metoclopramide (Rx)

>10%

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

1-10%

Fatigue (2-10%)

Restlessness (10%)

Sedation (10%)

Headache (4-5%)

Dizziness (1-4%)

Somnolence (2-3%)

Frequency Not Defined

Diarrhea

Nausea

Galactorrhea

Gynecomastia

Impotence

Menstrual disorders

Neuroleptic malignant syndrome

Hematologic abnormalities

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

History of tardive dyskinesia (TD) or a dystonic reaction to metoclopramide

When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation)

Presence of pheochromocytoma or other catecholamine-releasing paragangliomas

Patients with history of epilepsy

Other drugs causing extrapyramidal symptoms (eg, phenothiazines, butyrophenones)

Cautions

Mental depression reported; use with caution in patients with history of mental illness

Use with caution or avoid in parkinson disease patients; may have increased risk of extrapyramidal symptoms

Use with caution after GI anastomosis or closure; promotility agents reported to increase pressure in suture lines

Use caution in patients with hypertension, CHF, renal impairment, cirrhosis

Use caution in patients who are at risk of fluid overload

Metoclopramide may cause a potentially fatal symptom complex called neuroleptic malignant syndrome (NMS). NMS has been reported in association with metoclopramide overdosage and concomitant treatment with another drug associated with NMS; discontinue therapy immediately if symptoms occur

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

As with other dopamine D2 receptor antagonists, metoclopramide elevates prolactin levels

Galactorrhea, amenorrhea, gynecomastia, and impotence reported with prolactin-elevating drugs, including metoclopramide; hyperprolactinemia may potentially stimulate prolactin-dependent breast cancer; however, some clinical studies and epidemiology studies have not shown an association between administration of dopamine D2 receptor antagonists and tumorigenesis in humans

May impair mental and/or physical abilities required for performance of hazardous tasks such as operating machinery or driving a motor vehicle; concomitant use of central nervous system (CNS) depressants or drugs associated with EPS may increase this effect (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics); avoid drug or the interacting drug, depending on importance of drug to the patient

Diphenhydramine 50 mg IM can be given for extrapyramidal symptoms

Pseudoparkisonism (eg, tremor, rigidity) may occur within 6 months of therapy; reversible within 2-3 months of discontinuing therapy

Metoclopramide IV administration associated with catecholamine release; use caution in patients with hypertension

Hypertensive crisis reported in patients with undiagnosed pheochromocytoma; discontinue therapy immediately with any sudden increase in blood pressure during therapy

May cause QT prolongation and torsades de pointes in some patients with heart failure patients that also have renal impairment; data on healthy males have failed to show similar effects; implicatiosn unclear; use caution in cardiovascular disease

Pregnancy

Published studies, including retrospective cohort studies, national registry studies, and meta-analyses, do not report an increased risk of adverse pregnancy-related outcomes with use of metoclopramide during pregnancy. There are potential risks to neonate following exposure in utero to metoclopramide during delivery; in animal reproduction studies, no adverse developmental effects were observed with oral administration of metoclopramide to pregnant rats and rabbits at exposures about 6 and 12 times the maximum recommended human dose (MRHD)

Metoclopramide crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery; monitor neonates for extrapyramidal signs

Lactation

Limited published data report the presence of metoclopramide in human milk in variable amounts; breastfed infants exposed to metoclopramide have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation; metoclopramide elevates prolactin levels; however, published data are not adequate to support drug effects on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Monitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia

Mechanism of Action

Blocks dopamine receptors (at high dose) and serotonin 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: 1-3 min (IV, ); 10-15 min (IM); 30-60 min (PO)

Duration: 1-2 hr regardless of route

Peak serum 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): 5-6hr (adults); 4 hr (children)

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%)

IV Incompatibilities

Solution: D5W (at high drug concentration)

Additive: Dexamethasone sodium phosphate with lorazepam and diphenhydramine, erythromycin lactobionate, floxacillin, fluorouracil, furosemide

Syringe: Ampicillin, calcium gluconate, chloramphenicol sodium succinate, furosemide, methotrexate, penicillin G potassium, sodium bicarbonate

Y-site: Allopurinol, amphotericin B cholesteryl sulfate, amsacrine, cefepime, doxorubicin liposomal, furosemide, propofol

IV Compatibilities

Additive: Cimetidine, clindamycin, meperidine, meropenem, morphine sulphate, potassium chloride, verapamil

Syringe (partial list): Butorphanol, chlorpromazine, cisplatin, cyclophosphamide, cytarabine, dexamethasone, dimenhydrinate, diphenhydramine, doxorubicin, fentanyl, fentanyl with midazolam, fluorouracil, heparin, hydromorphone, hydroxyzine, insulin, lidocaine, magnesium sulfate, meperidine, midazolam, morphine, ondansetron, pentazocine, prochlorperazine, promethazine, ranitidine, vitamins B and C

Y-site (partial list): Aztreonam, bivalirudin, ciprofloxacin, cisplatin, cytarabine, diltiazem, docetaxel, doxorubicin, famotidine, fentanyl, fluconazole, fluorouracil, heparin, hydromorphone, linezolid, meperidine, morphine sulfate, ondansetron, quinupristin-dalfopristin, zidovudine

IV Administration

NS is preferred diluent because drug is most stable in this solution

Dose ≤10 mg: IV push over 1-2 minutes

Dose >10 mg: Dilute in 50 mL D5W or NS, and infuse over at least 15 minutes

Protect from light