Metoclopramide (nasal)

Antipsychotics : Potential for additive effects, including TD, EPS, and NMS; avoid concomitant use. ( 7.1 ) Central nervous system (CNS) depressants : Increased risk of CNS depression. Avoid concomitant use and monitor for adverse reactions. ( 7.1 ) Monoamine oxidase (MAO) inhibitors : Increased risk of hypertension; avoid concomitant use. ( 5.5 , 7.1 ) Additional drug interactions : See Full Prescribing Information. ( 7.1 , 7.2 )

7.1 Effects of Other Drugs on Metoclopramide Table 1 displays the effects of other drugs on metoclopramide. Table 1. Effects of Other Drugs on Metoclopramide Antipsychotics Clinical Impact Potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Intervention Avoid concomitant use [see Warnings and Precautions ( 5.1 , 5.2 , 5.3) ]. Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category Above Clinical Impact Increased plasma concentrations of metoclopramide; risk of exacerbation of extrapyramidal symptoms [see Clinical Pharmacology ( 12.3 )].

Intervention Use of GIMOTI is not recommended [see Warnings and Precautions ( 5.9 )] . Examples quinidine, bupropion, fluoxetine, and paroxetine Monoamine Oxidase Inhibitors Clinical Impact Increased risk of hypertension [see Warnings and Precautions ( 5.5 )]. Intervention Avoid concomitant use. Central Nervous System (CNS) Depressants Clinical Impact Increased risk of CNS depression [see Warnings and Precautions ( 5.8 )]. Intervention Avoid GIMOTI or the interacting drug, depending on the importance of the drug to the patient.

Examples alcohol, sedatives, hypnotics, opiates, and anxiolytics Drugs that Impair Gastrointestinal Motility Clinical Impact Potential for decreased effect of metoclopramide due to opposing effects on gastrointestinal motility. Intervention Monitor for reduced effect on gastrointestinal motility. Examples antiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiates Dopaminergic Agonists and Other Drugs that Increase Dopamine Concentrations Clinical Impact Decreased therapeutic effect of metoclopramide due to opposing effects on dopamine. Intervention Monitor for reduced therapeutic effect.

Examples apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine

7.2 Effects of Metoclopramide on Other Drugs Table 2 displays the effects of metoclopramide on other drugs. Table 2. Effects of Metoclopramide on Other Drugs Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations Clinical Impact Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms). Intervention Avoid concomitant use [see Warnings and Precautions ( 5.2 )] . Examples Apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotine Succinylcholine, Mivacurium Clinical Impact Metoclopramide inhibits plasma cholinesterase leading to enhanced neuromuscular blockade.

Intervention Monitor for signs and symptoms of prolonged neuromuscular blockade Drugs with Absorption Altered due to Increased Gastrointestinal Motility Clinical Impact The effect of metoclopramide on other drugs is variable. Increased gastrointestinal (GI) motility by metoclopramide may impact absorption of other drugs leading to decreased or increased drug exposure. Intervention Drugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspension Interaction does not apply to posaconazole delayed-release tablet. , fosfomycin) : Monitor for reduced therapeutic effect of the interacting drug.

For digoxin, monitor therapeutic drug concentrations and increase the digoxin dose as needed (see prescribing information for digoxin). Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine) : Monitor therapeutic drug concentrations and adjust the dose as needed. See prescribing information for the interacting drug. Insulin Clinical Impact Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose. Intervention Monitor blood glucose and adjust insulin dosage regimen as needed.

8.1 Pregnancy Risk Summary Published studies, including retrospective cohort studies, national registry studies, and meta-analyses, do not report a consistent pattern or a consistently increased risk of adverse pregnancy-related outcomes with oral use of metoclopramide during pregnancy. However, available data from a case report of GIMOTI use in pregnancy is insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are potential risks to the neonate following exposure in utero to metoclopramide during delivery (see Clinical Considerations ).

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) (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Fetal/Neonatal Adverse Reactions Metoclopramide crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery. Monitor neonates for extrapyramidal signs [see Warnings and Precautions ( 5.1 , 5.2) , Use in Specific Populations ( 8.4 )] . Data Animal Data Reproduction studies have been performed following administration of oral metoclopramide during organogenesis in pregnant rats at about 6 times the MRHD calculated on body surface area and in pregnant rabbits at about 12 times the MRHD calculated on body surface area.

No evidence of adverse developmental effects due to metoclopramide was observed.