recommended doses initially.

• Hypertension: Use with caution in patients with hypertension.

• NADH-cytochrome b5 reductase deficiency: Patients with NADH-cytochrome b5 reductase deficiency are at increased risk of methemoglobinemia and/or sulfhemoglobinemia.

• Parkinson's disease: Use with caution in patients with parkinson's disease; may have increased risk of tardive dyskinesia.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be needed.

• Surgical anastomosis/closure: Use with caution following surgical anastomosis/closure; promotility agents may theoretically increase pressure in suture lines.

Special populations:

• Elderly: Use with caution in the elderly; may have increased risk of tardive dyskinesia.

Other warnings/precautions:

• Discontinuation of therapy: Abrupt discontinuation may (rarely) result in withdrawal symptoms (dizziness, headache, nervousness).

Adverse Reactions

Frequency not always defined.

Cardiovascular: AV block, bradycardia, CHF, fluid retention, flushing (following high I.V. doses), hyper-/hypotension, supraventricular tachycardia

Central nervous system: Drowsiness (~10% to 70%; dose related), fatigue (~10%), restlessness (~10%), acute dystonic reactions (<1% to 25%; dose and age related), akathisia, confusion, depression, dizziness, hallucinations (rare), headache, insomnia, neuroleptic malignant syndrome (rare), Parkinsonian-like symptoms, suicidal ideation, seizure, tardive dyskinesia

Dermatologic: Angioneurotic edema (rare), rash, urticaria

Endocrine & metabolic: Amenorrhea, galactorrhea, gynecomastia, impotence

Gastrointestinal: Diarrhea, nausea

Genitourinary: Incontinence, urinary frequency

Hematologic: Agranulocytosis, leukopenia, neutropenia, porphyria

Hepatic: Hepatotoxicity (rare)

Ocular: Visual disturbance

Respiratory: Bronchospasm, laryngeal edema (rare)

Miscellaneous: Allergic reactions, methemoglobinemia, sulfhemoglobinemia

Metabolism/Transport Effects

Substrate (minor) of CYP1A2, 2D6; Inhibits CYP2D6 (weak)

Drug Interactions

Anti-Parkinson 's Agents (Dopamine Agonist): Metoclopramide may diminish the therapeutic effect of Anti-Parkinson 's Agents (Dopamine Agonist). Risk C: Monitor therapy

CycloSPORINE: Metoclopramide may increase the absorption of CycloSPORINE. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (may increase CNS depression).

Storage

Injection: Store intact vial at controlled room temperature; injection is photosensitive and should be protected from light during storage; parenteral admixtures in D₅W or NS are stable for at least 24 hours and do not require light protection if used within 24 hours.

Tablet: Store at controlled room temperature.

Compatibility

Stable in D₅1/2NS, D₅W, mannitol 20%, LR, NS; variable stability (consult detailed reference) in TPN.

Y-site administration: Compatible: Acyclovir, aldesleukin, amifostine, aztreonam, bleomycin, ciprofloxacin, cisatracurium, cisplatin, cladribine, clarithromycin, cyclophosphamide, cytarabine, diltiazem, docetaxel, doxorubicin, droperidol, etoposide phosphate, famotidine, filgrastim, fluconazole, fludarabine, fluorouracil, foscarnet, gatifloxacin, gemcitabine, granisetron, heparin, idarubicin, leucovorin, levofloxacin, linezolid, melphalan, meperidine, meropenem, methotrexate, mitomycin, morphine, ondansetron, paclitaxel, piperacillin/tazobactam, remifentanil, sargramostim, sufentanil, tacrolimus, teniposide, thiotepa, topotecan, vinblastine, vincristine, vinorelbine, zidovudine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, amsacrine, cefepime, doxorubicin liposome, furosemide, propofol. Variable (consult detailed reference): TPN.

Compatibility in syringe: Compatible: Aminophylline, ascorbic acid injection, atropine, benztropine, bleomycin, butorphanol, chlorpromazine, cisplatin, cyclophosphamide, cytarabine, dexamethasone sodium phosphate, diamorphine, dimenhydrinate, diphenhydramine, doxorubicin, droperidol, fentanyl, fluorouracil, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydroxyzine, insulin (regular), leucovorin, lidocaine, magnesium sulfate, meperidine, methotrimeprazine, methylprednisolone sodium succinate, midazolam, mitomycin, morphine, ondansetron, pentazocine, perphenazine, prochlorperazine edisylate, promazine, promethazine, ranitidine, scopolamine, sufentanil, vinblastine, vincristine, vitamin B complex with C. Incompatible: Ampicillin, calcium gluconate, chloramphenicol, furosemide, penicillin G potassium, sodium bicarbonate. Variable (consult detailed reference): Methotrexate.

Compatibility when admixed: Compatible: Cimetidine, clindamycin, diamorphine, meperidine, meropenem, morphine, multivitamins, potassium acetate, potassium chloride, potassium phosphate, verapamil. Incompatible: Dexamethasone sodium phosphate with lorazepam and diphenhydramine, erythromycin lactobionate, floxacillin, fluorouracil, furosemide.

Mechanism of Action

Blocks dopamine receptors and (when given in higher doses) also blocks serotonin receptors in chemoreceptor trigger zone of the CNS; enhances the response to acetylcholine of tissue in upper GI tract causing enhanced motility and accelerated gastric emptying without stimulating gastric, biliary, or pancreatic secretions; increases lower esophageal sphincter tone

Pharmacodynamics/Kinetics

Onset of action: Oral: 0.5-1 hour; I.V.: 1-3 minutes; I.M.: 10-15 minutes

Duration: Therapeutic: 1-2 hours, regardless of route

Distribution: V_d: 2-4 L/kg

Protein binding: 30%

Bioavailability: Oral: 65% to 95%

Half-life elimination: Normal renal function: 4-6 hours (may be dose dependent)

Time to peak, serum: Oral: 1-2 hours

Excretion: Urine (~85%)

Dosage

Children:

Gastroesophageal reflux (unlabeled use): Oral: 0.1-0.2 mg/kg/dose 4 times/day

Antiemetic (chemotherapy-induced emesis) (unlabeled): I.V.: 1-2 mg/kg 30 minutes before chemotherapy and every 2-4 hours

Postpyloric feeding tube placement: I.V.:

<6 years: 0.1 mg/kg

6-14 years: 2.5-5 mg

>14 years: Refer to adult dosing.

Adults:

Gastroesophageal reflux: Oral: 10-15 mg/dose up to 4 times/day 30 minutes before meals or food and at bedtime; single doses of 20 mg are occasionally needed for provoking situations. Treatment >12 weeks has not been evaluated.

Diabetic gastric stasis:

Oral: 10 mg 30 minutes before each meal and at bedtime

I.M., I.V. (for severe symptoms): 10 mg over 1-2 minutes; 10 days of I.V. therapy may be necessary for best response

Chemotherapy-induced emesis:

I.V.: 1-2 mg/kg 30 minutes before chemotherapy and repeated every 2 hours for 2 doses, then every 3 hours for 3 doses (manufacturer labeling)

Alternate dosing (with or without diphenhydramine):

Moderate emetic risk chemotherapy: 0.5 mg/kg every 6 hours on days 2-4

Low and minimal risk chemotherapy: 1-2 mg/kg every 3-4 hours

Breakthrough treatment: 1-2 mg/kg every 3-4 hours

Oral (unlabeled use; with or without diphenhydramine):

Moderate emetic risk chemotherapy: 0.5 mg/kg every 6 hours or 20 mg 4 times/day on days 2-4

Low and minimal risk chemotherapy: 20-40 mg every 4-6 hours

Breakthrough treatment: 20-40 mg every 4-6 hours

Postoperative nausea and vomiting: I.M., I.V.: 10-20 mg near end of surgery

Postpyloric feeding tube placement, radiological exam: I.V.: 10 mg

Elderly:

Gastroesophageal reflux: Oral: 5 mg 4 times/day (30 minutes before meals or food and at bedtime); increase dose to 10 mg 4 times/day if no response at lower dose

Gastrointestinal hypomotility:

Oral: Initial: 5 mg 30 minutes before meals and at bedtime; increase if necessary to 10 mg doses

I.V.: Initiate at 5 mg over 1-2 minutes; increase to 10 mg if necessary

Postoperative nausea and vomiting: I.M., I.V.: 5 mg near end of surgery; may repeat dose if necessary

Dosing adjustment in renal impairment: Cl_cr <40 mL/minute: Administer at 50% of normal dose

Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary

Administration: I.M.

May be administered I.M.

Administration: I.V.

Injection solution may be given I.M., direct I.V. push, short infusion (15-30 minutes), or continuous infusion; lower doses (?10 mg) of metoclopramide can be given I.V. push undiluted over 1-2 minutes; higher doses to be given IVPB over at least 15 minutes; continuous SubQ infusion and rectal administration have been reported. Note: Rapid I.V. administration may be associated with a transient (but intense) feeling of anxiety and restlessness, followed by drowsiness.

Administration: Other

Continuous SubQ infusion and rectal administration have been reported

Administration: I.V. Detail

pH: 3.0-6.5

Monitoring Parameters

Dystonic reactions; signs of hypoglycemia in patients using insulin and those being treated for gastroparesis; agitation, and onfusion

Test Interactions

Increased aminotransferase [ALT/AST] (S), increased amylase (S)

Patient Education

Do not take any new medication during therapy unless approved by prescriber. Oral: Take this drug as prescribed, 30 minutes prior to eating. Do not increase dosage. Avoid alcohol; may increase adverse effects. May cause dizziness, drowsiness, or blurred vision (use caution when driving or engaging in tasks that require alertness until response to drug is known); cause restlessness, anxiety, depression, or insomnia (will reverse when medication is discontinued). Report any CNS changes, spasticity or involuntary movements, unresolved diarrhea, fluid retention (swelling of extremities, weight gain); visual disturbances; palpitations or rapid heart beat; or any other persistent adverse effects. Breast-feeding precaution: Breast-feeding is not recommended.

Geriatric Considerations

Elderly are more likely to develop tardive dyskinesia syndrome (especially elderly females) reactions than younger adults. Use lowest recommended doses initially. Must consider renal function (estimate creatinine clearance). It is recommended to do involuntary movement assessments on elderly using this medication at high doses and for long-term therapy.

Anesthesia and Critical Care Concerns/Other Considerations

The consensus guidelines for postoperative nausea and vomiting (Gan, 2003) does not recommend the use of metoclopramide.

Cardiovascular Considerations

Metoclopramide dose not cause QT prolongation.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Drowsiness and restlessness are common; may cause insomnia or depression. Depression has occurred in patients with and without a prior history of depression. Symptoms have ranged from mild to severe, and have included suicidal ideation and suicide. Metoclopramide is a D₂ blocker; may cause extrapyramidal symptoms especially when used in high dosages (dystonia) or in the elderly (tardive dyskinesia). Dystonic reactions occur in approximately 1 in 500 patients with the usual adult dosage of 30-40 mg/day. These reactions are usually seen during the first 1-2 days of therapy with metoclopramide, occurring more frequently in pediatric patients and adults <30 years of age, and are more frequent when higher doses are used in prophylaxis of vomiting due to cancer chemotherapy. NMS has rarely been reported.

Mental Health: Effects on Psychiatric Treatment

Anticholinergics may antagonize metoclopramide's effects; concurrent use with psychotropic may produce additive sedation

Nursing: Physical Assessment/Monitoring

Assess potential for interactions with other pharmacological agents patient may be taking (eg, any antipsychotic agents, opioids, anticholinergics). Vital signs should be monitored during intravenous administration. Inpatients should use safety measures (eg, side rails up, call light within reach) and caution patient to call for assistance with ambulation. Assess results of laboratory tests (periodic renal function tests), therapeutic effectiveness (relief of symptoms), and adverse reactions (eg, extrapyramidal effects, parkinsonian-like reactions, seizures, fluid retention, adverse CNS changes). Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report (eg, CNS restlessness, drowsiness, depression, rash).

Oncology: Emetic Potential

Very low (<10%)

Oncology: Vesicant

No

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution [preservative free]: 5 mg/mL (2 mL)

Reglan®: 5 mg/mL (2 mL, 10 mL, 30 mL)

Solution, oral: 5 mg/5 mL (10 mL, 480 mL)

Tablet: 5 mg, 10 mg

Reglan®: 5 mg, 10 mg

Pricing: U.S. (www.drugstore.com)

Solution (Metoclopramide HCl)

5 mg/5 mL (240): $15.99

Tablets (Metoclopramide HCl)

5 mg (30): $12.99

10 mg (90): $15.99

Tablets (Reglan)

5 mg (30): $32.99

10 mg (30): $54.99

References

“American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.

Bruera E, Seifert L, Watanabe S, et al, "Chronic Nausea in Advanced Cancer Patients: A Retrospective Assessment of a Metoclopramide-Based Antiemetic Regimen," J Pain Symptom Manage, 1996, 11(3):147-53.

Desmond PV and Watson KJ, "Metoclopramide - A Review," Med J Aust, 1986, 144(7):366-9.

DiPalma JR, “Metoclopramide: A Dopamine Receptor Antagonist,” Am Fam Physician, 1990, 41(3):919-24.

Gan TJ, Meyer T, Apfel CC, et al, “Consensus Guidelines for Managing Postoperative Nausea and Vomiting,” Anesth Analg, 2003, 97(1):62-71.

Harrington RA, Hamilton CW, Brogden RN, et al, “Metoclopramide. An Updated Review of Its Pharmacological Properties and Clinical Use,” Drugs, 1983, 25(5):451-94.

Hart J, "Pediatric Gastroesophageal Reflux," Am Fam Physician, 1996, 54(8):2463-72.

Karadsheh NS, Shaker Q, and Ratroat B, “Metoclopramide-induced Methemoglobinemia in a Patient With Co-Existing Deficiency of Glucose-6-Phosphate Dehydrogenase and NADH-Cytochrome b5 Reductase: Failure of Methylene Blue Treatment,” Haematologica, 2001, 86(6):659-60.

Mary AM and Bhupalam L, “Metoclopramide-induced Methemoglobinemia in an Adult,” J KY Med Assoc, 2000, 98(6):245-7.

McGovern EM, Grevel J, and Bryson SM, "Pharmacokinetics of High-Dose Metoclopramide in Cancer Patients," Clin Pharmacokinet, 1986, 11(6):415-24.

National Comprehensive Cancer Network (NCCN), “Clinical Practice Guidelines in Oncology™: Antiemesis,” Version 1, 2008. Available at http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf.

Parrish RH and Bonzo SM, “Use of Metoclopramide Suppositories,” Clin Pharm, 1983, 2:395-6.

Patterson JF, “Neuroleptic Malignant Syndrome Associated With Metoclopramide,” South Med J, 1988, 81(5):674-5.

Schulze-Delrieu K, “Drug Therapy. Metoclopramide,” N Engl J Med, 1981, 305(1):28-33.

Van Veldhuizen PJ and Wyatt A, “Metoclopramide-induced Sulfhemoglobinemia,” Am J Gastroenterol, 1995, 90(6):1010-1.

International Brand Names

• Afipran (NO)
• Ametic (ZA)
• Biclomet (PH)
• Bondigest (CO)
• Carnotprim (MX)
• Cerucal (DE, EE, HU, PL)
• Clopamon (ZA)
• Clopan (IT)
• Clopram (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
• Dart (BR)
• Dibertil (BE, LU, RU)
• Dirpasid (MX)
• Emetal (TH)
• Emetic (BR)
• Emperal (BG, DK)
• Enzimar (CO)
• Gastro-Timelets (LU)
• Gastrobi (KP)
• Gastrolon (MY)
• Gastronerton (DE, LU)
• Gastrosil (CH, DE, LU, PL, RU)
• Gavistal (ID)
• Gensil (TH)
• Hemesys (PE)
• Imperan (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
• Itan (CN)
• Legir (UY)
• Macperan (KP)
• Manosil (TH)
• Maril (HK, TH)
• Martomide (HK)
• Maxeron (IN)
• Maxolon (AE, AU, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GB, GH, GM, GN, GY, HK, IE, IL, IQ, IR, JM, JO, KE, KP, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW)
• MCP-Beta Tropfen (DE)
• MCP-ratiopharm (LU)
• Meclomid (MX)
• Metamide (NZ)
• Metlazel (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
• Metoclamid (LU)
• Metoclopramid (PL)
• Metoclopramide-Eurogenerics (LU)
• Metoclopramidum (PL)
• Metoclor (TH)
• Metocobil (IT)
• Metocyl (MY)
• Metolon (MY)
• Metopram (FI)
• Movistal (LU)
• Nausil (TH)
• Nilatika (ID)
• Normastin (ID)
• Paspertin (HU)
• Perinorm (IN, ZA)
• Perone (TW)
• Pharmyork (GR)
• Plasil (AE, BF, BH, BJ, CI, CO, CY, EG, ET, GH, GM, GN, ID, IL, IQ, IR, IT, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, NE, NG, OM, PH, PY, QA, SA, SC, SD, SL, SN, SY, TH, TN, TZ, UG, YE, ZA, ZM, ZW)
• Polcotec (MX)
• Pramidin (PL)
• Pramin (AU, IL)
• Primperan (AT, BE, BF, BG, BJ, CH, CI, CO, CZ, DE, DK, EC, ES, ET, FI, FR, GB, GH, GM, GN, GR, HK, HN, IE, IT, JP, KE, LR, LU, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, PE, PT, RU, SC, SD, SE, SL, SN, TN, TR, TW, TZ, UG, VE, ZA, ZM, ZW)
• Primperil (AR)
• Prinparl (JP)
• Prokinyl (LU)
• Prowel (TW)
• Pulin (MY, SG)
• Regelan (PK)
• Reglan (HR, IN)
• Reglomar (PH)
• Reliveran (AR)
• Setin (ZA)
• Sotatic-10 (ID)
• Vertivom (ID)
• Zumatrol (ID)

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Last full review/revision August 2008

Content last modified August 2008