Contents

Search

metoclopramide (Reglan, Metozolv ODT)

Tradename: Reglan. Indications: 1) nausea/vomiting, including a) nausea & vomiting of pregnancy (hyperemesis gravidarum) [8,9] b) chemotherapy-induced (no better than placebo [6]) 2) gastroparesis, including diabetic & post-surgical 3) GI reflux (short-term therapy, 4-12 weeks) 4) intubation of small intestine 5) stimulation of gastric emptying following oral barium for radiographic examination of the upper GI tract Contraindication: (relative) - Parkinson's disease, Sinemet therapy Dosage: 10 mg IV/IM every 2-3 hours PRN. 10-30 mg PO QID, 30 min before meals & QHS. Tabs: 5 & 10 mg. Elixir 5 mg/5 mL (480 mL). Injection: 5 mg/mL ( 2 mL, 10 mL) Oral disintegrating tablet Metozolv ODT Pharmacokinetics: 1) onset of action a) IV: 1-3 minutes b) IM: 10-15 minutes c) PO: 30-60 minutes 2) duration of action: 1-2 hours 3) 13-30% in plasma is bound to protein, mostly albumin 4) excreted in the urine & feces 4) elimination is biphasic: a) t1/2 alpha: 5 minutes b) t1/2 beta: 2.5-6 hours 5) dose adjustment necessary with renal insufficiency Adverse effects: 1) related to dosage & duration of therapy 2) central nervous system (CNS)* a) restlessness, drowsiness, fatigue, lassitude (10%) b) insomnia, headache, dizziness, dry mouth (less frequent) c) anxiety, agitation (usually following IV infusion) d) depression e) extrapyramidal reactions 1] generally within 24-48 hours 2] usually subsides within 24 hours after drug stopped 3] more common in elderly f) acute reactions: dystonic reactions (dystonia), akasthesia g) tardive dyskinesia: [7] 1] after 1-4 years of use 2] highest incidence in elderly, especially women [5] 3] long-term therapy can cause tardive dyskinesia, limit therapy to 12 weeks [12] h) parkinsonism [10] 3) gastrointestinal (GI): nausea, diarrhea, constipation 4) hypersensitivity: a) bronchospasm b) urticaria c) maculopapular rash d) angioedema 5) increased serum prolactin a) galactorrhea b) gynecomastia c) amenorrhea 6) breast tenderness 7) cardiovascular: - hypertension, hypotension, tachycardia - risk of ischemic stroke especially in older patients & patients with dementia - greatest risk in the first month of use (RR=3.5) [11] 6) rare effects: a) agranulocytosis b) neutropenia c) leukopenia d) hepatotoxicity e) hypertensive crisis in patients with pheochromocytoma * If adverse CNS effects occur, discontinue metoclopramide. Do not attempt to simply lower the dose as the is unlikely to resolve CNS symptoms [10] Drug interactions: 1) increases the rate of absorption of alcohol 2) increases cyclosporine absorption 3) decreases digoxin absorption 4) levodopa has the opposite effect on dopamine receptors 5) succinylcholine Mechanism of action: 1) anti-emetic a) directly inhibits dopaminergic neurotransmission in the medullary chemoreceptor trigger zone (CTZ) of the area postrema b) increases lower esophageal sphincter pressure 2) dopaminergic inhibition 3) sedative 4) stimulates upper GI motility a) increases tone & amplitude of gastric contractions b) relaxes pyloric sphincter & duodenal bulb c) increases peristalsis 5) does NOT stimulate gastric, biliary or pancreatic secretions 6) lacks anesthetic & antiarrhythmic properties

Interactions

drug interactions drug adverse effects (more general classes)

General

anti-emetic benzamide dopaminergic receptor antagonist

Properties

MISC-INFO: elimination route KIDNEY 1/2life 2.5-6 HOURS pregnancy-category B + safety in lactation +

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. AHFS 96 Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1996, pg 2160
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
  6. Braude D, Soliz T, Crandall C, Hendey G, Andrews J, Weichenthal L. Antiemetics in the ED: a randomized controlled trial comparing 3 common agents. Am J Emerg Med. 2006 Mar;24(2):177-82. PMID: 16490647
  7. FDA MedWatch http://www.fda.gov/medwatch/safety/2009/safety09.htm#Metoclopramide
  8. Matok I et al, The Safety of Metoclopramide Use in the First Trimester of Pregnancy PMID: 19516033 N Engl J Med 2009 (June 11) 360:2528-2535
  9. Pasternak B et al Metoclopramide in Pregnancy and Risk of Major Congenital Malformations and Fetal Death. JAMA. 2013;310(15):1601-1611 PMID: 24129464 http://jama.jamanetwork.com/article.aspx?articleid=1752754
  10. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018
  11. Benard-Laribiere A et al. Risk of first ischaemic stroke and use of antidopaminergic antiemetics: Nationwide case-time-control study. BMJ 2022 Mar 23; 376:e066192 PMID: 35321876 Free article https://www.bmj.com/content/376/bmj-2021-066192
  12. NEJM Knowledge+

Component-of

intravenous anti-emetic combination suppository anti-emetic combination (BRD)