metoclopramide

Absorption: Well absorbed from the GI tract, from rectal mucosa, and from IM sites. 47% absorbed following intranasal administration. IV administration results in complete bioavailability.

Distribution: Widely distributed into body tissues and fluids. Crosses blood-brain barrier.

Metabolism/Excretion: Partially metabolized by the liver via the CYP2D6 isoenzyme; the CYP2D6 isoenzyme exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ metoclopramide concentrations and an ↑ risk of adverse effects). 25% eliminated unchanged in the urine.

Half-Life: 2.5–6 hr.

Time/Action Profile ⬆ ⬇

(effects on peristalsis)

ROUTE	ONSET	PEAK	DURATION
PO	30–60 min	unknown	1–2 hr
IM	10–15 min	unknown	1–2 hr
Intranasal	unknown	unknown	unknown
IV	1–3 min	immediate	1–2 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Possible GI obstruction, perforation, or hemorrhage;
Seizure disorders;
Hypertension;
Pheochromocytoma;
History of tardive dyskinesia;
Parkinson's disease;
Concurrent use of MAO inhibitors;
Moderate or severe renal or hepatic impairment (intranasal only);
CYP2D6 poor metabolizers (↑ risk for tardive dyskinesia) (intranasal only);
Concurrent use of strong CYP2D6 inhibitors (intranasal only).

Use Cautiously in:

History of depression;
Diabetes (may alter response to insulin);
Cirrhosis or HF (↑ risk of fluid retention);
Renal impairment (↓ dose in CCr <50 mL/min) (oral and IV/IM only);
Chronic use >12 wk (↑ risk for tardive dyskinesia);
Moderate or severe hepatic impairment;
CYP2D6 poor metabolizers (↑ risk for tardive dyskinesia) (oral and IV/IM only);
OB: May cause extrapyramidal symptoms or methemoglobinemia in neonate when used during pregnancy;
Lactation: May lead to diarrhea, extrapyramidal symptoms, or methemoglobinemia in infant when used during breastfeeding;
Pedi: Prolonged clearance in neonates can result in high serum concentrations and the risk for methemoglobinemia. Side effects are more common in children, especially extrapyramidal reactions. Avoid use of tablets and intranasal because of risk of tardive dyskinesia and methemoglobinemia (in neonates);
Geri: Appears on Beers list. risk of extrapyramidal effects, including tardive dyskinesia, in older adults. Avoid use in older adults, except for gastroparesis (duration for this indication should generally not exceed 12 wk). Intranasal therapy not recommended as initial therapy in older adults (can be transitioned to intranasal therapy once stabilized on oral therapy.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, hypertension, hypotension, supraventricular tachycardia

Endo: gynecomastia, hyperprolactinemia

GI: constipation, diarrhea, dry mouth, nausea

Hemat: agranulocytosis, leukopenia, methemoglobinemia, neutropenia

Neuro: drowsiness, dysgeusia (intranasal), extrapyramidal reactions, restlessness, anxiety, bradykinesia, cog-wheel rigidity, depression, irritability, NEUROLEPTIC MALIGNANT SYNDROME, tardive dyskinesia, tremor

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors may cause release of catecholamines which may ↑ BP; avoid concurrent use.
Additive CNS depression with other CNS depressants, including alcohol, antidepressants, antihistamines, opioid analgesics, and sedative/hypnotics.
May ↑ absorption and risk of toxicity from cyclosporine.
May affect the GI absorption of other orally administered drugs as a result of effect on GI motility.
May exaggerate hypotension during general anesthesia.
↑risk of tardive dyskinesia, extrapyramidal reactions, or neuroleptic malignant syndrome with antipsychotic agents; avoid concurrent use.
Strong CYP2D6 inhibitors, including bupropion, fluoxetine, paroxetine, or quinidine may ↑ levels and risk of extrapyramidal reactions; avoid concurrent use with intranasal metoclopramide; ↓ PO or IV/IM metoclopramide dose.
Opioids and anticholinergics may antagonize the GI effects of metoclopramide.
May ↑ neuromuscular blockade from succinylcholine.
May ↓ effectiveness of levodopa.
May ↑ tacrolimus serum levels.

Route/Dosage ⬆ ⬇

Prevention of Chemotherapy-Induced Nausea and Vomiting

IV (Adults and Children ): 1–2 mg/kg 30 min before chemotherapy. Additional doses of 1–2 mg/kg may be given every 2–4 hr, pretreatment with diphenhydramine will ↓ the risk of extrapyramidal reactions to this dose.

Facilitation of Small Bowel Intubation

IV (Adults and Children >14 yr): 10 mg over 1–2 min.
IV (Children 6–14 yr): 2.5–5 mg (dose should not exceed 0.5 mg/kg) over 1–2 min.
IV (Children <6 yr): 0.1 mg/kg over 1–2 min.

Diabetic Gastroparesis

PO IV IM (Adults ): 10 mg 30 min before meals and at bedtime for 2–8 wk (not to exceed 40 mg/day). CYP2D6 poor metabolizers: 5 mg 30 min before meals and at bedtime for 2–8 wk (not to exceed 20 mg/day). Concurrent use of strong CYP2D6 inhibitor: 5 mg 30 min before meals and at bedtime for 2–8 wk (not to exceed 20 mg/day).
(Adults ): One spray (15 mg) in one nostril 30 min before each meal and at bedtime (not to exceed 60 mg/day) for 2–8 wk (not to exceed 12 wk).
PO IV IM Geriatric Patients ): 5 mg 30 min before meals and at bedtime for 2–8 wk; may titrate up to 10 mg 30 min before each meal and at bedtime based on response and tolerability (not to exceed 40 mg/day).
Geriatric Patients ): Patients receiving alternative metoclopramide product at stable dose of 10 mg four times daily: One spray (15 mg) in one nostril 30 min before each meal and at bedtime (not to exceed 60 mg/day) for 2–8 wk (not to exceed 12 wk).

Renal Impairment

PO (Adults ): CCr ≤60 mL/min: 5 mg 30 min before meals and at bedtime for 2–8 wk (not to exceed 20 mg/day). End-stage renal disease (including hemodialysis and peritoneal dialysis): 5 mg twice daily for 2–8 wk (not to exceed 10 mg/day).

Hepatic Impairment

PO IV IM (Adults ): Mild hepatic impairment: 10 mg 30 min before meals and at bedtime for 2–8 wk (not to exceed 40 mg/day). Moderate or severe hepatic impairment: 5 mg 30 min before meals and at bedtime for 2–8 wk (not to exceed 20 mg/day).

Gastroesophageal Reflux

PO (Adults ): 10–15 mg 30 min before each meal and at bedtime (not to exceed 60 mg/day). CYP2D6 poor metabolizers: 5 mg 30 min before each meal and at bedtime or 10 mg 3 times daily (not to exceed 30 mg/day). Concurrent use of strong CYP2D6 inhibitor: 5 mg 30 min before each meal and at bedtime or 10 mg 3 times daily (not to exceed 30 mg/day).
PO Geriatric Patients ): 5 mg 30 min before each meal and at bedtime; may titrate up to 10–15 mg 30 min before each meal and at bedtime based on response and tolerability (not to exceed 60 mg/day).

Renal Impairment

PO (Adults ): CCr ≤60 mL/min: 5 mg 30 min before each meal and at bedtime or 10 mg 3 times daily (not to exceed 30 mg/day). End-stage renal disease (including hemodialysis and peritoneal dialysis): 5 mg 30 min before each meal and at bedtime or 10 mg twice daily (not to exceed 20 mg/day).

Hepatic Impairment

PO (Adults ): Mild hepatic impairment: 10–15 mg 30 min before each meal and at bedtime (not to exceed 60 mg/day). Moderate or severe hepatic impairment: 5 mg 30 min before each meal and at bedtime or 10 mg 3 times daily (not to exceed 30 mg/day).

Prevention of Postoperative Nausea and Vomiting

IM IV (Adults ): 10 mg at the end of surgical procedure, repeat in 6–8 hr if needed.

Treatment of Hiccups

PO IM (Adults ): 10–20 mg 4 times daily PO; may be preceded by a single 10-mg dose IM.

Availability ⬆ ⬇

(Generic available)

Tablets: 5 mg; 10 mg
Orally disintegrating tablets: 5 mg; 10 mg
Oral solutionapricot-peach flavor: 5 mg/5 mL
Nasal spray: 15 mg/metered spray in 9.8–mL bottle (delivers 112 metered sprays)
Solution for injection: 5 mg/mL

Assessment ⬆ ⬇

Assess for nausea, vomiting, abdominal distention, and bowel sounds before and after administration.
Assess for extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling, mask-like face, shuffling gait, rigidity, tremors; and dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) periodically throughout course of therapy. May occur wk to mo after initiation of therapy and are reversible on discontinuation. Dystonic reactions may occur within min of IV infusion and stop within 24 hr of discontinuation of metoclopramide. May be treated with 50 mg of IM diphenhydramine or diphenhydramine 1 mg/kg IV may be administered prophylactically 15 min before metoclopramide IV infusion.
Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Avoid treatment with metoclopramide (all dose forms and routes of administration) for longer than 12 wk due to increased risk of developing tardive dyskinesia with longer-term use. Report immediately and discontinue metoclopramide; may be irreversible.
Monitor for neuroleptic malignant syndrome (hyperthermia, muscle rigidity, altered consciousness, irregular pulse or BP, tachycardia, and diaphoresis). Report immediately.
Assess for signs of depression periodically throughout therapy.
Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).

Lab Test Considerations:

May alter hepatic function test results.
- May cause ↑ serum prolactin and aldosterone concentrations.

Implementation ⬆ ⬇

PO: Administer doses 30 min before meals and at bedtime.
- Do not remove orally disintegrating tablets from the bottle until just prior to dosing. Remove tablet from bottle with dry hands and immediately place on tongue to disintegrate and swallow with saliva. Tablet typically disintegrates in 1–1.5 min. Administration with liquid is not necessary.
IM: For prevention of postoperative nausea and vomiting, inject IM near the end of surgery.
Administer 1 spray in one nostril. Before administering 1st dose from a bottle, prime the pump by pressing down on the finger flange and releasing 10 sprays in the air. Place the spray nozzle tip under one nostril and lean the head slightly forward so the tip of spray nozzle is aimed away from the septum and toward the back of the nose. Close the other nostril with the other index finger. Move spray pump upwards so the tip of the nozzle is in the nostril. To ensure a full dose, hold the bottle upright while pressing down firmly and completely on finger flange and release while inhaling slowly through the open nostril. Remove spray pump nozzle tip from nostril and exhale slowly through the mouth. Wipe the spray nozzle with a clean tissue. If uncertain that spray entered the nose, do not repeat dose. Take next dose at scheduled time.

IV Administration:

Administer IV dose 30 min before administration of chemotherapeutic agent.
Rate: Doses may be given slowly over 1–2 min. Rapid administration causes a transient but intense feeling of anxiety and restlessness followed by drowsiness.
Intermittent Infusion: Diluent: May be diluted for IV infusion in 50 mL of D5W, 0.9% NaCl, D5/0.45% NaCl, Ringer’s solution, or LR. Diluted solution is stable for 48 hr if protected from light or 24 hr under normal light.Concentration: May dilute to 0.2 mg/mL or give undiluted at 5 mg/mL.
Rate: Infuse slowly (maximum rate 5 mg/min) over at least 15–30 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take metoclopramide as directed. Explain how to administer intranasal doses. Take oral missed doses as soon as remembered if not almost time for next dose. If an intranasal dose is missed, omit and take the next dose at regularly scheduled time; do not double doses. Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
Pedi: Unintentional overdose has been reported in infants and children with the use of metoclopramide oral solution. Teach parents how to accurately read labels and administer medication.
May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to avoid concurrent use of alcohol and other CNS depressants while taking this medication.
Inform patient of risk of extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome. Advise patient to notify health care professional immediately if involuntary or repetitive movements of eyes, face, or limbs occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Monitor neonates for extrapyramidal signs and methemoglobinemia.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇