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 Metoclopramide

Class:  Antiemetic Agents; Prokinetic Agents
 

Pharmacology

Mechanism of Action

Blocks dopamine receptors in chemoreceptor trigger zone of CNS and sensitizes tissues to acetylcholine; increases upper GI motility but not secretions; increases lower esophageal sphincter tone .

Absorption

Bioavailability: IM, 74-96%; PO, 65-95%
Onset: IV, 1-3 min; IM, 10-15 min; PO, 30-60 min
Duration: 1-2 hr regardless of route
Peak plasma time: IV, 15 min; PO, 60-120 min

Distribution

Protein bound: 30-40%
Vd: 3.5 L/kg

Metabolism

Metabolized by liver
Metabolites: Metoclopramide glucuronides, metoclopramide sulfates, aminoacetic acid (inactive)

Elimination

Half-life: IV/IM, 4-5 hr
Dialyzable: Not significant; dose adjustment after dialysis unnecessary
Total body clearance: 0.53-0.55 L/hr/kg (prolonged in neonates as compared with adults)
Excretion: Primarily urine (85%

Dosing & Uses

Adult

Dosing Forms & Strengths

injectable solution :5mg/mL

syrup :5mg/5mL

tablet :5mg ,10mg

Chemotherapy-Induced Nausea & Vomiting

2 mg/kg IV (infused over at least 15 minutes) 30 minutes before chemotherapy, then repeated 2 more times q2hr (after initial dose)
Vomiting suppressed: Decrease to 1 mg/kg IV q3hr for 3 doses
Vomiting not suppressed: Continue same dose q3hr for 3 doses

Diabetic Gastroparesis

10 mg IV/IM/PO q6hr 30 minutes before meals and at bedtime; use injectable dosing only if severe symptoms are present

Small Bowel Intubation/Radiologic Examination of Upper GI Tract

10 mg IV over 1-2 minutes

Gastroesophageal Reflux Disease

10-15 mg PO q6hr 30 minutes before meals and at bedtime; not to exceed 80 mg/day

Postoperative Nausea & Vomiting (Off-label)

10-20 mg IM administered near end of procedure; may be repeated postoperatively q4-6hr PRN

Pediatric

Small Bowel Intubation/Radiologic Examination of Upper GI Tract

6-14 years old: 2.5-5 mg IV over 1-2 minutes

>14 years old: 10 mg IV over 1-2 minutes

Gastroesophageal Reflux Disease (Off-label)

Neonate: 0.15 mg/kg IV q6hr 
Infant: 0.1 mg/kg IV/IM/PO q6-8hr 30 minutes before meals and at bedtime 
Not to exceed 0.3-0.75 mg/kg/day 

Diabetic Gastroparesis (Off-label)

>6 years old: 0.5 mg/kg/day PO divided q8hr

Postoperative Nausea & Vomiting (Off-label)

0.1-2 mg/kg IV q6-8hr PRN

Contraindications & Cautions

Black Box Warnings

May cause tardive dyskinesia (often irreversible)
Risk of developing tardive dyskinesia increases with treatment duration and total cumulative dose
Discontinue with signs or symptoms of tardive dyskinesia
No known treatment exists for tardive dyskinesia
Symptoms may lessen or resolve after metoclopramide treatment is stopped
Do not administer for longer than 12 weeks, except in rare cases where therapeutic benefit is thought to outweigh risk of tardive dyskinesia

Contraindications

Hypersensitivity to metoclopramide or procainamide
GI hemorrhage, mechanical obstruction, perforation, epilepsy, pheochromocytoma
Other drugs causing extrapyramidal symptoms (eg, phenothiazines, butyrophenones)

Cautions

Mental depression, parkinsonism
Suture lines after GI anastomosis or closure
Hypertension, CHF
Renal impairment, cirrhosis
Can cause tardive dyskinesia (see Black Box Warnings), especially in elderly; discontinue if signs or symptoms of tardive dyskinesia develop (metoclopramide itself may completely or partially suppress these manifestations); tardive dyskinesia may persist even after drug is discontinued
Diphenhydramine 50 mg IM can be given for extrapyramidal symptoms

Pregnancy & Lactation

Pregnancy category: B

Lactation: Drug crosses into breast milk; use caution; concern may be warranted according to American Academy of Pediatrics

Adverse Effects

10%

Extrapyramidal symptoms (dystonic reactions in 25% of young adults 18-30 years old)

1-10%

Fatigue (10%)
Restlessness (10%)
Sedation (10%)

Frequency Not Defined

Diarrhea
Nausea
Galactorrhea
Gynecomastia
Impotence
Menstrual disorders
Neuroleptic malignant syndrome
Hematologic abnormalities

SOURCE : metoclopramide