metoclopramide (Reglan, Metozolv ODT)

Introduction

Tradename: Reglan.

Indications

• nausea/vomiting, including
  • nausea & vomiting of pregnancy (hyperemesis gravidarum)
  • chemotherapy-induced (no better than placebo)
• gastroparesis, including diabetic & post-surgical
• GI reflux (short-term therapy, 4-12 weeks)
• intubation of small intestine
• stimulation of gastric emptying following oral barium for radiographic examination of the upper GI tract

Contraindications

(relative)

• Parkinson's disease, Sinemet therapy

pregnancy category = b

pregnancy category = +

safety in lactation = +

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

• onset of action
  • IV: 1-3 minutes
  • IM: 10-15 minutes
  • PO: 30-60 minutes
• duration of action: 1-2 hours
• 13-30% in plasma is bound to protein, mostly albumin
• excreted in the urine & feces
• elimination is biphasic:
  • t1/2 alpha: 5 minutes
  • t1/2 beta: 2.5-6 hours
• dose adjustment necessary with renal insufficiency

elimination via kidney

1/2life = 2.5-6 hours

Adverse effects

• related to dosage & duration of therapy
• central nervous system (CNS)*
  • restlessness, drowsiness, fatigue, lassitude (10%)
  • insomnia, headache, dizziness, dry mouth (less frequent)
  • anxiety, agitation (usually following IV infusion)
  • depression
  • extrapyramidal reactions
    • generally within 24-48 hours
    • usually subsides within 24 hours after drug stopped
    • more common in elderly
  • acute reactions: dystonic reactions (dystonia), akasthesia
  • tardive dyskinesia:
    • after 1-4 years of use
    • highest incidence in elderly, especially women
    • long-term therapy can cause tardive dyskinesia, limit therapy to 12 weeks
  • parkinsonism
• gastrointestinal (GI): nausea, diarrhea, constipation
• hypersensitivity:
  • bronchospasm
  • urticaria
  • maculopapular rash
  • angioedema
• increased serum prolactin
  • galactorrhea
  • gynecomastia
  • amenorrhea
• breast tenderness
• 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)
• rare effects:
  • agranulocytosis
  • neutropenia
  • leukopenia
  • hepatotoxicity
  • 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

• drug adverse effects of dopaminergic receptor antagonists
• drug adverse effects of antihypertensive agents

Drug interactions

• increases the rate of absorption of alcohol
• increases cyclosporine absorption
• decreases digoxin absorption
• levodopa has the opposite effect on dopamine receptors
• succinylcholine

• drug interaction(s) of NSAIDs & antihypertensives

Mechanism of action

• anti-emetic
  • directly inhibits dopaminergic neurotransmission in the medullary chemoreceptor trigger zone (CTZ) of the area postrema
  • increases lower esophageal sphincter pressure
• dopaminergic inhibition
• sedative
• stimulates upper GI motility
  • increases tone & amplitude of gastric contractions
  • relaxes pyloric sphincter & duodenal bulb
  • increases peristalsis
• does NOT stimulate gastric, biliary or pancreatic secretions
• lacks anesthetic & antiarrhythmic properties

More general terms

• benzamide
• dopaminergic receptor antagonist
• anti-emetic

Component of

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

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4168
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=23659
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656838
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=657384