Limitations of Use:

GIMOTI is not recommended for use in:

Missed or Incomplete Doses

Storage

Discard GIMOTI 4 weeks after opening even if the bottle contains unused drug.

Adults Less Than 65 Years of Age: The recommended dosage of GIMOTI for the treatment of acute and recurrent diabetic gastroparesis in adults is 1 spray (15 mg) in one nostril, 30 minutes before each meal and at bedtime (maximum of four times daily) for 2 to 8 weeks, depending on symptomatic response.

Adults 65 Years of Age and Older: Elderly patients may be more sensitive to the adverse effects of metoclopramide and require a lower starting dosage [see Warnings and Precautions (5.1)]. GIMOTI is not recommended in geriatric patients as initial therapy.

Geriatric patients receiving an alternative metoclopramide product at a stable dosage of 10 mg four times daily can be switched to GIMOTI 1 spray (15 mg) in one nostril, 30 minutes before each meal and at bedtime (maximum four times daily) for 2 to 8 weeks, depending on symptomatic response. Avoid treatment with metoclopramide (all dosage forms and routes of administration) for longer than 12 weeks [see Dosage and Administration (2.1)].

Nasal Spray: 15 mg of metoclopramide in each 70 microliter spray. GIMOTI is an aqueous solution supplied in an amber glass bottle fitted with a metered spray pump attachment.

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GIMOTI is contraindicated:

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Metoclopramide can cause tardive dyskinesia (TD), a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. The risk of developing TD and the likelihood that TD will become irreversible increases with duration of treatment and total cumulative dosage. Additionally, the risk of developing TD is increased among the elderly, especially elderly women [see Use in Specific Populations (8.5)], and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with metoclopramide for longer than 12 weeks. GIMOTI is not recommended in geriatric patients as initial therapy [see Dosage and Administration (2.2)].

Discontinue GIMOTI immediately in patients who develop signs and symptoms of TD. Consider treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after GIMOTI is withdrawn.

Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. GIMOTI is contraindicated in patients with a history of TD [see Contraindications (4)]. Avoid GIMOTI in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).

In addition to TD, metoclopramide may cause other extrapyramidal symptoms (EPS), parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue GIMOTI.

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. Avoid GIMOTI in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics.

Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.

In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.

Management of NMS includes:

Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid GIMOTI use in patients with a history of depression.

Metoclopramide may elevate blood pressure. In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, avoid GIMOTI use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions (7.1)].

There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. GIMOTI is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [see Contraindications (4)]. Discontinue GIMOTI in any patient with a rapid rise in blood pressure.

Because metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue GIMOTI if any of these adverse reactions occur.

As with other dopamine D2 receptor antagonists, metoclopramide elevates prolactin levels. Hyperprolactinemia may suppress hypothalamic gonadotropin-releasing hormone, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been 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 [see Nonclinical Toxicology (13.1)].

Metoclopramide may impair the mental and/or physical abilities required for the 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 GIMOTI or the interacting drug, depending on the importance of the drug to the patient [see Drug Interactions (7.1)].

Patients with moderate or severe renal or hepatic impairment, patients who are CYP2D6 poor metabolizers, and patients concurrently using strong CYP2D6 inhibitors have increased exposure to metoclopramide from GIMOTI due to reduced metabolism or excretion which may lead to an increased risk of adverse reactions, including tardive dyskinesia. Use of GIMOTI is not recommended in these patient populations since the dose of GIMOTI cannot be adjusted to reduce exposure [see Drug Interactions (7.1), Use in Specific Populations (8.6, 8.7, 8.9)].

Safety of GIMOTI

In a randomized, placebo-controlled clinical trial of 190 male and female patients of GIMOTI 14 mg, a slightly lower than recommended dosage, administered nasally four times daily for 4 weeks, dysgeusia was the most commonly reported adverse reaction (15% of GIMOTI-treated patients and 4% of placebo-treated patients). Other adverse reactions were similar to those reported for oral metoclopramide.

Safety of Oral Metoclopramide

The most common adverse reactions (in approximately 10% of patients receiving the recommended oral metoclopramide dosage of 10 mg four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of metoclopramide administration.

Adverse reactions, especially those involving the nervous system, occurred after stopping metoclopramide including dizziness, nervousness, and headaches.

Central Nervous System Disorders

Endocrine Disorders: Fluid retention secondary to transient elevation of aldosterone, galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia

Cardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention

Gastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)

Hepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential

Renal and Urinary Disorders: Urinary frequency, urinary incontinence

Hematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia

Hypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria, rash, angioedema, including glossal or laryngeal edema

Eye Disorders: Visual disturbances

Metabolism Disorders: Porphyria

Table 1 displays the effects of other drugs on metoclopramide.

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 1. Effects of Other Drugs on Metoclopramide</span> </caption> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="75%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Antipsychotics</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS).</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Avoid concomitant use <span class="Italics">[see <a href="#S5.1">Warnings and Precautions (5.1</a>, <a href="#S5.2">5.2</a>, <a href="#S5.3">5.3)</a>].</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category Above</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Increased plasma concentrations of metoclopramide; risk of exacerbation of extrapyramidal symptoms <span class="Italics">[see <a href="#S12.3">Clinical Pharmacology (12.3)</a>].</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Use of GIMOTI is not recommended <span class="Italics">[see <a href="#S5.9">Warnings and Precautions (5.9)</a>]</span>.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Examples</span></td><td align="left" class="Rrule">quinidine, bupropion, fluoxetine, and paroxetine</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Monoamine Oxidase Inhibitors</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Increased risk of hypertension <span class="Italics">[see <a href="#S5.5">Warnings and Precautions (5.5)</a>].</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Avoid concomitant use.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Central Nervous System (CNS) Depressants</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Increased risk of CNS depression <span class="Italics">[see <a href="#S5.8">Warnings and Precautions (5.8)</a>].</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Avoid GIMOTI or the interacting drug, depending on the importance of the drug to the patient.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Examples</span></td><td align="left" class="Rrule">alcohol, sedatives, hypnotics, opiates, and anxiolytics</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Drugs that Impair Gastrointestinal Motility</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Potential for decreased effect of metoclopramide due to opposing effects on gastrointestinal motility.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Monitor for reduced effect on gastrointestinal motility.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Examples</span></td><td align="left" class="Rrule">antiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiates</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Dopaminergic Agonists and Other Drugs that Increase Dopamine Concentrations</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Decreased therapeutic effect of metoclopramide due to opposing effects on dopamine.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Monitor for reduced therapeutic effect.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  <span class="Italics">Examples</span></td><td align="left" class="Rrule">apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine</td> </tr> </tbody> </table></div>

Table 2 displays the effects of metoclopramide on other drugs.

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 2. Effects of Metoclopramide on Other Drugs</span> </caption> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="75%"/> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Interaction does not apply to posaconazole delayed-release tablet.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms).</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Avoid concomitant use <span class="Italics">[see <a href="#S5.2">Warnings and Precautions (5.2)</a>]</span>.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Examples</span></td><td align="left" class="Rrule">Apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotine</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Succinylcholine, Mivacurium</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">Metoclopramide inhibits plasma cholinesterase leading to enhanced neuromuscular blockade.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule">Monitor for signs and symptoms of prolonged neuromuscular blockade</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Drugs with Absorption Altered due to Increased Gastrointestinal Motility</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Clinical Impact</span></td><td align="left" class="Rrule">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.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  <span class="Italics">Intervention</span></td><td align="left" class="Rrule"><span class="Underline">Drugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspension<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a>, fosfomycin)</span>: Monitor for reduced therapeutic effect of the interacting drug.<br/>For digoxin, monitor therapeutic drug concentrations and increase the digoxin dose as needed (see prescribing information for digoxin).<br/> <span class="Underline">Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine)</span>: Monitor therapeutic drug concentrations and adjust the dose as needed. See prescribing information for the interacting drug.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Insulin</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Italics">  Clinical Impact</span></td><td align="left" class="Rrule">Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"><span class="Italics">  Intervention</span></td><td align="left" class="Rrule">Monitor blood glucose and adjust insulin dosage regimen as needed.</td> </tr> </tbody> </table></div>

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 estimated 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.

Risk Summary

There are no data on the presence of metoclopramide in human milk following nasal administration; however, published data report the presence of metoclopramide in human milk in variable amounts following oral administration (see Data). Systemic exposure following nasal administration of GIMOTI 15 mg is expected to be similar to oral administration of metoclopramide 10 mg [see Clinical Pharmacology (12.3)]. Breastfed infants exposed to metoclopramide have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation (see Clinical Considerations). Metoclopramide elevates prolactin levels [see Warnings and Precautions (5.7)]; however, the published data are not adequate to support drug effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for GIMOTI and any potential adverse effects on the breastfed child from GIMOTI or from the underlying maternal condition.

Clinical Considerations

Monitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].

Data

In published clinical studies, the estimated amount of metoclopramide received by the breastfed infant was less than 10% of the maternal weight-adjusted oral dose. In one study, the estimated daily amount of metoclopramide received by infants from breast milk ranged from 6 to 24 mcg/kg/day in early puerperium (3 to 9 days postpartum) and from 1 to 13 mcg/kg/day at 8 to 12 weeks postpartum.

Metoclopramide is not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of GIMOTI in pediatric patients have not been established.

Dystonias and other extrapyramidal symptoms associated with metoclopramide are more common in pediatric patients than in adults [see Indications and Usage (1), Warnings and Precautions (5.1, 5.2)]. In addition, neonates have reduced levels of NADH-cytochrome b5 reductase, making them more susceptible to methemoglobinemia, a possible adverse reaction of metoclopramide use in neonates [see Use in Specific Populations (8.8)].

Metoclopramide is known to be substantially excreted by the kidney, and the risk of adverse reactions, including tardive dyskinesia (TD), may be greater in patients with impaired renal function [see Warnings and Precautions (5.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Elderly patients are more likely to have decreased renal function and may be more sensitive to the adverse effects of metoclopramide, especially elderly women, and require a lower starting dosage. GIMOTI is not recommended in geriatric patients as initial therapy. Geriatric patients receiving an alternative metoclopramide product at a stable dosage of 10 mg four times daily can be switched to GIMOTI [see Dosage and Administration (2.2)].

The clearance of metoclopramide is decreased and the systemic exposure is increased in patients with moderate to severe renal impairment compared to patients with normal renal function, which may increase the risk of adverse reactions [see Clinical Pharmacology (12.3)]. GIMOTI is not recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute), including those receiving hemodialysis and continuous ambulatory peritoneal dialysis [see Warnings and Precautions (5.9)]. Use the recommended dosage of GIMOTI in patients with mild renal impairment (creatinine clearance 60 mL/minute or greater) [see Dosage and Administration (2.2)].

Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic metoclopramide clearance (by approximately 50%) compared to patients with normal hepatic function [see Clinical Pharmacology (12.3)]. The resulting increase in metoclopramide blood concentrations increases the risk of adverse reactions. There are no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). GIMOTI is not recommended in patients with moderate or severe (Child-Pugh B or C) hepatic impairment [see Warnings and Precautions (5.9)]. Use the recommended dosage of GIMOTI in patients with mild hepatic impairment (Child-Pugh A) [see Dosage and Administration (2.2)].

Metoclopramide, by producing a transient increase in plasma aldosterone, may increase the risk of fluid retention in patients with hepatic impairment [see Warnings and Precautions (5.6)]. Monitor patients with hepatic impairment for the occurrence of fluid retention and volume overload.

Metoclopramide-treated patients with NADH-cytochrome b5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia. For patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended. Methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal [see Overdosage (10)].

Metoclopramide is a substrate of CYP2D6. The elimination of metoclopramide may be slowed in patients who are CYP2D6 poor metabolizers (compared to patients who are CYP2D6 intermediate, extensive, or ultra-rapid metabolizers), possibly increasing the risk of dystonic and other adverse reactions to metoclopramide [see Clinical Pharmacology (12.3)]. GIMOTI is not recommended in patients who are CYP2D6 poor metabolizers [see Warnings and Precautions (5.9)].

Manifestations of metoclopramide overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with metoclopramide use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with metoclopramide overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)].

{ "type": "p", "children": [], "text": "Manifestations of metoclopramide overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with metoclopramide use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with metoclopramide overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)].\n" }

There are no specific antidotes for metoclopramide overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

{ "type": "p", "children": [], "text": "There are no specific antidotes for metoclopramide overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.\n" }

Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal.

{ "type": "p", "children": [], "text": "Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal." }

Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide.

{ "type": "p", "children": [], "text": "Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide." }

Metoclopramide hydrochloride, the active ingredient in GIMOTI, is a dopamine-2 receptor antagonist. Metoclopramide hydrochloride is a white, crystalline, odorless substance, freely soluble in water. Its chemical name is 4-amino­5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate.

{ "type": "p", "children": [], "text": "Metoclopramide hydrochloride, the active ingredient in GIMOTI, is a dopamine-2 receptor antagonist. Metoclopramide hydrochloride is a white, crystalline, odorless substance, freely soluble in water. Its chemical name is 4-amino­5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate." }

The molecular formula is C14H22ClN3O2∙HCl∙H2O. Its molecular weight is 354.3. The structural formula is:

{ "type": "p", "children": [], "text": "The molecular formula is C14H22ClN3O2∙HCl∙H2O. Its molecular weight is 354.3. The structural formula is:" }

GIMOTI (metoclopramide) nasal spray is for nasal administration. The product is supplied as an aqueous solution with a pH of 5.5 ± 0.5 in a 10 mL amber glass vial fitted with a metered spray pump attachment. Each unit contains 9.8 mL.

{ "type": "p", "children": [], "text": "GIMOTI (metoclopramide) nasal spray is for nasal administration. The product is supplied as an aqueous solution with a pH of 5.5 ± 0.5 in a 10 mL amber glass vial fitted with a metered spray pump attachment. Each unit contains 9.8 mL." }

Each 70 microliter spray contains 15 mg metoclopramide, equivalent to 17.73 mg of metoclopramide hydrochloride. Inactive ingredients consist of benzalkonium chloride, citric acid monohydrate, edetate disodium dihydrate, purified water, sodium citrate dihydrate, and sorbitol.

{ "type": "p", "children": [], "text": "Each 70 microliter spray contains 15 mg metoclopramide, equivalent to 17.73 mg of metoclopramide hydrochloride. Inactive ingredients consist of benzalkonium chloride, citric acid monohydrate, edetate disodium dihydrate, purified water, sodium citrate dihydrate, and sorbitol." }

Metoclopramide stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of metoclopramide in the treatment of gastroesophageal reflux and acute and recurrent diabetic gastroparesis has not been fully established. It seems to sensitize tissues to the action of acetylcholine. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.

Metoclopramide increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.

Cardiac Electrophysiology

In a randomized, double-blind, positive-controlled thorough ECG study in 48 healthy subjects, a single administration of 80 mg metoclopramide nasal spray (approximately 5 times the recommended GIMOTI dose) had no effect on the QTc interval.

Absorption

The absolute bioavailability of metoclopramide following nasal administration of 10 mg metoclopramide is 47% in healthy subjects compared to intravenous injection of metoclopramide 10 mg. The systemic absorption after nasal administration is lower than that after oral administration given the same dose. Following nasal administration of GIMOTI 15 mg in healthy subjects, the systemic exposure (Cmax and AUC) to metoclopramide and the time to reach Cmax (Tmax) were similar to orally administered 10 mg metoclopramide tablet.

After single nasal administration of metoclopramide at doses ranging from 10 mg to 80 mg in healthy subjects, there was a dose-proportional increase in the mean values for Cmax and AUC.

The pharmacokinetic parameters of metoclopramide in healthy subjects following a single nasal administration of GIMOTI 15 mg are summarized in Table 3.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 3. Summary of Metoclopramide Pharmacokinetic Parameters in Healthy Subjects after a Single Nasal Administration of GIMOTI 15 mg </span> </caption> <col align="left" valign="middle" width="45%"/> <col align="center" valign="middle" width="55%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Parameter <a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></th><th align="center" class="Rrule">GIMOTI<br/>15 mg</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Arithmetic mean (SD) except t<span class="Sub">max</span> for which the median (range) is reported.</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">†</a> </dt> <dd>N = 93</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">N</td><td align="center" class="Rrule">94</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">C<span class="Sub">max</span> (ng/mL)</td><td align="center" class="Rrule">41.0 (19.9)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">t<span class="Sub">max</span> (h)</td><td align="center" class="Rrule">1.25<br/>(0.50 – 3.50)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">AUC<span class="Sub">0-t</span> (ng∙h/mL)</td><td align="center" class="Rrule">349 (174.7)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">AUC<span class="Sub">0-inf </span>(ng∙h/mL) <a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a></td><td align="center" class="Rrule">367 (184.8)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">t<span class="Sub">1/2 </span>(h)</td><td align="center" class="Rrule">8.1 (2.0)</td> </tr> </tbody> </table></div>

Distribution

Metoclopramide is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg), which suggests extensive distribution of drug to the tissues.

Elimination

The mean elimination half-life in individuals with normal renal function is approximately 8 hours for administration with GIMOTI 15 mg.

Metabolism: Metoclopramide undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Warnings and Precautions (5.9), Use in Specific Populations (8.9)].

Excretion: Approximately 85% of the radioactivity of an orally administered dose appeared in the urine within 72 hours. After oral administration of 10 or 20 mg, a mean of 18% and 22% of the dose, respectively, was recovered as free metoclopramide in urine within 36 hours.

Specific Populations

Patients with Renal Impairment: In a study of 24 patients with varying degrees of renal impairment (moderate, severe, and end-stage renal disease [ESRD] requiring dialysis), the systemic exposure (AUC) of metoclopramide following oral administration in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of metoclopramide in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Warnings and Precautions (5.9), Use in Specific Populations (8.6)].

Patients with Hepatic Impairment: In a group of 8 patients with severe hepatic impairment (Child-Pugh C), the average metoclopramide clearance was reduced by approximately 50% compared to patients with normal hepatic function after administration of oral metoclopramide [see Warnings and Precautions (5.9), Use in Specific Populations (8.7)].

Sex and Body Weight: The AUC0-t and Cmax of metoclopramide were 34% and 42% higher in females than in males, respectively, following administration of metoclopramide nasal spray to healthy subjects. Based on population pharmacokinetic analysis, lean body weight (34.3 to 93.5 kg) has a significant impact on metoclopramide pharmacokinetics, with lower systemic exposure expected with higher lean body weight. The clinical significance of these findings is unknown.

Drug Interactions

Effect of Metoclopramide on CYP2D6 Substrates

Although in vitro studies suggest that metoclopramide can inhibit CYP2D6, metoclopramide is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.

Effect of CYP2D6 Inhibitors on Metoclopramide

Metoclopramide 20 mg was orally administered as a single dose to 24 healthy males, without (Period 1) and with (Period 2) a concomitant dose of fluoxetine 60 mg (a strong CYP2D6 inhibitor). Between the two periods, fluoxetine was administered orally for 8 days. The subjects who received concomitant metoclopramide and fluoxetine had a 40% and 90% increase in metoclopramide Cmax and AUC0-inf, respectively, compared to subjects who received metoclopramide alone. The mean half-life for metoclopramide was increased from 5.5 (±1.1) hours to 8.5 (±2.2) hours with concomitant fluoxetine [see Warnings and Precautions (5.9), Drug Interactions (7.1)].

Carcinogenesis

A 77-week study was conducted in rats with oral metoclopramide doses up to 40 mg/kg/day (about 6 times the maximum recommended human dose on body surface area basis). Metoclopramide elevated prolactin levels, and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of metoclopramide [see Warnings and Precautions (5.7)]. In a rat model for assessing the tumor promotion potential, a 2-week oral treatment with metoclopramide at a dose of 260 mg/kg/day (about 35 times the MRHD based on body surface area) enhanced the tumorigenic effect of N-nitrosodiethylamine.

Mutagenesis

Metoclopramide was positive in the in vitro Chinese hamster lung cell/HGPRT forward mutation assay for mutagenic effects and in the in vitro human lymphocyte chromosome aberration assay for clastogenic effects. It was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis assay with rat and human hepatocytes, and the in vivo rat micronucleus assay.

Impairment of Fertility

Metoclopramide at intramuscular doses up to 20 mg/kg/day (about 3 times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

The effectiveness of GIMOTI has been established based on studies of oral metoclopramide for the relief of symptoms in adults with acute and recurrent diabetic gastroparesis.

{ "type": "p", "children": [], "text": "The effectiveness of GIMOTI has been established based on studies of oral metoclopramide for the relief of symptoms in adults with acute and recurrent diabetic gastroparesis. " }

Store at 20°C to 25°C (68°F to 77°F) excursions permitted 15°C to 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Discard GIMOTI 4 weeks after opening even if the bottle contains unused medicine.

Adverse Reactions

Inform the patients or their caregivers that metoclopramide can cause serious adverse reactions. Instruct patients to discontinue GIMOTI and contact a healthcare provider immediately if the following serious reactions occur:

Inform the patient or their caregiver that metoclopramide can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle [see Warnings and Precautions (5.8)].

Drug Interactions

Inform the patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression [see Drug Interactions (7.1, 7.2)]. Explain that the prescriber of any other medication must be made aware that the patient is taking GIMOTI.

Administration Instructions [see Dosage and Administration (2.1)]

Advise the patients or their caregiver to read the Instructions for Use on how to appropriately administer GIMOTI:

Missed or Incomplete Doses

Manufactured for: Evoke Pharma, Inc. Solana Beach, CA 92075 USA By: Patheon, a Division of Thermo Fisher Bourgoin Jallieu Cedex, 38307, France

{ "type": "p", "children": [], "text": "Manufactured for: Evoke Pharma, Inc. Solana Beach, CA 92075 USA By: Patheon, a Division of Thermo Fisher Bourgoin Jallieu Cedex, 38307, France " }

© 2021 Evoke Pharma, Inc. All rights reserved.

{ "type": "p", "children": [], "text": "© 2021 Evoke Pharma, Inc. All rights reserved. " }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="80%"/> <col align="right" valign="top" width="20%"/> <tfoot> <tr class="First Last"> <td align="left">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align="right">Approved: June 2020</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="2"><span class="Bold">Medication Guide</span> <br/>GIMOTI™ (jye-MOH-tee)<br/>(metoclopramide) <br/>nasal spray</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2">Read this Medication Guide before you start taking GIMOTI and each time you get a refill. There may be new information. If you take another product that contains metoclopramide (such as REGLAN tablets, REGLAN injection, metoclopramide orally disintegrating tablets [ODT], or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold"><a name="Whatis"></a>What is the most important information I should know about GIMOTI?</span> <br/> <span class="Bold">GIMOTI can cause serious side effects, including:</span> <br/> <span class="Bold">Tardive dyskinesia (abnormal muscle movements).</span> These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping GIMOTI. <br/>Your chances for getting tardive dyskinesia increase:<ul> <li>the longer you take GIMOTI and the more GIMOTI you take. You should not take GIMOTI for more than 8 weeks at a time, and you should not take products containing metoclopramide (including GIMOTI) for more than 12 weeks at a time.</li> <li>if you are older, especially if you are an older woman.</li> <li>because you have diabetes.</li> </ul>It is not possible for your healthcare provider to know if <span class="Bold">you</span> will get tardive dyskinesia if you take GIMOTI.<br/>Call your healthcare provider right away if you get movements you cannot stop or control, such as:<ul> <li>lip smacking, chewing, or puckering up your mouth</li> <li>frowning or scowling</li> <li>sticking out your tongue</li> <li>blinking and moving your eyes</li> <li>shaking of your arms and legs</li> </ul>Your healthcare provider may stop treatment with GIMOTI if you develop signs or symptoms of tardive dyskinesia.<br/> See the section <span class="Bold">"<a href="#Whatare">What are the possible side effects of GIMOTI?</a>"</span> for more information about side effects.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What is GIMOTI?</span> <ul> <li>GIMOTI is a prescription medicine used in adults to relieve the symptoms of slow stomach emptying in people with diabetes.</li> <li>GIMOTI is <span class="Bold">not recommended</span> for use in people who:<ul class="Circle"> <li>have kidney or liver problems.</li> <li>have been told that an enzyme in their body, called CYP2D6, breaks down (metabolizes) certain medicines in the body too slowly.</li> <li>are also taking medicine called CYP2D6 inhibitors, which slows how fast the body breaks down (metabolizes) certain medicines. </li> </ul> </li> <li>GIMOTI is not recommended for use in children.</li> <li>It is not known if GIMOTI is safe and effective in children. </li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Do not take GIMOTI if you:</span> <ul> <li>have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking GIMOTI or a medicine that works like GIMOTI.</li> <li>have stomach or intestine problems that could get worse with GIMOTI, such as bleeding, blockage, or a tear in the stomach or bowel wall.</li> <li>have a type of tumor that can cause high blood pressure, such as pheochromocytoma.</li> <li>have epilepsy (seizures). GIMOTI can increase your chance for seizures and make them worse.</li> <li>are allergic to metoclopramide. GIMOTI can cause serious allergic reactions. Stop taking GIMOTI right away and get emergency help if you have any of these symptoms:<ul class="Circle"> <li>swelling of your tongue, throat, lips, eyes, or face</li> <li>trouble swallowing or breathing</li> <li>skin rash, hives, sores in your mouth, or skin blisters</li> </ul> </li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Before taking GIMOTI, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul> <li>take insulin for your diabetes. Your dose may need to be changed.</li> <li>had problems controlling your muscle movements after taking any medicine.</li> <li>have Parkinson's disease.</li> <li>have kidney or liver disease.</li> <li>have or had depression or mental illness.</li> <li>have high blood pressure.</li> <li>have heart failure or heart rhythm problems.</li> <li>have breast cancer.</li> <li>drink alcohol.</li> <li>are pregnant or plan to become pregnant. GIMOTI may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking GIMOTI.</li> <li>are breastfeeding or plan to breastfeed. GIMOTI can pass into your breast milk and may harm your baby. It is important that you tell your baby's healthcare provider you are taking GIMOTI. You and your healthcare provider should decide if you will take GIMOTI or breastfeed.</li> </ul>Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>GIMOTI may affect the way other medicines work and other medicines may affect how GIMOTI works. <br/>Tell your healthcare provider before you start or stop other medicines.<br/> <span class="Bold">Especially tell your healthcare provider if you take:</span> <ul> <li>another medicine that contains metoclopramide, such as REGLAN tablets, REGLAN injection, metoclopramide orally disintegrating tablets (ODT), or metoclopramide oral solution.</li> <li>a medicine for Parkinson's disease.</li> <li>a blood pressure medicine.</li> <li>a medicine for depression, especially a monoamine oxidase inhibitor (MAOI).</li> <li>an anti-psychotic medicine, used to treat mental illness such as schizophrenia.</li> <li>insulin.</li> <li>medicines that can make you sleepy, such as anxiety medicines, sleep medicines, and narcotics.</li> </ul>If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.<br/> <span class="Bold">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">How should I take GIMOTI?</span> <ul> <li> <span class="Bold">Read the step-by-step Instructions for Use that come with your GIMOTI prescription.</span> </li> <li>Take GIMOTI exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.</li> <li>GIMOTI comes as a liquid in a glass bottle with a spray pump attached.</li> <li>You should not take GIMOTI for more than 8 weeks at a time.</li> <li>You should not take medicines containing metoclopramide (including GIMOTI) for more than 12 weeks at a time.</li> <li>Take GIMOTI at least 30 minutes before each meal and at bedtime.</li> <li>If you are not certain that the spray entered the nose, skip the dose and take your next dose at your regular schedule time. Do not take an extra dose at the schedule time. If you miss a dose of GIMOTI, skip that dose and take your next dose at your regular scheduled time. Do not take an extra dose to make up for a missed dose.</li> <li>If you take too much GIMOTI, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What should I avoid while taking GIMOTI?</span> <ul> <li>Do not drink alcohol while taking GIMOTI. Alcohol may make some side effects of GIMOTI worse, such as feeling sleepy.</li> <li>Do not drive, operate machinery, or do other dangerous activities until you know how GIMOTI affects you. GIMOTI may cause sleepiness or dizziness.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold"><a name="Whatare"></a>What are the possible side effects of GIMOTI? GIMOTI can cause serious side effects, including:</span> <ul> <li> <span class="Bold">Tardive dyskinesia (abnormal muscle movements).</span> See <span class="Bold">"<a href="#Whatis">What is the most important information I need to know about GIMOTI?</a>"</span> </li> <li> <span class="Bold">Other changes in muscle control and movement, such as:</span> <ul class="Circle"> <li> <span class="Bold">Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia).</span> These muscle spasms can cause abnormal movements and body positions and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age.</li> <li> <span class="Bold">Parkinsonism.</span> Symptoms include slight shaking, body stiffness, and trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking GIMOTI.</li> <li> <span class="Bold">Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia).</span> Symptoms can include feeling jittery, anxious, irritated, or unable to sleep (insomnia), feeling the need to walk around (pacing), and tapping your feet. Your healthcare provider may stop your treatment with GIMOTI if you develop these symptoms.</li> </ul> </li> <li> <span class="Bold">Neuroleptic Malignant Syndrome (NMS).</span> NMS is a very rare, but very serious condition that can happen with GIMOTI. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.</li> <li> <span class="Bold">Depression, thoughts about suicide, and suicide.</span> Some people who take GIMOTI may become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken metoclopramide have ended their own lives (suicide).</li> <li> <span class="Bold">High blood pressure.</span> GIMOTI can cause your blood pressure to increase. Your healthcare provider may stop your treatment if GIMOTI causes your blood pressure to increase very fast. </li> <li> <span class="Bold">Too much body water.</span> People who have certain liver problems or heart failure and take GIMOTI may hold too much water in their body (fluid retention). Tell your healthcare provider right away if you have sudden weight gain, or swelling of your hands, legs, or feet.</li> <li> <span class="Bold">Increased prolactin.</span> Tell your healthcare provider if your menstrual periods stop or your breasts get larger and make milk. These symptoms go away when you stop taking GIMOTI.</li> </ul> <span class="Bold">Call your healthcare provider and get medical help right away if you:</span> <ul> <li>feel depressed or have thoughts about hurting or killing yourself</li> <li>have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating</li> <li>have muscle movements you cannot stop or control</li> <li>have muscle movements that are new or unusual</li> </ul>The most common side effects of GIMOTI include:<ul> <li>unpleasant taste </li> <li>headache</li> <li>tiredness</li> </ul>You may have more side effects the longer you take GIMOTI and the more GIMOTI you take.<br/>You may still have side effects after stopping GIMOTI. You may have symptoms from stopping GIMOTI such as headaches and feeling dizzy or nervous.<br/>Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of GIMOTI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">How should I store GIMOTI?</span> <ul> <li>Store GIMOTI at room temperature between 68°F to 77°F (20°C to 25°C). </li> <li>Throw away (discard) GIMOTI 4 weeks after opening even if the bottle contains unused medicine. </li> </ul> <span class="Bold">Keep GIMOTI and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">General information about the safe and effective use of GIMOTI.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use GIMOTI for a condition for which it was not prescribed. Do not give GIMOTI to other people, even if they have the same symptoms that you have. It may harm them.<br/>You can ask your pharmacist or healthcare provider for information about GIMOTI that is written for health professionals.</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What are the ingredients in GIMOTI? </span> <br/> <span class="Bold">Active ingredient:</span> metoclopramide <br/> <span class="Bold">Inactive ingredients:</span> benzalkonium chloride, citric acid monohydrate, edetate disodium dihydrate, purified water, sodium citrate dihydrate, sorbitol.<br/>Manufactured for Evoke Pharma, Inc. by Patheon, a Division of Thermo Fisher.<br/>GIMOTI is a trademark of Evoke Pharma. <span class="Sup">©</span>2020 Evoke Pharma, Inc. All rights reserved.<br/>For more information, go to www.evokepharma.com or call 1-833-4-GIMOTI (1-833-444-6684).</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"80%\"/>\n<col align=\"right\" valign=\"top\" width=\"20%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align=\"right\">Approved: June 2020</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Medication Guide</span>\n<br/>GIMOTI™ (jye-MOH-tee)<br/>(metoclopramide) <br/>nasal spray</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\">Read this Medication Guide before you start taking GIMOTI and each time you get a refill. There may be new information. If you take another product that contains metoclopramide (such as REGLAN tablets, REGLAN injection, metoclopramide orally disintegrating tablets [ODT], or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\"><a name=\"Whatis\"></a>What is the most important information I should know about GIMOTI?</span>\n<br/>\n<span class=\"Bold\">GIMOTI can cause serious side effects, including:</span>\n<br/>\n<span class=\"Bold\">Tardive dyskinesia (abnormal muscle movements).</span> These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping GIMOTI. <br/>Your chances for getting tardive dyskinesia increase:<ul>\n<li>the longer you take GIMOTI and the more GIMOTI you take. You should not take GIMOTI for more than 8 weeks at a time, and you should not take products containing metoclopramide (including GIMOTI) for more than 12 weeks at a time.</li>\n<li>if you are older, especially if you are an older woman.</li>\n<li>because you have diabetes.</li>\n</ul>It is not possible for your healthcare provider to know if <span class=\"Bold\">you</span> will get tardive dyskinesia if you take GIMOTI.<br/>Call your healthcare provider right away if you get movements you cannot stop or control, such as:<ul>\n<li>lip smacking, chewing, or puckering up your mouth</li>\n<li>frowning or scowling</li>\n<li>sticking out your tongue</li>\n<li>blinking and moving your eyes</li>\n<li>shaking of your arms and legs</li>\n</ul>Your healthcare provider may stop treatment with GIMOTI if you develop signs or symptoms of tardive dyskinesia.<br/> See the section <span class=\"Bold\">\"<a href=\"#Whatare\">What are the possible side effects of GIMOTI?</a>\"</span> for more information about side effects.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What is GIMOTI?</span>\n<ul>\n<li>GIMOTI is a prescription medicine used in adults to relieve the symptoms of slow stomach emptying in people with diabetes.</li>\n<li>GIMOTI is <span class=\"Bold\">not recommended</span> for use in people who:<ul class=\"Circle\">\n<li>have kidney or liver problems.</li>\n<li>have been told that an enzyme in their body, called CYP2D6, breaks down (metabolizes) certain medicines in the body too slowly.</li>\n<li>are also taking medicine called CYP2D6 inhibitors, which slows how fast the body breaks down (metabolizes) certain medicines. </li>\n</ul>\n</li>\n<li>GIMOTI is not recommended for use in children.</li>\n<li>It is not known if GIMOTI is safe and effective in children. </li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Do not take GIMOTI if you:</span>\n<ul>\n<li>have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking GIMOTI or a medicine that works like GIMOTI.</li>\n<li>have stomach or intestine problems that could get worse with GIMOTI, such as bleeding, blockage, or a tear in the stomach or bowel wall.</li>\n<li>have a type of tumor that can cause high blood pressure, such as pheochromocytoma.</li>\n<li>have epilepsy (seizures). GIMOTI can increase your chance for seizures and make them worse.</li>\n<li>are allergic to metoclopramide. GIMOTI can cause serious allergic reactions. Stop taking GIMOTI right away and get emergency help if you have any of these symptoms:<ul class=\"Circle\">\n<li>swelling of your tongue, throat, lips, eyes, or face</li>\n<li>trouble swallowing or breathing</li>\n<li>skin rash, hives, sores in your mouth, or skin blisters</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Before taking GIMOTI, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul>\n<li>take insulin for your diabetes. Your dose may need to be changed.</li>\n<li>had problems controlling your muscle movements after taking any medicine.</li>\n<li>have Parkinson's disease.</li>\n<li>have kidney or liver disease.</li>\n<li>have or had depression or mental illness.</li>\n<li>have high blood pressure.</li>\n<li>have heart failure or heart rhythm problems.</li>\n<li>have breast cancer.</li>\n<li>drink alcohol.</li>\n<li>are pregnant or plan to become pregnant. GIMOTI may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking GIMOTI.</li>\n<li>are breastfeeding or plan to breastfeed. GIMOTI can pass into your breast milk and may harm your baby. It is important that you tell your baby's healthcare provider you are taking GIMOTI. You and your healthcare provider should decide if you will take GIMOTI or breastfeed.</li>\n</ul>Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>GIMOTI may affect the way other medicines work and other medicines may affect how GIMOTI works. <br/>Tell your healthcare provider before you start or stop other medicines.<br/>\n<span class=\"Bold\">Especially tell your healthcare provider if you take:</span>\n<ul>\n<li>another medicine that contains metoclopramide, such as REGLAN tablets, REGLAN injection, metoclopramide orally disintegrating tablets (ODT), or metoclopramide oral solution.</li>\n<li>a medicine for Parkinson's disease.</li>\n<li>a blood pressure medicine.</li>\n<li>a medicine for depression, especially a monoamine oxidase inhibitor (MAOI).</li>\n<li>an anti-psychotic medicine, used to treat mental illness such as schizophrenia.</li>\n<li>insulin.</li>\n<li>medicines that can make you sleepy, such as anxiety medicines, sleep medicines, and narcotics.</li>\n</ul>If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.<br/>\n<span class=\"Bold\">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">How should I take GIMOTI?</span>\n<ul>\n<li>\n<span class=\"Bold\">Read the step-by-step Instructions for Use that come with your GIMOTI prescription.</span>\n</li>\n<li>Take GIMOTI exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.</li>\n<li>GIMOTI comes as a liquid in a glass bottle with a spray pump attached.</li>\n<li>You should not take GIMOTI for more than 8 weeks at a time.</li>\n<li>You should not take medicines containing metoclopramide (including GIMOTI) for more than 12 weeks at a time.</li>\n<li>Take GIMOTI at least 30 minutes before each meal and at bedtime.</li>\n<li>If you are not certain that the spray entered the nose, skip the dose and take your next dose at your regular schedule time. Do not take an extra dose at the schedule time. If you miss a dose of GIMOTI, skip that dose and take your next dose at your regular scheduled time. Do not take an extra dose to make up for a missed dose.</li>\n<li>If you take too much GIMOTI, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What should I avoid while taking GIMOTI?</span>\n<ul>\n<li>Do not drink alcohol while taking GIMOTI. Alcohol may make some side effects of GIMOTI worse, such as feeling sleepy.</li>\n<li>Do not drive, operate machinery, or do other dangerous activities until you know how GIMOTI affects you. GIMOTI may cause sleepiness or dizziness.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\"><a name=\"Whatare\"></a>What are the possible side effects of GIMOTI? GIMOTI can cause serious side effects, including:</span>\n<ul>\n<li>\n<span class=\"Bold\">Tardive dyskinesia (abnormal muscle movements).</span> See <span class=\"Bold\">\"<a href=\"#Whatis\">What is the most important information I need to know about GIMOTI?</a>\"</span>\n</li>\n<li>\n<span class=\"Bold\">Other changes in muscle control and movement, such as:</span>\n<ul class=\"Circle\">\n<li>\n<span class=\"Bold\">Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia).</span> These muscle spasms can cause abnormal movements and body positions and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age.</li>\n<li>\n<span class=\"Bold\">Parkinsonism.</span> Symptoms include slight shaking, body stiffness, and trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking GIMOTI.</li>\n<li>\n<span class=\"Bold\">Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia).</span> Symptoms can include feeling jittery, anxious, irritated, or unable to sleep (insomnia), feeling the need to walk around (pacing), and tapping your feet. Your healthcare provider may stop your treatment with GIMOTI if you develop these symptoms.</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Neuroleptic Malignant Syndrome (NMS).</span> NMS is a very rare, but very serious condition that can happen with GIMOTI. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.</li>\n<li>\n<span class=\"Bold\">Depression, thoughts about suicide, and suicide.</span> Some people who take GIMOTI may become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken metoclopramide have ended their own lives (suicide).</li>\n<li>\n<span class=\"Bold\">High blood pressure.</span> GIMOTI can cause your blood pressure to increase. Your healthcare provider may stop your treatment if GIMOTI causes your blood pressure to increase very fast. </li>\n<li>\n<span class=\"Bold\">Too much body water.</span> People who have certain liver problems or heart failure and take GIMOTI may hold too much water in their body (fluid retention). Tell your healthcare provider right away if you have sudden weight gain, or swelling of your hands, legs, or feet.</li>\n<li>\n<span class=\"Bold\">Increased prolactin.</span> Tell your healthcare provider if your menstrual periods stop or your breasts get larger and make milk. These symptoms go away when you stop taking GIMOTI.</li>\n</ul>\n<span class=\"Bold\">Call your healthcare provider and get medical help right away if you:</span>\n<ul>\n<li>feel depressed or have thoughts about hurting or killing yourself</li>\n<li>have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating</li>\n<li>have muscle movements you cannot stop or control</li>\n<li>have muscle movements that are new or unusual</li>\n</ul>The most common side effects of GIMOTI include:<ul>\n<li>unpleasant taste </li>\n<li>headache</li>\n<li>tiredness</li>\n</ul>You may have more side effects the longer you take GIMOTI and the more GIMOTI you take.<br/>You may still have side effects after stopping GIMOTI. You may have symptoms from stopping GIMOTI such as headaches and feeling dizzy or nervous.<br/>Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of GIMOTI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">How should I store GIMOTI?</span>\n<ul>\n<li>Store GIMOTI at room temperature between 68°F to 77°F (20°C to 25°C). </li>\n<li>Throw away (discard) GIMOTI 4 weeks after opening even if the bottle contains unused medicine. </li>\n</ul>\n<span class=\"Bold\">Keep GIMOTI and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">General information about the safe and effective use of GIMOTI.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use GIMOTI for a condition for which it was not prescribed. Do not give GIMOTI to other people, even if they have the same symptoms that you have. It may harm them.<br/>You can ask your pharmacist or healthcare provider for information about GIMOTI that is written for health professionals.</td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What are the ingredients in GIMOTI? </span>\n<br/>\n<span class=\"Bold\">Active ingredient:</span> metoclopramide <br/>\n<span class=\"Bold\">Inactive ingredients:</span> benzalkonium chloride, citric acid monohydrate, edetate disodium dihydrate, purified water, sodium citrate dihydrate, sorbitol.<br/>Manufactured for Evoke Pharma, Inc. by Patheon, a Division of Thermo Fisher.<br/>GIMOTI is a trademark of Evoke Pharma. <span class=\"Sup\">©</span>2020 Evoke Pharma, Inc. All rights reserved.<br/>For more information, go to www.evokepharma.com or call 1-833-4-GIMOTI (1-833-444-6684).</td>\n</tr>\n</tbody>\n</table></div>" }

GIMOTI™ (jye-MOH-tee) (phonetic spelling)(metoclopramide)nasal spray

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Read this Instructions for Use before you start using GIMOTI nasal spray and each time you get a refill. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

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Important information:

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Parts of your GIMOTI bottle

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Steps to use GIMOTI

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The GIMOTI nasal spray bottle is now ready for use.

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Cleaning the spray pump nozzle

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If the spray pump nozzle becomes clogged, remove it for cleaning by grasping the base of the spray nozzle and pulling up.

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Soak the spray nozzle in warm water and rinse. Do not try to unblock the spray nozzle by inserting a pin or other sharp object because this will damage the spray nozzle.

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Dry the spray nozzle at room temperature. When the spray nozzle is dry, place the dry spray nozzle back on the GIMOTI bottle.

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Disposal instructions

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The used GIMOTI nasal spray may be thrown away (discarded) in the household trash.

{ "type": "p", "children": [], "text": "The used GIMOTI nasal spray may be thrown away (discarded) in the household trash." }

Manufactured for Evoke Pharma, Inc. by Patheon, a Division of Thermo Fisher.

{ "type": "p", "children": [], "text": "Manufactured for Evoke Pharma, Inc. by Patheon, a Division of Thermo Fisher." }

GIMOTI is a trademark of Evoke Pharma. ©2020 Evoke Pharma, Inc. All rights reserved.

{ "type": "p", "children": [], "text": "GIMOTI is a trademark of Evoke Pharma. ©2020 Evoke Pharma, Inc. All rights reserved." }

For more information, go to www.evokepharma.com or call 1-833-4-GIMOTI (1-833-444-6684).

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These Instructions for Use have been approved by the U.S. Food and Drug AdministrationApproved: June 2020

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NDC 72089-307-15

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Gimoti™(metoclopramide)nasal spray

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15 mgper spray

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FOR NASAL USE ONLY

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Rx Only

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Net Content 9.8 mL112 metered sprays

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EVOKEPHARMA

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Limitations of Use:

Metoclopramide is not recommended for use in pediatric patients due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates [see Use in Specific Populations (8.4)].

Avoid treatment with metoclopramide for longer than 12 weeks because of the increased risk of developing TD with longer-term use [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

Metoclopramide may be administered continuously or intermittently in patients with symptomatic gastroesophageal reflux who fail to respond to conventional therapy:

Continuous Dosing

The recommended adult dosage of metoclopramide is 10 to 15 mg four times daily for 4 to 12 weeks. The treatment duration is determined by endoscopic response. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 60 mg.

Table 1 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

Intermittent Dosing

If symptoms only occur intermittently or at specific times of the day, administer metoclopramide in single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1.

<div class="scrollingtable"><table> <caption> <span>Table 1. Recommended Metoclopramide Dosage in Patients with Gastroesophageal Reflux</span> </caption> <col/> <col/> <col/> <thead> <tr class="First Last"> <th class="Lrule Rrule"></th><th align="center" class="Rrule"> Recommended Dosage</th><th align="center" class="Rrule"> Maximum Recommended Daily Dosage</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Elderly patients may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider a lower starting dosage of 5 mg four times daily with titration to the recommended adult dosage of 10 to 15 mg four times daily based upon response and tolerability.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule Rrule">Adult patients</td><td class="Rrule" rowspan="2">10 to 15 mg four times daily (thirty minutes before each meal and at bedtime)</td><td align="center" class="Rrule" rowspan="3">60 mg</td> </tr> <tr> <td class="Lrule Rrule">Mild hepatic impairment (Child-Pugh A)</td> </tr> <tr> <td class="Lrule Rrule">Elderly patients <span class="Italics">[see <a href="#LINK_e0253b1c-1443-4e0b-93ce-b65b57950648">Use in Specific Populations (8.5)</a>] </span></td><td class="Rrule">5 mg <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> four times daily (thirty minutes before each meal and at bedtime) </td> </tr> <tr> <td class="Lrule Rrule">Moderate or severe hepatic impairment (Child-Pugh B or C) <span class="Italics">[see <a href="#LINK_45f3365d-8301-4623-9dad-456f5b35e945">Use in Specific Populations (8.7)</a>] </span></td><td class="Rrule" rowspan="4">5 mg four times daily (thirty minutes before each meal and at bedtime), or 10 mg taken three times daily</td><td align="center" class="Rrule" rowspan="4">30 mg</td> </tr> <tr> <td class="Lrule Rrule">CYP2D6 poor metabolizers <span class="Italics">[see <a href="#LINK_ae77abd8-f24e-433a-acd8-4e1b7a7a51fe">Use in Specific Populations (8.9)</a>] </span></td> </tr> <tr> <td class="Lrule Rrule">Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) <span class="Italics">[see <a href="#LINK_7aa57b27-c393-4626-8be0-90d90166bc16">Drug Interactions (7.1)</a>] </span></td> </tr> <tr> <td class="Lrule Rrule">Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) <span class="Italics">[see <a href="#LINK_187febd7-0621-4747-ad18-ac564f14d966">Use in Specific Populations (8.6)</a>] </span></td> </tr> <tr class="Last"> <td class="Lrule Rrule">Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis <span class="Italics">[see <a href="#LINK_187febd7-0621-4747-ad18-ac564f14d966">Use in Specific Populations (8.6)</a>] </span></td><td class="Rrule">5 mg four times daily (thirty minutes before each meal and at bedtime) or 10 mg twice daily</td><td align="center" class="Rrule">20 mg</td> </tr> </tbody> </table></div>

The recommended adult dosage for the treatment of acute and recurrent diabetic gastroparesis is 10 mg four times daily for 2 to 8 weeks, depending on symptomatic response. Avoid metoclopramide treatment for greater than 12 weeks [see Warnings and Precautions (5.1)]. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 40 mg.

Table 2 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.Table 2 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

If patients with diabetic gastroparesis have severe nausea or vomiting and are unable to take metoclopramide, consider starting therapy with metoclopramide injection given intramuscularly or intravenously for up to 10 days (see the prescribing information for metoclopramide injection).If patients with diabetic gastroparesis have severe nausea or vomiting and are unable to take metoclopramide, consider starting therapy with metoclopramide injection given intramuscularly or intravenously for up to 10 days (see the prescribing information for metoclopramide injection).

<div class="scrollingtable"><table> <caption> <span>Table 2. Recommended Metoclopramide Dosage in Patients with Acute and Recurrent Diabetic Gastroparesis</span> </caption> <col/> <col/> <col/> <thead> <tr class="First Last"> <th class="Lrule Rrule"></th><th align="center" class="Rrule"> Recommended Dosage</th><th align="center" class="Rrule"> Maximum Recommended Daily Dosage</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Elderly patients may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider a lower dosage of 5 mg four times daily with titration to the recommended adult dosage of 10 mg four times daily based upon response and tolerability.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule Rrule">Adult Patients</td><td class="Rrule" rowspan="2">10 mg four times daily (30 minutes before each meal and at bedtime)</td><td align="center" class="Rrule" rowspan="3">40 mg</td> </tr> <tr> <td class="Lrule Rrule">Mild hepatic impairment (Child-Pugh A)</td> </tr> <tr> <td class="Lrule Rrule">Elderly patients <span class="Italics">[see <a href="#LINK_e0253b1c-1443-4e0b-93ce-b65b57950648">Use in Specific Populations (8.5)</a>] </span></td><td class="Rrule">5 mg <a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a> four times daily (30 minutes before each meal and at bedtime) </td> </tr> <tr> <td class="Lrule Rrule">Moderate or severe hepatic impairment (Child-Pugh B or C) <span class="Italics">[see <a href="#LINK_45f3365d-8301-4623-9dad-456f5b35e945">Use in Specific Populations (8.7)</a>] </span></td><td class="Rrule" rowspan="4">5 mg four times daily (30 minutes before each meal and at bedtime)</td><td align="center" class="Rrule" rowspan="4">20 mg</td> </tr> <tr> <td class="Lrule Rrule">CYP2D6 poor metabolizers <span class="Italics">[see <a href="#LINK_ae77abd8-f24e-433a-acd8-4e1b7a7a51fe">Use in Specific Populations (8.9)</a>] </span></td> </tr> <tr> <td class="Lrule Rrule">Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) <span class="Italics">[see <a href="#LINK_7aa57b27-c393-4626-8be0-90d90166bc16">Drug Interactions (7.1)</a>] </span></td> </tr> <tr> <td class="Lrule Rrule">Moderate or severe renal impairment (creatinine clearance less than 60 mL/minute) <span class="Italics">[see <a href="#LINK_187febd7-0621-4747-ad18-ac564f14d966">Use in Specific Populations (8.6)</a>] </span></td> </tr> <tr class="Last"> <td class="Lrule Rrule">Patients with End-Stage Renal Disease (ESRD <span class="Italics">)</span> including those treated with hemodialysis and continuous ambulatory peritoneal dialysis <span class="Italics">[see <a href="#LINK_187febd7-0621-4747-ad18-ac564f14d966">Use in Specific Populations (8.6)</a>] </span></td><td class="Rrule">5 mg twice daily</td><td align="center" class="Rrule">10 mg</td> </tr> </tbody> </table></div>

Oral Solution: 10 mg/10 mL metoclopramide

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Metoclopramide is contraindicated:

{ "type": "p", "children": [], "text": "\nMetoclopramide is contraindicated:\n" }

{ "type": "ul", "children": [ "In patients with a history of tardive dyskinesia (TD) or a dystonic reaction to metoclopramide \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.1, \n \n \n \n \n \n 5.2)]\n \n \n \n \n \n .\n \n \n \n \n \n ", " When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation).", " In patients with pheochromocytoma or other catecholamine-releasing paragangliomas.\n \n \n \n \n \n \nMetoclopramide may cause a hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor \n .\n Metoclopramide may cause a hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.5)]\n \n \n \n \n \n .\n \n \n \n \n \n \n\n", " In patients with epilepsy. Metoclopramide may increase the frequency and severity of seizures \n \n \n \n \n \n [see \n \n \n \n \n \n Adverse Reactions (6)]\n \n \n \n \n \n .\n \n \n \n \n \n ", "In patients with hypersensitivity to metoclopramide. Reactions have included laryngeal and glossal angioedema and bronchospasm \n \n \n \n \n \n [see \n \n \n \n \n \n Adverse Reactions (6)]\n \n \n \n \n \n .\n \n \n \n \n \n " ], "text": "" }

Metoclopramide can cause tardive dyskinesia (TD), a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. The risk of developing TD and the likelihood that TD will become irreversible increases with duration of treatment and total cumulative dosage. Additionally, the risk of developing TD is increased among the elderly, especially elderly women [see Use in Specific Populations (8.5)] , and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with metoclopramide for longer than 12 weeks and reduce the dosage in elderly patients [see Dosage and Administration (2.2, 2.3)].

Discontinue metoclopramide immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn. .Discontinue metoclopramide immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn.

Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Metoclopramide is contraindicated in patients with a history of TD Avoid metoclopramide in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics). Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Metoclopramide is contraindicated in patients with a history of TD [see Contraindications (4)]. Avoid metoclopramide in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).

In addition to TD, metoclopramide may cause other extrapyramidal symptoms (EPS), parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue metoclopramide.

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. Avoid metoclopramide in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics.

Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.

In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.

Management of NMS includes:Management of NMS includes:

Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid metoclopramide use in patients with a history of depression.

Metoclopramide may elevate blood pressure. In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions (7.1)] .

There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Metoclopramide is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [see Contraindications (4)]. Discontinue metoclopramide in any patient with a rapid rise in blood pressure.

Because metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue metoclopramide if any of these adverse reactions occur.

As with other dopamine D 2 receptor antagonists, metoclopramide elevates prolactin levels.

Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, including metoclopramide.Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been 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 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 [see Nonclinical Toxicology (13.1)].

Metoclopramide may impair the mental and/or physical abilities required for the 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 metoclopramide or the interacting drug, depending on the importance of the drug to the patient [see Drug Interactions (7.1)].

The following adverse reactions are described, or described in greater detail, in other sections of the labeling:

{ "type": "p", "children": [], "text": "The following adverse reactions are described, or described in greater detail, in other sections of the labeling:" }

{ "type": "ul", "children": [ "Tardive dyskinesia \n \n \n \n \n \n [see \n \n \n \n \n \n Boxed Warning and \n \n \n \n \n \n Warnings and Precautions (5.1)]\n \n \n \n \n \n \n", "Other extrapyramidal effects \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.2)]\n \n \n \n \n \n \n", "Neuroleptic malignant syndrome \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.3)]\n \n \n \n \n \n \n", "Depression \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.4)]\n \n \n \n \n \n \n", "Hypertension \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.5)]\n \n \n \n \n \n \n", "Fluid retention \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.6)]\n \n \n \n \n \n \n", "Hyperprolactinemia \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.7)]\n \n \n \n \n \n \n", "Effects on the ability to drive and operate machinery \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.8)]\n \n \n \n \n \n \n" ], "text": "" }

The following adverse reactions have been identified from clinical studies or postmarketing reports of metoclopramide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions have been identified from clinical studies or postmarketing reports of metoclopramide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure." }

The most common adverse reactions (in approximately 10% of patients receiving 10 mg of metoclopramide four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of metoclopramide administration.

{ "type": "p", "children": [], "text": "The most common adverse reactions (in approximately 10% of patients receiving 10 mg of metoclopramide four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of metoclopramide administration." }

Adverse reactions, especially those involving the nervous system, occurred after stopping metoclopramide including dizziness, nervousness, and headaches.

{ "type": "p", "children": [], "text": "Adverse reactions, especially those involving the nervous system, occurred after stopping metoclopramide including dizziness, nervousness, and headaches." }

Central Nervous System Disorders

{ "type": "p", "children": [], "text": "\nCentral Nervous System Disorders\n" }

{ "type": "ul", "children": [ "Tardive dyskinesia, acute dystonic reactions, drug-induced parkinsonism, akathisia, and other extrapyramidal symptoms", "Convulsive seizures", "Hallucinations", "Restlessness, drowsiness, fatigue, and lassitude occurred in approximately 10% of patients who received 10 mg four times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurred less frequently.", "Neuroleptic malignant syndrome, serotonin syndrome (in combination with serotonergic agents)." ], "text": "" }

Endocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia

{ "type": "p", "children": [], "text": "\nEndocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia\n \n\n \n \n\n " }

Cardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention

{ "type": "p", "children": [], "text": "\nCardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention\n \n\n \n \n\n " }

Gastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)

{ "type": "p", "children": [], "text": "\nGastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)\n \n\n \n \n\n " }

Hepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential

{ "type": "p", "children": [], "text": "\nHepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential\n \n\n \n \n\n " }

Renal and Urinary Disorders: Urinary frequency, urinary incontinence

{ "type": "p", "children": [], "text": "\nRenal and Urinary Disorders: Urinary frequency, urinary incontinence\n \n\n \n \n\n " }

Hematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia

{ "type": "p", "children": [], "text": "\nHematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia\n \n\n \n \n\n " }

Hypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edema

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edema\n \n\n \n \n\n " }

Eye Disorders: Visual disturbances

{ "type": "p", "children": [], "text": "\nEye Disorders: Visual disturbances \n \n\n \n \n\n " }

Metabolism Disorders: Porphyria

{ "type": "p", "children": [], "text": "\nMetabolism Disorders: Porphyria\n \n\n \n \n\n " }

Table 3 displays the effects of other drugs on metoclopramide.

<div class="scrollingtable"><table> <caption> <span>Table 3. Effects of Other Drugs on Metoclopramide</span> </caption> <col/> <col/> <thead> <tr class="First Last"> <th class="Lrule Rrule" colspan="2" valign="top"> Antipsychotics</th> </tr> </thead> <tbody> <tr class="First"> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS).</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Avoid concomitant use <span class="Italics">[see <a href="#LINK_ec9be2ce-6e06-47fb-b251-4fadc3414afe">Warnings and Precautions (5.1</a>, <a href="#LINK_f30cdf4e-0bde-4a1d-99cb-998e48c45da0">5.2</a>, <a href="#LINK_8e878b54-db5f-40c5-aa96-569ab322bb4d">5.3)</a>]. </span></td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category Above</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Increased plasma concentrations of metoclopramide; risk of exacerbation of extrapyramidal symptoms <span class="Italics">[see <a href="#LINK_5d5901bf-30d3-4542-921d-1cbfd0bb4be3">Clinical Pharmacology (12.3)</a>]. </span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Reduce the metoclopramide dosage <span class="Italics">[see <a href="#LINK_605fd192-a4c6-452e-a7d3-8166a20520bd">Dosage and Administration (2.2</a>, <a href="#LINK_4eaebdb2-17a9-4850-8176-566842069393">2.3)</a>]. </span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Examples</span></td><td class="Rrule" valign="top">quinidine, bupropion, fluoxetine, and paroxetine</td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Monoamine Oxidase Inhibitors</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Increased risk of hypertension <span class="Italics">[see <a href="#LINK_20c428f2-4997-4473-8920-4057c1102d13">Warnings and Precautions (5.5)</a>]. </span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Avoid concomitant use.</td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Central Nervous System (CNS) Depressants</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Increased risk of CNS depression <span class="Italics">[see <a href="#LINK_f04c754c-0774-4fb1-a8ef-9f56e1f3c3e3">Warnings and Precautions (5.8)</a>]. </span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Avoid metoclopramide or the interacting drug, depending on the importance of the drug to the patient.</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Examples</span></td><td class="Rrule" valign="top">alcohol, sedatives, hypnotics, opiates and anxiolytics</td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Drugs that Impair Gastrointestinal Motility</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Decreased systemic absorption of metoclopramide.</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Monitor for reduced therapeutic effect.</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Examples</span></td><td class="Rrule" valign="top">antiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiates</td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Dopaminergic Agonists and Other Drugs that Increase Dopamine Concentrations</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Decreased therapeutic effect of metoclopramide due to opposing effects on dopamine.</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Monitor for reduced therapeutic effect.</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top"><span class="Italics">Examples</span></td><td class="Rrule" valign="top">apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine</td> </tr> </tbody> </table></div>

Table 4 displays the effects of metoclopramide on other drugs.

<div class="scrollingtable"><table> <caption> <span>Table 4. Effects of Metoclopramide on Other Drugs</span> </caption> <col/> <col/> <thead> <tr class="First Last"> <th class="Lrule Rrule" colspan="2" valign="top"> Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>Interaction does not apply to posaconazole delayed-release tablets</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms).</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Avoid concomitant use <span class="Italics">[see <a href="#LINK_f30cdf4e-0bde-4a1d-99cb-998e48c45da0">Warnings and Precautions (5.2)</a>] </span>. </td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Examples</span></td><td class="Rrule" valign="top">Apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotine</td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Succinylcholine, Mivacurium</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Metoclopramide inhibits plasma cholinesterase leading to enhanced neuromuscular blockade.</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Monitor for signs and symptoms of prolonged neuromuscular blockade</td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Drugs with Absorption Altered due to Increased Gastrointestinal Motility</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">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.</td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top"><span class="Underline">Drugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspension <a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a>, fosfomycin) </span>: 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). <br/> <span class="Underline">Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine)</span>: Monitor therapeutic drug concentrations and adjust the dose as needed. See prescribing information for the interacting drug. </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Insulin</span></td> </tr> <tr> <td class="Lrule Rrule" valign="top"><span class="Italics">Clinical Impact</span></td><td class="Rrule" valign="top">Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose.</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top"><span class="Italics">Intervention</span></td><td class="Rrule" valign="top">Monitor blood glucose and adjust insulin dosage regimen as needed.</td> </tr> </tbody> </table></div>

Risk Summary

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 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 estimated 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 the 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 were observed.

Risk Summary

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 [see Data] . Metoclopramide elevates prolactin levels [see Warnings and Precautions (5.7)] ; however, the published data are not adequate to support drug effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for metoclopramide and any potential adverse effects on the breastfed child from metoclopramide or from the underlying maternal condition.

Clinical Considerations

Monitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)] .

Data

In published clinical studies, the estimated amount of metoclopramide received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of metoclopramide received by infants from breast milk ranged from 6 to 24 mcg/kg/day in early puerperium (3 to 9 days postpartum) and from 1 to 13 mcg/kg/day at 8 to 12 weeks postpartum.

Metoclopramide is not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of metoclopramide in pediatric patients have not been established.

Dystonias and other extrapyramidal symptoms associated with metoclopramide are more common in pediatric patients than in adults [see Warnings and Precautions (5.1, 5.2)] . In addition, neonates have reduced levels of NADH-cytochrome b5 reductase, making them more susceptible to methemoglobinemia, a possible adverse reaction of metoclopramide use in neonates [see Use in Specific Populations (8.8)] .

Metoclopramide is known to be substantially excreted by the kidney, and the risk of adverse reactions, including tardive dyskinesia (TD), may be greater in patients with impaired renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] . Elderly patients are more likely to have decreased renal function and may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider a reduced dosage of metoclopramide in elderly patients [see Boxed Warning, Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

The clearance of metoclopramide is decreased and the systemic exposure is increased in patients with moderate to severe renal impairment compared to patients with normal renal function, which may increase the risk of adverse reactions. Reduce the metoclopramide dosage in patients with moderate and severe renal impairment (creatinine clearance less than or equal to 60 mL/minute), including those receiving hemodialysis and continuous ambulatory peritoneal dialysis [see Dosage and Administration (2.2, 2.3), Clinical Pharmacology (12.3)].

Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic metoclopramide clearance (by approximately 50%) compared to patients with normal hepatic function. The resulting increase in metoclopramide blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). Reduce metoclopramide dosage in patients with moderate or severe (Child-Pugh B or C) hepatic impairment [see Dosage and Administration (2.2, 2.3)] . There is no dosage adjustment required for patients with mild hepatic impairment (Child-Pugh A).

In addition, metoclopramide, by producing a transient increase in plasma aldosterone, may increase the risk of fluid retention in patients with hepatic impairment [see Warnings and Precautions (5.6)] .

Monitor patients with hepatic impairment for the occurrence of fluid retention and volume overload.

Metoclopramide-treated patients with NADH-cytochrome b5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia. For patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended. Methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal [see Overdosage (10)].

Metoclopramide is a substrate of CYP2D6. The elimination of metoclopramide may be slowed in patients who are CYP2D6 poor metabolizers (compared to patients who are CYP2D6 intermediate, extensive, or ultra-rapid metabolizers); possibly increasing the risk of dystonic and other adverse reactions to metoclopramide [see Clinical Pharmacology (12.3)]. Reduce the metoclopramide dosage in patients who are poor CYP2D6 metabolizers [see Dosage and Administration (2.2, 2.3)].

Manifestations of metoclopramide overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with metoclopramide use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with metoclopramide overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)].

{ "type": "p", "children": [], "text": "Manifestations of metoclopramide overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with metoclopramide use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with metoclopramide overdose and concomitant treatment with another drug associated with NMS \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.1, \n \n \n \n \n \n 5.2, \n \n \n \n \n \n 5.3)].\n \n \n \n \n \n \n" }

There are no specific antidotes for metoclopramide overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage .

{ "type": "p", "children": [], "text": "There are no specific antidotes for metoclopramide overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage\n \n \n \n \n \n .\n" }

Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal.

{ "type": "p", "children": [], "text": "Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal." }

Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide.

{ "type": "p", "children": [], "text": "Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide." }

Metoclopramide, is a dopamine-2 receptor antagonist. Metoclopramide hydrochloride (metoclopramide monohydrochloride monohydrate) is a white crystalline, odorless substance, freely soluble in water. Its chemical name is 4-amino­5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate.

{ "type": "p", "children": [], "text": "Metoclopramide, is a dopamine-2 receptor antagonist. Metoclopramide hydrochloride (metoclopramide monohydrochloride monohydrate) is a white crystalline, odorless substance, freely soluble in water. Its chemical name is 4-amino­5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate." }

The molecular formula is C 14H 22ClN 3O 2∙HCl∙H 2O. Its molecular weight is 354.3. The structural formula is:

{ "type": "p", "children": [], "text": "The molecular formula is C\n \n \n \n \n \n 14H\n \n \n \n \n \n 22ClN\n \n \n \n \n \n 3O\n \n \n \n \n \n 2∙HCl∙H\n \n \n \n \n \n 2O. Its molecular weight is 354.3. The structural formula is:\n \n\n \n \n\n " }

Metoclopramide Oral Solution USP is an orange-colored, berry-citrus flavored liquid for oral administration and is available in 10 mg/10 mL oral solution.

{ "type": "p", "children": [], "text": "Metoclopramide Oral Solution USP is an orange-colored, berry-citrus flavored liquid for oral administration and is available in 10 mg/10 mL oral solution." }

{ "type": "ul", "children": [ "Each 5 mL (teaspoonful) for oral administration contains: Metoclopramide base (as the monohydrochloride monohydrate) 5 mg. Inactive ingredients: Citric acid, FD&C Yellow No. 6 (Sunset Yellow), flavoring, glycerin, methylparaben, propylparaben, purified water, and sorbitol solution." ], "text": "" }

Metoclopramide stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of metoclopramide in the treatment of gastroesophageal reflux and acute and recurrent diabetic gastroparesis has not been fully established. It seems to sensitize tissues to the action of acetylcholine. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.

Metoclopramide increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.

Gastroesophageal Reflux

In patients with gastroesophageal reflux and low lower esophageal sphincter pressure (LESP), single oral doses of metoclopramide produced dose-related increases in LESP. Effects began at about 5 mg and increased through 20 mg. The increase in LESP from a 5 mg dose lasted about 45 minutes and that of 20 mg lasted between 2 and 3 hours. Increased rate of stomach emptying was observed with single oral doses of 10 mg.

Absorption

Relative to an intravenous dose of 20 mg, the absolute bioavailability of oral metoclopramide is 80% ± 15.5% as demonstrated in a crossover study of 18 subjects. Peak plasma concentrations occurred at about 1 to 2 hours after a single oral dose. Similar time to peak was observed after individual doses at steady state.

In a single dose study of 12 subjects, the area under the drug concentration-time curve increased linearly with doses from 20 to 100 mg (5 times the maximum recommended single dose). Peak concentrations increased linearly with dose; time to peak concentrations remained the same; whole body clearance was unchanged; and the elimination rate remained the same. The mean elimination half-life in subjects with normal renal function was 5 to 6 hours. Linear kinetic processes adequately describe the absorption and elimination of metoclopramide.

Distribution

Metoclopramide is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg), which suggests extensive distribution of drug to the tissues.

Elimination

Metabolism: Metoclopramide undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Dosage and Administration (2.2, 2.3), Use in Specific Populations (8.9)] .

Excretion: Approximately 85% of the radioactivity of an orally administered dose appeared in the urine within 72 hours. After oral administration of 10 or 20 mg, a mean of 18% and 22% of the dose, respectively, was recovered as free metoclopramide in urine within 36 hours.

Specific Populations

Patients with Renal Impairment: In a study of 24 patients with varying degrees of renal impairment (moderate, severe, and end-stage renal disease (ESRD) requiring dialysis), the systemic exposure (AUC) of metoclopramide in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of metoclopramide in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.6)].

Patients with Hepatic Impairment: In a group of 8 patients with severe hepatic impairment (Child-Pugh C), the average metoclopramide clearance was reduced by approximately 50% compared to patients with normal hepatic function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.7)].

Drug Interaction Studies

Effect of Metoclopramide on CYP2D6 Substrates

Although in vitro studies suggest that metoclopramide can inhibit CYP2D6, metoclopramide is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.

Effect of CYP2D6 Inhibitors on Metoclopramide

In healthy subjects, 20 mg of metoclopramide and 60 mg of fluoxetine (a strong CYP2D6 inhibitor) were administered, following prior exposure to 60 mg fluoxetine orally for 8 days. The patients who received concomitant metoclopramide and fluoxetine had a 40% and 90% increase in metoclopramide C max and AUC 0-∞, respectively, compared to patients who received metoclopramide alone (see Table 5) [see Drug Interactions (7.1)] .

<div class="scrollingtable"><table> <caption> <span>Table 5. Metoclopramide Pharmacokinetic Parameters in Healthy Subjects with and without Fluoxetine</span> </caption> <col/> <col/> <col/> <thead> <tr class="First Last"> <th class="Lrule Rrule"> Parameter</th><th align="center" class="Rrule" valign="top"> Metoclopramide alone <br/>(mean ± SD) </th><th align="center" class="Rrule" valign="top"> Metoclopramide with fluoxetine <br/>(mean ± SD) </th> </tr> </thead> <tbody> <tr class="First"> <td class="Lrule Rrule" valign="top">C <span class="Sub">max</span> (ng/mL) </td><td align="center" class="Rrule" valign="top">44 ±15</td><td align="center" class="Rrule" valign="top">62.7 ± 9.2</td> </tr> <tr> <td class="Lrule Rrule" valign="top">AUC <span class="Sub">0-∞</span> (ngˑh/mL) </td><td align="center" class="Rrule" valign="top">313 ± 113</td><td align="center" class="Rrule" valign="top">591 ± 140</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">t <span class="Sub">1/2</span> (h) </td><td align="center" class="Rrule" valign="top">5.5 ± 1.1</td><td align="center" class="Rrule" valign="top">8.5 ± 2.2</td> </tr> </tbody> </table></div>

Carcinogenesis

A 77-week study was conducted in rats with oral metoclopramide doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Metoclopramide elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of metoclopramide [see Warnings and Precautions (5.7)]. In a rat model for assessing the tumor promotion potential, a 2-week oral treatment with metoclopramide at a dose of 260 mg/kg/day (about 35 times the maximum recommended human dose based on body surface area) enhanced the tumorigenic effect of N-nitrosodiethylamine.

Mutagenesis

Metoclopramide was positive in the in vitro Chinese hamster lung cell/HGPRT forward mutation assay for mutagenic effects and in the in vitro human lymphocyte chromosome aberration assay for clastogenic effects. It was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis assay with rat and human hepatocytes, and the in vivo rat micronucleus assay.

Impairment of Fertility

Metoclopramide at intramuscular doses up to 20 mg/kg/day (about three times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

STORAGE

Dispense in a tight, light-resistant container. Store at controlled room temperature between 20°C to 25°C (68°F to 77°F).

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide)." }

Inform patients or their caregivers that metoclopramide can cause serious adverse reactions. Instruct patients to discontinue metoclopramide and contact a healthcare provider immediately if the following serious reactions occur:

{ "type": "p", "children": [], "text": "Inform patients or their caregivers that metoclopramide can cause serious adverse reactions. Instruct patients to discontinue metoclopramide and contact a healthcare provider immediately if the following serious reactions occur:" }

{ "type": "ul", "children": [ "Tardive dyskinesia and other extrapyramidal reactions \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.1, \n \n \n \n \n \n 5.2)]\n \n \n \n \n \n \n", "Neuroleptic malignant syndrome \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.3)]\n \n \n \n \n \n \n", "Depression and/or possible suicidal ideation \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.4)]\n \n \n \n \n \n \n" ], "text": "" }

Inform patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression [see Drug Interactions (7.1, 7.2)] . Explain that the prescriber of any other medication must be made aware that the patient is taking metoclopramide.

{ "type": "p", "children": [], "text": "Inform patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression \n \n \n \n \n \n [see \n \n \n \n \n \n Drug Interactions (7.1, \n \n \n \n \n \n 7.2)]\n \n \n \n \n \n . Explain that the prescriber of any other medication must be made aware that the patient is taking metoclopramide.\n \n\n \n \n\n " }

Inform patients or their caregivers that metoclopramide can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle [see Warnings and Precautions (5.8)] .

{ "type": "p", "children": [], "text": "Inform patients or their caregivers that metoclopramide can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle \n \n \n \n \n \n [see \n \n \n \n \n \n Warnings and Precautions (5.8)]\n \n \n \n \n \n .\n \n\n \n \n\n " }

MANUFACTURED BY Pharmaceutical Associates, Inc. Greenville, SC 29605 www.paipharma.com

{ "type": "p", "children": [], "text": "\nMANUFACTURED BY\n \n \n \n \n \n \nPharmaceutical\n \n \n \n \n \n Associates, Inc.\n \n \n \n \n \n \nGreenville, SC 29605\n \n \n \n \n \n www.paipharma.com\n \n\n \n \n\n " }

R02/22

{ "type": "p", "children": [], "text": "R02/22" }

<div class="scrollingtable"><table> <col/> <col/> <tfoot> <tr class="First Last"> <td valign="top">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align="right" valign="top">Revised: September 2017</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">MEDICATION GUIDE</span> <br/>Metoclopramide (met-o-KLO-pra-mide) Oral Solution USP </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top">Read this Medication Guide before you start taking Metoclopramide and each time you get a refill. There may be new information. If you take another product that contains metoclopramide (such as REGLAN injection, REGLAN orally disintegrating tablets, or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about Metoclopramide?</span> </p> <span class="Bold">Metoclopramide can cause serious side effects, including: <br/> Tardive dyskinesia (abnormal muscle movements). </span>These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping Metoclopramide. There is no treatment for tardive dyskinesia, but symptoms may decrease or go away over time after you stop taking Metoclopramide. <br/>Your chances for getting tardive dyskinesia increase: <ul class="Disk"> <li>the longer you take Metoclopramide and the more Metoclopramide you take. You should not take Metoclopramide for more than 12 weeks.</li> <li>if you are older, especially if you are an older woman.</li> <li>if you have diabetes.</li> </ul>It is not possible for your healthcare provider to know if <span class="Bold">you </span>will get tardive dyskinesia if you take Metoclopramide. Call your healthcare provider right away if you get movements you cannot stop or control, such as: <ul class="Disk"> <li>lip smacking, chewing, or puckering up your mouth</li> <li>frowning or scowling</li> <li>sticking out your tongue</li> <li>blinking and moving your eyes</li> <li>shaking of your arms and legs</li> </ul> See the section <span class="Bold">" What are the possible side effects of Metoclopramide?" </span>for more information about side effects. </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">What is Metoclopramide?</span> <br/> Metoclopramide is a prescription medicine used in adults: <ul class="Disk"> <li>for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.</li> <li>to relieve the symptoms of slow stomach emptying in people with diabetes.</li> </ul> Metoclopramide is not recommended for use in children. </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Do not take Metoclopramide if you:</span> <ul class="Disk"> <li>have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking Metoclopramide or a medicine that works like Metoclopramide.</li> <li>have stomach or intestine problems that could get worse with Metoclopramide, such as bleeding, blockage or a tear in the stomach or bowel wall.</li> <li>have a type of tumor that can cause high blood pressure such as pheochromocytoma.</li> <li>have epilepsy (seizures). Metoclopramide can increase your chance for seizures and make them worse.</li> <li>are allergic to metoclopramide. Metoclopramide can cause serious allergic reactions. Stop taking Metoclopramide right away and get emergency help if you have any of these symptoms: <ul class="Circle"> <li> swelling of your tongue, throat, lips, eyes or face.</li> <li> trouble swallowing or breathing.</li> <li> skin rash, hives, sores in your mouth, or skin blisters.</li> </ul> </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">Before taking Metoclopramide, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disk"> <li>have diabetes. Your dose of insulin may need to be changed.</li> <li>had problems controlling your muscle movements after taking any medicine.</li> <li>have Parkinson's disease.</li> <li>have a type of tumor that can cause high blood pressure (pheochromocytoma).</li> <li>have kidney or liver disease.</li> <li>have or had depression or mental illness.</li> <li>have high blood pressure.</li> <li>have heart failure or heart rhythm problems.</li> <li>have breast cancer.</li> <li>drink alcohol.</li> <li>have seizures</li> <li>are pregnant or plan to become pregnant. Metoclopramide may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking Metoclopramide.</li> <li>are breastfeeding or plan to breastfeed. Metoclopramide can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take Metoclopramide or breastfeed.</li> </ul> Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. <br/>Metoclopramide may affect the way other medicines work, and other medicines may affect how Metoclopramide works. Tell your healthcare provider before you start or stop other medicines. <br/> <span class="Bold">Especially tell your healthcare provider if you take:</span> <ul class="Disk"> <li>another medicine that contains metoclopramide, such as REGLAN injection or metoclopramide oral solution</li> <li>a medicine for Parkinson's disease</li> <li>a blood pressure medicine</li> <li>a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI)</li> <li>an anti-psychotic medicine, used to treat mental illness such as schizophrenia</li> <li>insulin</li> <li>medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.</li> </ul> <span class="Bold">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</span></td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">How should I take Metoclopramide?</span> <ul class="Disk"> <li>Take Metoclopramide exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.</li> <li>You should not take Metoclopramide for more than 12 weeks.</li> <li>Take Metoclopramide at least 30 minutes before each meal and at bedtime.</li> <li>If you take too much Metoclopramide, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">What should I avoid while taking Metoclopramide?</span> <ul class="Disk"> <li>Do not drink alcohol while taking Metoclopramide. Alcohol may make some side effects of Metoclopramide worse, such as feeling sleepy.</li> <li>Do not drive, operate machinery, or do other dangerous activities until you know how Metoclopramide affects you. <br/>Metoclopramide may cause sleepiness or dizziness. </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of Metoclopramide?</span> </p> <ul class="Disk"> <li> <span class="Bold">Tardive dyskinesia (abnormal muscle movements). </span>See <span class="Bold">" What is the most important information I need to know about Metoclopramide?" </span> </li> <li> <span class="Bold">Other changes in muscle control and movement, such as:</span> <ul class="Circle"> <li> <span class="Bold">Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). </span>These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age. </li> <li> <span class="Bold">Parkinsonism. </span>Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking Metoclopramide. </li> <li> <span class="Bold">Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia). </span>Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet. </li> </ul> </li> </ul> <ul class="Disk"> <li> <span class="Bold">Neuroleptic Malignant Syndrome (NMS). </span>NMS is a very rare but very serious condition that can happen with Metoclopramide. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating. </li> <li> <span class="Bold">Depression, thoughts about suicide, and suicide. </span>Some people who take Metoclopramide become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken Metoclopramide have ended their own lives (suicide). </li> <li> <span class="Bold">High blood pressure. </span>Metoclopramide can cause your blood pressure to increase. </li> <li> <span class="Bold">Too much body water. </span>People who have certain liver problems or heart failure and take Metoclopramide may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet. </li> <li> <span class="Bold">Increased prolactin. </span>Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking Metoclopramide. </li> </ul> <span class="Bold">Call your healthcare provider and get medical help right away if you:</span> <ul class="Disk"> <li>feel depressed or have thoughts about hurting or killing yourself</li> <li>have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating</li> <li>have muscle movements you cannot stop or control</li> <li>have muscle movements that are new or unusual </li> </ul>The most common side effects of Metoclopramide include: <ul class="Disk"> <li>restlessness</li> <li>drowsiness</li> <li>tiredness</li> <li>lack of energy</li> </ul> You may have more side effects the longer you take Metoclopramide and the more Metoclopramide you take. <br/>You may still have side effects after stopping Metoclopramide. You may have symptoms from stopping Metoclopramide such as headaches, and feeling dizzy or nervous. <br/>Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of Metoclopramide. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">How should I store Metoclopramide?</span> <ul class="Disk"> <li>Store Metoclopramide at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Keep Metoclopramide in the bottle it comes in and away from light. Keep the bottle closed tightly.</li> </ul> <span class="Bold">Keep Metoclopramide and all medicines out of the reach of children.</span></td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">General information about the safe and effective use of Metoclopramide.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Metoclopramide for a condition for which it was not prescribed. Do not give Metoclopramide to other people, even if they have the same symptoms that you have. It may harm them. <br/>You can ask your pharmacist or healthcare provider for information about Metoclopramide that is written for health professionals. </td> </tr> <tr class="Last"> <td class="Lrule Rrule" colspan="2" valign="top"><span class="Bold">What are the ingredients in Metoclopramide? <br/>Active ingredient: </span> metoclopramide <br/> <span class="Bold">Inactive ingredients: </span>Citric acid, FD&amp;C Yellow No. 6 (Sunset Yellow), flavoring, glycerin, methylparaben, propylparaben, purified water and sorbitol solution. <br/> <span class="Bold">MANUFACTURED BY <br/> <span class="Italics">Pharmaceutical <br/>Associates, Inc. </span></span> <br/>Greenville, SC 29605 <br/>www.paipharma.com <br/> <span class="Bold">R09/17</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<tfoot>\n<tr class=\"First Last\">\n<td valign=\"top\">This Medication Guide has been approved by the U.S. Food and Drug Administration</td><td align=\"right\" valign=\"top\">Revised: September 2017</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">MEDICATION GUIDE</span>\n<br/>Metoclopramide (met-o-KLO-pra-mide) Oral Solution USP\n \n \n \n \n \n </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">Read this Medication Guide before you start taking Metoclopramide and each time you get a refill. There may be new information. If you take another product that contains metoclopramide (such as REGLAN injection, REGLAN orally disintegrating tablets, or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about Metoclopramide?</span>\n</p>\n<span class=\"Bold\">Metoclopramide can cause serious side effects, including:\n \n \n \n \n \n <br/>\t\t\t\t\t\tTardive dyskinesia (abnormal muscle movements). \n \n \n \n \n \n </span>These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping Metoclopramide. There is no treatment for tardive dyskinesia, but symptoms may decrease or go away over time after you stop taking Metoclopramide.\n \n \n \n \n \n <br/>Your chances for getting tardive dyskinesia increase: \t\t\t\t\t\t\n \n \n \n \n \n <ul class=\"Disk\">\n<li>the longer you take Metoclopramide and the more Metoclopramide you take. You should not take Metoclopramide for more than 12 weeks.</li>\n<li>if you are older, especially if you are an older woman.</li>\n<li>if you have diabetes.</li>\n</ul>It is not possible for your healthcare provider to know if \n \n \n \n \n \n <span class=\"Bold\">you </span>will get tardive dyskinesia if you take Metoclopramide. Call your healthcare provider right away if you get movements you cannot stop or control, such as: \t\t\t\t\t\t\n \n \n \n \n \n <ul class=\"Disk\">\n<li>lip smacking, chewing, or puckering up your mouth</li>\n<li>frowning or scowling</li>\n<li>sticking out your tongue</li>\n<li>blinking and moving your eyes</li>\n<li>shaking of your arms and legs</li>\n</ul>\t\t\t\t\t\tSee the section \n \n \n \n \n \n <span class=\"Bold\">\"\n \n \n \n \n \n What are the possible side effects of Metoclopramide?\" \n \n \n \n \n \n </span>for more information about side effects. \t\t\t\t\t\t\t\t\t\n \n \n \n \n \n </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">What is Metoclopramide?</span>\n<br/>\t\t\t\t\tMetoclopramide is a prescription medicine used in adults: \t\t\t\t\t\t\t\t\t\n \n \n \n \n \n <ul class=\"Disk\">\n<li>for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.</li>\n<li>to relieve the symptoms of slow stomach emptying in people with diabetes.</li>\n</ul>\t\t\t\t\t\t\t\t\tMetoclopramide is not recommended for use in children. \t\t\t\t\t\t\t\t\t\n \n \n \n \n \n </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">Do not take Metoclopramide if you:</span>\n<ul class=\"Disk\">\n<li>have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking Metoclopramide or a medicine that works like Metoclopramide.</li>\n<li>have stomach or intestine problems that could get worse with Metoclopramide, such as bleeding, blockage or a tear in the stomach or bowel wall.</li>\n<li>have a type of tumor that can cause high blood pressure such as pheochromocytoma.</li>\n<li>have epilepsy (seizures). Metoclopramide can increase your chance for seizures and make them worse.</li>\n<li>are allergic to metoclopramide. Metoclopramide can cause serious allergic reactions. Stop taking Metoclopramide right away and get emergency help if you have any of these symptoms: \t\t\t\t\t\t\n \n \n \n \n \n <ul class=\"Circle\">\n<li> swelling of your tongue, throat, lips, eyes or face.</li>\n<li> trouble swallowing or breathing.</li>\n<li> skin rash, hives, sores in your mouth, or skin blisters.</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">Before taking Metoclopramide, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disk\">\n<li>have diabetes. Your dose of insulin may need to be changed.</li>\n<li>had problems controlling your muscle movements after taking any medicine.</li>\n<li>have Parkinson's disease.</li>\n<li>have a type of tumor that can cause high blood pressure (pheochromocytoma).</li>\n<li>have kidney or liver disease.</li>\n<li>have or had depression or mental illness.</li>\n<li>have high blood pressure.</li>\n<li>have heart failure or heart rhythm problems.</li>\n<li>have breast cancer.</li>\n<li>drink alcohol.</li>\n<li>have seizures</li>\n<li>are pregnant or plan to become pregnant. Metoclopramide may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking Metoclopramide.</li>\n<li>are breastfeeding or plan to breastfeed. Metoclopramide can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take Metoclopramide or breastfeed.</li>\n</ul>\t\t\t\t\t\t\t\t\tTell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.\n \n \n \n \n \n <br/>Metoclopramide may affect the way other medicines work, and other medicines may affect how Metoclopramide works. Tell your healthcare provider before you start or stop other medicines.\n \n \n \n \n \n <br/>\n<span class=\"Bold\">Especially tell your healthcare provider if you take:</span>\n<ul class=\"Disk\">\n<li>another medicine that contains metoclopramide, such as REGLAN injection or metoclopramide oral solution</li>\n<li>a medicine for Parkinson's disease</li>\n<li>a blood pressure medicine</li>\n<li>a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI)</li>\n<li>an anti-psychotic medicine, used to treat mental illness such as schizophrenia</li>\n<li>insulin</li>\n<li>medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.</li>\n</ul>\n<span class=\"Bold\">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">How should I take Metoclopramide?</span>\n<ul class=\"Disk\">\n<li>Take Metoclopramide exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.</li>\n<li>You should not take Metoclopramide for more than 12 weeks.</li>\n<li>Take Metoclopramide at least 30 minutes before each meal and at bedtime.</li>\n<li>If you take too much Metoclopramide, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">What should I avoid while taking Metoclopramide?</span>\n<ul class=\"Disk\">\n<li>Do not drink alcohol while taking Metoclopramide. Alcohol may make some side effects of Metoclopramide worse, such as feeling sleepy.</li>\n<li>Do not drive, operate machinery, or do other dangerous activities until you know how Metoclopramide affects you.\n \n \n \n \n \n <br/>Metoclopramide may cause sleepiness or dizziness.\n \n \n \n \n \n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of Metoclopramide?</span>\n</p>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Tardive dyskinesia (abnormal muscle movements). </span>See \n \n \n \n \n \n <span class=\"Bold\">\"\n \n \n \n \n \n What is the most important information I need to know about Metoclopramide?\"\n \n \n \n \n \n </span>\n</li>\n<li>\n<span class=\"Bold\">Other changes in muscle control and movement, such as:</span>\n<ul class=\"Circle\">\n<li>\n<span class=\"Bold\">Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). </span>These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age.\n \n \n \n \n \n </li>\n<li>\n<span class=\"Bold\">Parkinsonism. </span>Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking Metoclopramide.\n \n \n \n \n \n </li>\n<li>\n<span class=\"Bold\">Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia). </span>Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet.\n \n \n \n \n \n </li>\n</ul>\n</li>\n</ul>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Neuroleptic Malignant Syndrome (NMS). </span>NMS is a very rare but very serious condition that can happen with Metoclopramide. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.\n \n \n \n \n \n </li>\n<li>\n<span class=\"Bold\">Depression, thoughts about suicide, and suicide. </span>Some people who take Metoclopramide become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken Metoclopramide have ended their own lives (suicide).\n \n \n \n \n \n </li>\n<li>\n<span class=\"Bold\">High blood pressure. </span>Metoclopramide can cause your blood pressure to increase.\n \n \n \n \n \n </li>\n<li>\n<span class=\"Bold\">Too much body water. </span>People who have certain liver problems or heart failure and take Metoclopramide may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet.\n \n \n \n \n \n </li>\n<li>\n<span class=\"Bold\">Increased prolactin. </span>Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking Metoclopramide.\n \n \n \n \n \n </li>\n</ul>\n<span class=\"Bold\">Call your healthcare provider and get medical help right away if you:</span>\n<ul class=\"Disk\">\n<li>feel depressed or have thoughts about hurting or killing yourself</li>\n<li>have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating</li>\n<li>have muscle movements you cannot stop or control</li>\n<li>have muscle movements that are new or unusual </li>\n</ul>The most common side effects of Metoclopramide include:\t\t\n \n \n \n \n \n <ul class=\"Disk\">\n<li>restlessness</li>\n<li>drowsiness</li>\n<li>tiredness</li>\n<li>lack of energy</li>\n</ul>\t\t\t\tYou may have more side effects the longer you take Metoclopramide and the more Metoclopramide you take.\n \n \n \n \n \n <br/>You may still have side effects after stopping Metoclopramide. You may have symptoms from stopping Metoclopramide such as headaches, and feeling dizzy or nervous.\n \n \n \n \n \n <br/>Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of Metoclopramide. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. \t\t\t\t\t\t\t\t\t\n \n \n \n \n \n </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">How should I store Metoclopramide?</span>\n<ul class=\"Disk\">\n<li>Store Metoclopramide at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Keep Metoclopramide in the bottle it comes in and away from light. Keep the bottle closed tightly.</li>\n</ul>\n<span class=\"Bold\">Keep Metoclopramide and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">General information about the safe and effective use of Metoclopramide.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Metoclopramide for a condition for which it was not prescribed. Do not give Metoclopramide to other people, even if they have the same symptoms that you have. It may harm them.\n \n \n \n \n \n <br/>You can ask your pharmacist or healthcare provider for information about Metoclopramide that is written for health professionals. \t\t\t\t\t\t\t\t\t\n \n \n \n \n \n </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\">What are the ingredients in Metoclopramide?\n \n \n \n \n \n <br/>Active ingredient:\n \n \n \n \n \n </span> metoclopramide\n \n \n \n \n \n <br/>\n<span class=\"Bold\">Inactive ingredients: </span>Citric acid, FD&amp;C Yellow No. 6 (Sunset Yellow), flavoring, glycerin, methylparaben, propylparaben, purified water and sorbitol solution.\n \n \n \n \n \n <br/>\n<span class=\"Bold\">MANUFACTURED BY\n \n \n \n \n \n <br/>\n<span class=\"Italics\">Pharmaceutical\n \n \n \n \n \n <br/>Associates, Inc.\n \n \n \n \n \n </span></span>\n<br/>Greenville, SC 29605\n \n \n \n \n \n <br/>www.paipharma.com\n \n \n \n \n \n <br/>\n<span class=\"Bold\">R09/17</span></td>\n</tr>\n</tbody>\n</table></div>" }

NDC 0121-0576-16

{ "type": "p", "children": [], "text": "NDC 0121-0576-16" }

Metoclopramide Oral Solution USP

{ "type": "p", "children": [], "text": "\nMetoclopramide\n \n \n \n \n \n Oral Solution USP\n \n \n \n \n \n \n" }

5 mg/5 mL*

{ "type": "p", "children": [], "text": "\n5 mg/5 mL*\n" }

*Each 5 mL (1 teaspoonful) contains: Metoclopramide 5 mg (present as the hydrochloride)

{ "type": "p", "children": [], "text": "*Each 5 mL (1 teaspoonful) contains:\n \n \n \n \n \n Metoclopramide 5 mg\n \n \n \n \n \n (present as the hydrochloride)\n \n\n \n \n\n " }

PHARMACIST: Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "\nPHARMACIST: Dispense the accompanying\n \n \n \n \n \n Medication Guide to each patient.\n \n \n \n \n \n \n" }

Rx ONLY

{ "type": "p", "children": [], "text": "\nRx ONLY\n" }

16 fl oz (473 mL)

{ "type": "p", "children": [], "text": "\n16 fl oz (473 mL)\n" }

Pharmaceutical Associates, Inc. Greenville, SC 29605

{ "type": "p", "children": [], "text": "\nPharmaceutical\n \n \n \n \n \n Associates, Inc.\n \n \n \n \n \n \nGreenville, SC 29605\n \n\n \n \n\n " }

D elivers 10 mL NDC 0121-1576-10

{ "type": "p", "children": [], "text": "D\n \n \n elivers 10 mL\n\nNDC 0121-1576-10\n" }

Delivers 10 mL

{ "type": "p", "children": [], "text": "\nDelivers 10 mL\n\n" }

NDC 0121-1576-10

{ "type": "p", "children": [], "text": "NDC 0121-1576-10\n \n\n " }

Metoclopramide Oral Solution USP

{ "type": "p", "children": [], "text": "Metoclopramide Oral Solution USP" }

10 mg/10 mL

{ "type": "p", "children": [], "text": "10 mg/10 mL" }

(present as the hydrochloride)

{ "type": "p", "children": [], "text": "(present as the hydrochloride)" }

Package Not Child-Resistant

{ "type": "p", "children": [], "text": "Package Not Child-Resistant " }

PHARMACEUTICAL ASSOCIATES, INC. GREENVILLE, SC 29605

{ "type": "p", "children": [], "text": "PHARMACEUTICAL ASSOCIATES, INC. \n \n \n GREENVILLE, SC 29605\n \n\n " }

Rx ONLY

{ "type": "p", "children": [], "text": "Rx ONLY" }

F1576101021

{ "type": "p", "children": [], "text": "F1576101021" }

Metoclopramide tablets are indicated for the:

{ "type": "p", "children": [], "text": "Metoclopramide tablets are indicated for the:" }

{ "type": "ul", "children": [ "Treatment for 4 to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy.", "Relief of symptoms in adults with acute and recurrent diabetic gastroparesis." ], "text": "" }

Limitations of Use:

{ "type": "p", "children": [], "text": "\nLimitations of Use:\n" }

Metoclopramide tablets are not recommended for use in pediatric patients due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates [see Use in Specific Populations (8.4)].

{ "type": "p", "children": [], "text": "Metoclopramide tablets are not recommended for use in pediatric patients due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates [see Use in Specific Populations (8.4)]." }

Avoid treatment with metoclopramide for longer than 12 weeks because of the increased risk of developing TD with longer-term use [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

Metoclopramide tablets may be administered continuously or intermittently in patients with symptomatic gastroesophageal reflux who fail to respond to conventional therapy:

Continuous Dosing

The recommended adult dosage of metoclopramide is 10 to 15 mg four times daily for 4 to 12 weeks. The treatment duration is determined by endoscopic response. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 60 mg.

Table 1 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

Intermittent Dosing

If symptoms only occur intermittently or at specific times of the day, administer metoclopramide in single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1.

<div class="scrollingtable"><table> <caption> <span>Table 1. Recommended Metoclopramide Tablet Dosage in Patients with Gastroesophageal Reflux</span> </caption> <col/> <col/> <col/> <tfoot> <tr class="First Last"> <td colspan="3"><span class="Sup">1</span> Elderly patients may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider a lower starting dosage of  5 mg four times daily with titration to the recommended adult dosage of 10 to 15 mg four times daily based upon response and tolerability.<br/> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td> <p class="First"> <span class="Bold">Recommended Dosage</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Maximum Recommended Daily Dosage</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Adult patients</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">10 to 15 mg four times daily (thirty minutes before each meal and at bedtime)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">60 mg</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mild hepatic impairment (Child-Pugh A)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Elderly patients [see Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_2bae086a-70ad-4529-9edc-8277c90ab417">8.5</a>)]</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5 mg<span class="Sup">1</span> four times daily (thirty minutes before each meal and at bedtime)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Moderate or severe hepatic impairment (Child-Pugh B or C) [see <span class="Italics">Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_6fda210f-858a-4a1d-bfde-2fa58f9f3f72">8.7</a></span>)]</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="4"> <p class="First">5 mg four times daily (thirty minutes before each meal and at bedtime), or</p> <p>10 mg taken three times daily</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="4"> <p class="First">30 mg</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">CYP2D6 poor metabolizers [see <span class="Italics">Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_1b7feca1-9a25-4d56-80be-73c3f937569e">8.9</a></span>)]</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see <span class="Italics">Drug Interactions (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_44f9fa52-ba76-4556-ad63-5e7e88fce901">7.1</a>)]</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) [see <span class="Italics">Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_64c492bb-033d-4a2d-a37e-5d536ac98967">8.6</a></span>)]</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see<span class="Italics"> Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_64c492bb-033d-4a2d-a37e-5d536ac98967">8.6</a>)]</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5 mg four times daily (thirty minutes before each meal and at bedtime) or 10 mg twice daily</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">20 mg</p> </td> </tr> </tbody> </table></div>

The recommended adult dosage for the treatment of acute and recurrent diabetic gastroparesis is 10 mg four times daily for 2 to 8 weeks, depending on symptomatic response. Avoid metoclopramide treatment for greater than 12 weeks [see Warnings and Precautions (5.1)]. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 40 mg.

Table 2 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

If patients with diabetic gastroparesis have severe nausea or vomiting and are unable to take oral metoclopramide tablets, consider starting therapy with metoclopramide injection given intramuscularly or intravenously for up to 10 days (see the prescribing information for metoclopramide injection). After patients are able to take oral therapy, switch to metoclopramide tablets.

<div class="scrollingtable"><table> <caption> <span>Table 2. Recommended Metoclopramide Tablet Dosage in Patients with Acute and Recurrent Diabetic Gastroparesis</span> </caption> <col/> <col/> <col/> <tfoot> <tr class="First Last"> <td colspan="3"><span class="Sup">1</span> Elderly patients may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider a lower dosage of 5 mg four times daily with titration to the recommended adult dosage of 10 mg four times daily based upon response and tolerability.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td> <p class="First"> <span class="Bold">Recommended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Maximum Recommended Daily Dosage</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Adult Patients</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">10 mg four times daily (30 minutes before each meal and at bedtime)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="3"> <p class="First">40 mg</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mild hepatic impairment (Child-Pugh A)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Elderly patients [<span class="Italics">see Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_2bae086a-70ad-4529-9edc-8277c90ab417">8.5</a>)]</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5 mg<span class="Sup">1</span> four times daily (30 minutes before each meal and at bedtime)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Moderate or severe hepatic impairment (Child-Pugh B or C) [see <span class="Italics">Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_6fda210f-858a-4a1d-bfde-2fa58f9f3f72">8.7</a>)]</span> </p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="4"> <p class="First">5 mg four times daily (30 minutes before each meal and at bedtime)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="4"> <p class="First">20 mg</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">CYP2D6 poor metabolizers [see <span class="Italics">Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_1b7feca1-9a25-4d56-80be-73c3f937569e">8.9</a>)]</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see<span class="Italics"> Drug Interactions (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_44f9fa52-ba76-4556-ad63-5e7e88fce901">7.1</a>)]</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Moderate or severe renal impairment (creatinine clearance less than 60 mL/minute) [see <span class="Italics">Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_64c492bb-033d-4a2d-a37e-5d536ac98967">8.6</a>)]</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see <span class="Italics">Use in Specific Populations (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_64c492bb-033d-4a2d-a37e-5d536ac98967">8.6</a>)]</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">5 mg twice daily</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">10 mg</p> </td> </tr> </tbody> </table></div>

Tablets:

{ "type": "p", "children": [], "text": "Tablets:" }

{ "type": "ul", "children": [ "5 mg metoclopramide, USP: white, round, unscored, debossed “TV” on one side and “2204” on the other side.", "10 mg metoclopramide, USP: white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side." ], "text": "" }

Metoclopramide is contraindicated:

{ "type": "p", "children": [], "text": "Metoclopramide is contraindicated:" }

{ "type": "ul", "children": [ "In patients with a history of tardive dyskinesia (TD) or a dystonic reaction to metoclopramide [see Warnings and Precautions (5.1, 5.2)].", "When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation).", "In patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Metoclopramide may cause a hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor [see Warnings and Precautions (5.5)].\n", "In patients with epilepsy. Metoclopramide may increase the frequency and severity of seizures [see Adverse Reactions (6)].\n", "In patients with hypersensitivity to metoclopramide. Reactions have included laryngeal and glossal angioedema and bronchospasm [see Adverse Reactions (6)].\n" ], "text": "" }

Metoclopramide can cause tardive dyskinesia (TD), a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. The risk of developing TD and the likelihood that TD will become irreversible increases with duration of treatment and total cumulative dosage. Additionally, the risk of developing TD is increased among the elderly, especially elderly women [see Use in Specific Populations (8.5)], and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with metoclopramide for longer than 12 weeks and reduce the dosage in elderly patients [see Dosage and Administration (2.2, 2.3)].

Discontinue metoclopramide immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn.

Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Metoclopramide is contraindicated in patients with a history of TD [see Contraindications (4)]. Avoid metoclopramide in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).

In addition to TD, metoclopramide may cause other extrapyramidal symptoms (EPS), parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue metoclopramide.

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. Avoid metoclopramide in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics.

Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.

In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.

Management of NMS includes:

Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid metoclopramide use in patients with a history of depression.

Metoclopramide may elevate blood pressure. In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions (7.1)].

There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Metoclopramide is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [see Contraindications (4)]. Discontinue metoclopramide in any patient with a rapid rise in blood pressure.

Because metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue metoclopramide if any of these adverse reactions occur.

As with other dopamine D2 receptor antagonists, metoclopramide elevates prolactin levels. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been 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 [see Nonclinical Toxicology (13.1)].

Metoclopramide may impair the mental and/or physical abilities required for the 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 metoclopramide or the interacting drug, depending on the importance of the drug to the patient [see Drug Interactions (7.1)].

The following adverse reactions are described, or described in greater detail, in other sections of the labeling:

{ "type": "p", "children": [], "text": "The following adverse reactions are described, or described in greater detail, in other sections of the labeling:" }

{ "type": "ul", "children": [ "Tardive dyskinesia [see Boxed Warning and Warnings and Precautions (5.1)]\n", "Other extrapyramidal effects [see Warnings and Precautions (5.2)]\n", "Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]\n", "Depression [see Warnings and Precautions (5.4)]\n", "Hypertension [see Warnings and Precautions (5.5)]\n", "Fluid retention [see Warnings and Precautions (5.6)]\n", "Hyperprolactinemia [see Warnings and Precautions (5.7)]\n", "Effects on the ability to drive and operate machinery [see Warnings and Precautions (5.8)]\n" ], "text": "" }

The following adverse reactions have been identified from clinical studies or postmarketing reports of metoclopramide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions have been identified from clinical studies or postmarketing reports of metoclopramide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure." }

The most common adverse reactions (in approximately 10% of patients receiving 10 mg of metoclopramide four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of metoclopramide administration.

{ "type": "p", "children": [], "text": "The most common adverse reactions (in approximately 10% of patients receiving 10 mg of metoclopramide four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of metoclopramide administration." }

Adverse reactions, especially those involving the nervous system, occurred after stopping metoclopramide including dizziness, nervousness, and headaches.

{ "type": "p", "children": [], "text": "Adverse reactions, especially those involving the nervous system, occurred after stopping metoclopramide including dizziness, nervousness, and headaches." }

Central Nervous System Disorders

{ "type": "p", "children": [], "text": "\nCentral Nervous System Disorders\n" }

{ "type": "ul", "children": [ "Tardive dyskinesia, acute dystonic reactions, drug-induced parkinsonism, akathisia, and other extrapyramidal symptoms", "Convulsive seizures", "Hallucinations", "Restlessness, drowsiness, fatigue, and lassitude occurred in approximately 10% of patients who received 10 mg four times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurred less frequently.", "Neuroleptic malignant syndrome, serotonin syndrome (in combination with serotonergic agents)." ], "text": "" }

Endocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia

{ "type": "p", "children": [], "text": "\nEndocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia" }

Cardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention

{ "type": "p", "children": [], "text": "\nCardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention" }

Gastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)

{ "type": "p", "children": [], "text": "\nGastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)" }

Hepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential

{ "type": "p", "children": [], "text": "\nHepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential" }

Renal and Urinary Disorders: Urinary frequency, urinary incontinence

{ "type": "p", "children": [], "text": "\nRenal and Urinary Disorders: Urinary frequency, urinary incontinence" }

Hematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia

{ "type": "p", "children": [], "text": "\nHematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia" }

Hypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edema

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edema" }

Eye Disorders: Visual disturbances

{ "type": "p", "children": [], "text": "\nEye Disorders: Visual disturbances" }

Metabolism Disorders: Porphyria

{ "type": "p", "children": [], "text": "\nMetabolism Disorders: Porphyria" }

Table 3 displays the effects of other drugs on metoclopramide.

<div class="scrollingtable"><table> <caption> <span>Table 3. Effects of Other Drugs on Metoclopramide</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Antipsychotics</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS).</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Avoid concomitant use [see <span class="Italics">Warnings and Precautions (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_76be5b69-efdc-4e40-aacd-d5a282e727fe">5.1</a>, <a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_817d912a-c0dc-4858-b9b1-d53570df4dc1">5.2</a>, <a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_8bbbdd8b-c725-4d1d-90ca-0a1ed99dfac1">5.3</a>)].</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category Above</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Increased plasma concentrations of metoclopramide; risk of exacerbation of extrapyramidal symptoms [see<span class="Italics"> Clinical Pharmacology (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_5453211b-ebe2-4b68-a374-315ef9f73610">12.3</a></span>)].</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Reduce the metoclopramide dosage [see <span class="Italics">Dosage and Administration (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_02871d86-f2ce-48ad-bcc3-9cdbb6cda3c3">2.2</a>, <a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_abbd1c38-5f02-45d2-8915-c2f7a2489b09">2.3</a>)].</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">quinidine, bupropion, fluoxetine, and paroxetine</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Monoamine Oxidase Inhibitors</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Increased risk of hypertension [see <span class="Italics">Warnings and Precautions (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_5f4e547a-44e5-4bb9-a2d8-9310bc771ab5">5.5</a>)].</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Avoid concomitant use.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Central Nervous System (CNS) Depressants</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Increased risk of CNS depression [see<span class="Italics"> Warnings and Precautions (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_267c81c1-f21e-4af6-be5e-fff4566b0317">5.8</a>)].</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Avoid metoclopramide or the interacting drug, depending on the importance of the drug to the patient.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">alcohol, sedatives, hypnotics, opiates and anxiolytics</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs that Impair Gastrointestinal Motility</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Decreased systemic absorption of metoclopramide.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor for reduced therapeutic effect.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">antiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiates</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Dopaminergic Agonists and Other Drugs that Increase Dopamine Concentrations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Decreased therapeutic effect of metoclopramide due to opposing effects on dopamine.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor for reduced therapeutic effect.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine</p> </td> </tr> </tbody> </table></div>

Table 4 displays the effects of metoclopramide on other drugs.

<div class="scrollingtable"><table> <caption> <span> </span> </caption> <col/> <col/> <tfoot> <tr class="First Last"> <td colspan="2"> <p class="First">* Interaction does not apply to posaconazole delayed-release tablets</p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms).</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Avoid concomitant use [see <span class="Italics">Warnings and Precautions (<a href="#853a50ff-f7b7-47a8-bb10-83d9129c74e8.xml#ID_817d912a-c0dc-4858-b9b1-d53570df4dc1">5.2</a>)].</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Examples</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotine</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Succinylcholine, Mivacurium</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Metoclopramide inhibits plasma cholinesterase leading to enhanced neuromuscular blockade.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor for signs and symptoms of prolonged neuromuscular blockade</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Drugs with Absorption Altered due to Increased Gastrointestinal Motility</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">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.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Underline">Drugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspension*, fosfomycin):</span> 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).</p> <p> <span class="Underline">Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine):</span> Monitor therapeutic drug concentrations and adjust the dose as needed. See prescribing information for the interacting drug.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Insulin</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Clinical Impact</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Italics">Intervention</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Monitor blood glucose and adjust insulin dosage regimen as needed.</p> </td> </tr> </tbody> </table></div>

Risk Summary

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 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 estimated 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 the 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 were observed.

Risk Summary

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 [see Data]. Metoclopramide elevates prolactin levels [see Warnings and Precautions (5.7)]; however, the published data are not adequate to support drug effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for metoclopramide and any potential adverse effects on the breastfed child from metoclopramide or from the underlying maternal condition.

Clinical Considerations

Monitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].

Data

In published clinical studies, the estimated amount of metoclopramide received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of metoclopramide received by infants from breast milk ranged from 6 to 24 mcg/kg/day in early puerperium (3 to 9 days postpartum) and from 1 to 13 mcg/kg/day at 8 to 12 weeks postpartum.

Metoclopramide is not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of metoclopramide in pediatric patients have not been established.

Dystonias and other extrapyramidal symptoms associated with metoclopramide are more common in pediatric patients than in adults [see Warnings and Precautions (5.1, 5.2)]. In addition, neonates have reduced levels of NADH-cytochrome b5 reductase, making them more susceptible to methemoglobinemia, a possible adverse reaction of metoclopramide use in neonates [see Use in Specific Populations (8.8)].

Metoclopramide is known to be substantially excreted by the kidney, and the risk of adverse reactions, including tardive dyskinesia (TD), may be greater in patients with impaired renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Elderly patients are more likely to have decreased renal function and may be more sensitive to the therapeutic or adverse effects of metoclopramide; therefore, consider a reduced dosage of metoclopramide in elderly patients [see Boxed Warning, Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

The clearance of metoclopramide is decreased and the systemic exposure is increased in patients with moderate to severe renal impairment compared to patients with normal renal function, which may increase the risk of adverse reactions. Reduce the metoclopramide dosage in patients with moderate and severe renal impairment (creatinine clearance less than or equal to 60 mL/minute), including those receiving hemodialysis and continuous ambulatory peritoneal dialysis [see Dosage and Administration (2.2, 2.3), Clinical Pharmacology (12.3)].

Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic metoclopramide clearance (by approximately 50%) compared to patients with normal hepatic function. The resulting increase in metoclopramide blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). Reduce metoclopramide dosage in patients with moderate or severe (Child-Pugh B or C) hepatic impairment [see Dosage and Administration (2.2, 2.3)]. There is no dosage adjustment required for patients with mild hepatic impairment (Child-Pugh A).

In addition, metoclopramide, by producing a transient increase in plasma aldosterone, may increase the risk of fluid retention in patients with hepatic impairment [see Warnings and Precautions (5.6)].

Monitor patients with hepatic impairment for the occurrence of fluid retention and volume overload.

Metoclopramide-treated patients with NADH-cytochrome b5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia. For patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended. Methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal [see Overdosage (10)].

Metoclopramide is a substrate of CYP2D6. The elimination of metoclopramide may be slowed in patients who are CYP2D6 poor metabolizers (compared to patients who are CYP2D6 intermediate, extensive, or ultra-rapid metabolizers); possibly increasing the risk of dystonic and other adverse reactions to metoclopramide [see Clinical Pharmacology (12.3)]. Reduce the metoclopramide dosage in patients who are poor CYP2D6 metabolizers [see Dosage and Administration (2.2, 2.3)].

Manifestations of metoclopramide overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with metoclopramide use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with metoclopramide overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)].

{ "type": "p", "children": [], "text": "Manifestations of metoclopramide overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with metoclopramide use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with metoclopramide overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)]." }

There are no specific antidotes for metoclopramide overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

{ "type": "p", "children": [], "text": "There are no specific antidotes for metoclopramide overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage." }

Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal.

{ "type": "p", "children": [], "text": "Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal." }

Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide.

{ "type": "p", "children": [], "text": "Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of metoclopramide." }

Metoclopramide hydrochloride, USP, the active ingredient of metoclopramide tablets, USP is a dopamine-2 receptor antagonist. Metoclopramide hydrochloride (metoclopramide monohydrochloride monohydrate) is a white or practically white, crystalline, odorless or practically odorless powder. It is very soluble in water, freely soluble in alcohol, sparingly soluble in chloroform and practically insoluble in ether. Chemically, it is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate. Its structural formula is as follows:

{ "type": "p", "children": [], "text": "Metoclopramide hydrochloride, USP, the active ingredient of metoclopramide tablets, USP is a dopamine-2 receptor antagonist. Metoclopramide hydrochloride (metoclopramide monohydrochloride monohydrate) is a white or practically white, crystalline, odorless or practically odorless powder. It is very soluble in water, freely soluble in alcohol, sparingly soluble in chloroform and practically insoluble in ether. Chemically, it is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate. Its structural formula is as follows:" }

C14H22ClN3O2•HCl•H2O        M.W. 354.3

{ "type": "p", "children": [], "text": "\nC14H22ClN3O2•HCl•H2O        M.W. 354.3" }

Metoclopramide tablets, USP are for oral administration. Metoclopramide tablets, USP are available in 5 mg and 10 mg tablets.

{ "type": "p", "children": [], "text": "Metoclopramide tablets, USP are for oral administration. Metoclopramide tablets, USP are available in 5 mg and 10 mg tablets." }

{ "type": "ul", "children": [ "Each metoclopramide tablet, USP 5 mg contains 5 mg metoclopramide (equivalent to 5.91 mg of metoclopramide hydrochloride, USP).", "Each metoclopramide tablet, USP 10 mg contains 10 mg metoclopramide (equivalent to 11.82 mg of metoclopramide hydrochloride, USP)." ], "text": "" }

Inactive Ingredients

{ "type": "p", "children": [], "text": "\nInactive Ingredients\n" }

Corn starch, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.

{ "type": "p", "children": [], "text": "Corn starch, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate." }

Metoclopramide stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of metoclopramide in the treatment of gastroesophageal reflux and acute and recurrent diabetic gastroparesis has not been fully established. It seems to sensitize tissues to the action of acetylcholine. The effect of metoclopramide on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.

Metoclopramide increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.

Gastroesophageal Reflux

In patients with gastroesophageal reflux and low lower esophageal sphincter pressure (LESP), single oral doses of metoclopramide produced dose-related increases in LESP. Effects began at about 5 mg and increased through 20 mg. The increase in LESP from a 5 mg dose lasted about 45 minutes and that of 20 mg lasted between 2 and 3 hours. Increased rate of stomach emptying was observed with single oral doses of 10 mg.

Absorption

Relative to an intravenous dose of 20 mg, the absolute bioavailability of oral metoclopramide is 80% ± 15.5% as demonstrated in a crossover study of 18 subjects. Peak plasma concentrations occurred at about 1 to 2 hours after a single oral dose. Similar time to peak was observed after individual doses at steady state.

In a single dose study of 12 subjects, the area under the drug concentration-time curve increased linearly with doses from 20 to 100 mg (5 times the maximum recommended single dose). Peak concentrations increased linearly with dose; time to peak concentrations remained the same; whole body clearance was unchanged; and the elimination rate remained the same. The mean elimination half-life in subjects with normal renal function was 5 to 6 hours. Linear kinetic processes adequately describe the absorption and elimination of metoclopramide.

Distribution

Metoclopramide is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg), which suggests extensive distribution of drug to the tissues.

Elimination

Metabolism: Metoclopramide undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Dosage and Administration (2.2, 2.3), Use in Specific Populations (8.9)].

Excretion: Approximately 85% of the radioactivity of an orally administered dose appeared in the urine within 72 hours. After oral administration of 10 or 20 mg, a mean of 18% and 22% of the dose, respectively, was recovered as free metoclopramide in urine within 36 hours.

Specific Populations

Patients with Renal Impairment: In a study of 24 patients with varying degrees of renal impairment (moderate, severe, and end-stage renal disease (ESRD) requiring dialysis), the systemic exposure (AUC) of metoclopramide in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of metoclopramide in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.6)].

Patients with Hepatic Impairment: In a group of 8 patients with severe hepatic impairment (Child-Pugh C), the average metoclopramide clearance was reduced by approximately 50% compared to patients with normal hepatic function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.7)].

Drug Interaction Studies

Effect of Metoclopramide on CYP2D6 Substrates

Although in vitro studies suggest that metoclopramide can inhibit CYP2D6, metoclopramide is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.

Effect of CYP2D6 Inhibitors on Metoclopramide

In healthy subjects, 20 mg of metoclopramide and 60 mg of fluoxetine (a strong CYP2D6 inhibitor) were administered, following prior exposure to 60 mg fluoxetine orally for 8 days. The patients who received concomitant metoclopramide and fluoxetine had a 40% and 90% increase in metoclopramide Cmax and AUC0-∞, respectively, compared to patients who received metoclopramide alone (see Table 5) [see Drug Interactions (7.1)].

<div class="scrollingtable"><table> <caption> <span>Table 5. Metoclopramide Pharmacokinetic Parameters in Healthy Subjects with and without Fluoxetine</span> </caption> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Parameter</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Metoclopramide alone<br/> </span>(mean SD)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Metoclopramide with fluoxetine<br/> </span>(mean SD)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">C<span class="Sub">max</span> (ng/mL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">44 ± 15</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">62.7 ± 9.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">AUC<span class="Sub">0-∞ </span>(ng∙h/mL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">313 ± 113</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">591 ± 140</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">t<span class="Sub">1/2</span> (h)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">5.5 ± 1.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">8.5 ± 2.2</p> </td> </tr> </tbody> </table></div>

Carcinogenesis

A 77-week study was conducted in rats with oral metoclopramide doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Metoclopramide elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of metoclopramide [see Warnings and Precautions (5.7)]. In a rat model for assessing the tumor promotion potential, a 2-week oral treatment with metoclopramide at a dose of 260 mg/kg/day (about 35 times the maximum recommended human dose based on body surface area) enhanced the tumorigenic effect of N-nitrosodiethylamine.

Mutagenesis

Metoclopramide was positive in the in vitro Chinese hamster lung cell/HGPRT forward mutation assay for mutagenic effects and in the in vitro human lymphocyte chromosome aberration assay for clastogenic effects. It was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis assay with rat and human hepatocytes, and the in vivo rat micronucleus assay.

Impairment of Fertility

Metoclopramide at intramuscular doses up to 20 mg/kg/day (about three times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

Each white, round, unscored, debossed “TV” on one side and “2204” on the other side, compressed metoclopramide tablet, USP contains metoclopramide hydrochloride, USP equivalent to 5 mg metoclopramide. Available in blistercards of 30 (NDC 0615-7698-39) and Unit-dose boxes of 30 (NDC 0615-7698-30).

{ "type": "p", "children": [], "text": "Each white, round, unscored, debossed “TV” on one side and “2204” on the other side, compressed metoclopramide tablet, USP contains metoclopramide hydrochloride, USP equivalent to 5 mg metoclopramide. Available in blistercards of 30 (NDC 0615-7698-39) and Unit-dose boxes of 30 (NDC 0615-7698-30)." }

Each white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side, compressed metoclopramide tablet, USP contains metoclopramide hydrochloride, USP equivalent to 10 mg metoclopramide. Available in blistercards of 30 (NDC 0615-8285-39) and Unit-dose boxes of 30 (NDC 0615-8285-30).

{ "type": "p", "children": [], "text": "Each white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side, compressed metoclopramide tablet, USP contains metoclopramide hydrochloride, USP equivalent to 10 mg metoclopramide. Available in blistercards of 30 (NDC 0615-8285-39) and Unit-dose boxes of 30 (NDC 0615-8285-30)." }

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. PROTECT FROM LIGHT.

{ "type": "p", "children": [], "text": "Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. PROTECT FROM LIGHT." }

This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.

{ "type": "p", "children": [], "text": "This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed." }

Dispense in a tight, light-resistant container.

{ "type": "p", "children": [], "text": "Dispense in a tight, light-resistant container." }

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

{ "type": "p", "children": [], "text": "KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN." }

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide)." }

Inform patients or their caregivers that metoclopramide can cause serious adverse reactions. Instruct patients to discontinue metoclopramide and contact a healthcare provider immediately if the following serious reactions occur:

{ "type": "p", "children": [], "text": "Inform patients or their caregivers that metoclopramide can cause serious adverse reactions. Instruct patients to discontinue metoclopramide and contact a healthcare provider immediately if the following serious reactions occur:" }

{ "type": "ul", "children": [ "Tardive dyskinesia and other extrapyramidal reactions [see Warnings and Precautions (5.1, 5.2)]", "Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]", "Depression and/or possible suicidal ideation [see Warnings and Precautions (5.4)]\n" ], "text": "" }

Inform patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression [see Drug Interactions (7.1, 7.2)]. Explain that the prescriber of any other medication must be made aware that the patient is taking metoclopramide tablets.

{ "type": "p", "children": [], "text": "Inform patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression [see Drug Interactions (7.1, 7.2)]. Explain that the prescriber of any other medication must be made aware that the patient is taking metoclopramide tablets." }

Inform patients or their caregivers that metoclopramide tablets can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "Inform patients or their caregivers that metoclopramide tablets can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle [see Warnings and Precautions (5.8)].\n" }

Dispense with Medication Guide available at: www.tevausa.com/medguides

{ "type": "p", "children": [], "text": "Dispense with Medication Guide available at: www.tevausa.com/medguides" }

Manufactured In Croatia By:

{ "type": "p", "children": [], "text": "Manufactured In Croatia By:" }

Pliva Hrvatska d.o.o.

{ "type": "p", "children": [], "text": "\nPliva Hrvatska d.o.o.\n" }

Zagreb, Croatia

{ "type": "p", "children": [], "text": "Zagreb, Croatia" }

Manufactured For:

{ "type": "p", "children": [], "text": "Manufactured For:" }

Teva Pharmaceuticals

{ "type": "p", "children": [], "text": "\nTeva Pharmaceuticals\n" }

Parsippany, NJ 07054

{ "type": "p", "children": [], "text": "Parsippany, NJ 07054" }

Rev. R 8/2021

{ "type": "p", "children": [], "text": "Rev. R 8/2021" }

Dispense with Medication Guide available at: www.tevausa.com/medguides

{ "type": "p", "children": [], "text": "Dispense with Medication Guide available at: www.tevausa.com/medguides" }

<div class="scrollingtable"><table> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Read this Medication Guide before you start taking metoclopramide tablets and each time you get a refill. There may be new information. If you take another product that contains metoclopramide (such as metoclopramide injection, metoclopramide orally disintegrating tablets, or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What is the most important information I should know about metoclopramide tablets?</span> </p> <p> <span class="Bold">Metoclopramide tablets can cause serious side effects, including:</span> </p> <p> <span class="Bold">Tardive dyskinesia (abnormal muscle movements). </span>These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping metoclopramide tablets. There is no treatment for tardive dyskinesia, but symptoms may decrease or go away over time after you stop taking metoclopramide tablets.</p> <p>Your chances for getting tardive dyskinesia increase:</p> <ul class="Disk"> <li>the longer you take metoclopramide tablets and the more metoclopramide tablets you take. You should not take metoclopramide tablets for more than 12 weeks.</li> <li>if you are older, especially if you are an older woman.</li> <li>if you have diabetes.</li> </ul> <p>It is not possible for your healthcare provider to know if <span class="Bold">you</span> will get tardive dyskinesia if you take metoclopramide tablets.</p> <p>Call your healthcare provider right away if you get movements you cannot stop or control, such as:</p> <ul class="Disk"> <li>lip smacking, chewing, or puckering up your mouth</li> <li>frowning or scowling</li> <li>sticking out your tongue</li> <li>blinking and moving your eyes</li> <li>shaking of your arms and legs</li> </ul> <p>See the section <span class="Bold">“What are the possible side effects of metoclopramide tablets?” </span>for more information about side effects.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What are metoclopramide tablets?</span> </p> <p>Metoclopramide tablets are a prescription medicine used in adults:</p> <ul class="Disk"> <li>for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.</li> <li>to relieve the symptoms of slow stomach emptying in people with diabetes.</li> </ul> <p>Metoclopramide tablets are not recommended for use in children.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Do not take metoclopramide tablets if you:</span> </p> <ul class="Disk"> <li>have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking metoclopramide tablets or a medicine that works like metoclopramide tablets.</li> <li>have stomach or intestine problems that could get worse with metoclopramide tablets, such as bleeding, blockage or a tear in the stomach or bowel wall.</li> <li>have a type of tumor that can cause high blood pressure such as pheochromocytoma.</li> <li>have epilepsy (seizures). Metoclopramide tablets can increase your chance for seizures and make them worse.</li> <li>are allergic to metoclopramide. Metoclopramide tablets can cause serious allergic reactions. Stop taking metoclopramide tablets right away and get emergency help if you have any of these symptoms:<ul class="Circle"> <li>swelling of your tongue, throat, lips, eyes or face.</li> <li>trouble swallowing or breathing.</li> <li>skin rash, hives, sores in your mouth, or skin blisters.</li> </ul> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Before taking metoclopramide tablets, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <ul class="Disk"> <li>have diabetes. Your dose of insulin may need to be changed.</li> <li>had problems controlling your muscle movements after taking any medicine.</li> <li>have Parkinson’s disease.</li> <li>have a type of tumor that can cause high blood pressure (pheochromoctyoma).</li> <li>have kidney or liver disease.</li> <li>have or had depression or mental illness.</li> <li>have high blood pressure.</li> <li>have heart failure or heart rhythm problems.</li> <li>have breast cancer.</li> <li>drink alcohol.</li> <li>have seizures</li> <li>are pregnant or plan to become pregnant. Metoclopramide tablets may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking metoclopramide tablets.</li> <li>are breastfeeding or plan to breastfeed. Metoclopramide can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take metoclopramide tablets or breastfeed.</li> </ul> <p>Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> <p>Metoclopramide tablets may affect the way other medicines work, and other medicines may affect how metoclopramide tablets work.</p> <p>Tell your healthcare provider before you start or stop other medicines.</p> <p> <span class="Bold">Especially tell your healthcare provider if you take:</span> </p> <ul class="Disk"> <li>another medicine that contains metoclopramide, such as metoclopramide injection or metoclopramide oral solution</li> <li>a medicine for Parkinson’s disease</li> <li>a blood pressure medicine</li> <li>a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI)</li> <li>an anti-psychotic medicine, used to treat mental illness such as schizophrenia</li> <li>insulin</li> <li>medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics</li> </ul> <p>If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.</p> <p> <span class="Bold">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">How should I take metoclopramide tablets?</span> </p> <ul class="Disk"> <li>Take metoclopramide tablets exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.</li> <li>Metoclopramide comes as a tablet you take by mouth.</li> <li>You should not take metoclopramide tablets for more than 12 weeks.</li> <li>Take metoclopramide tablets at least 30 minutes before each meal and at bedtime.</li> <li>If you take too many metoclopramide tablets, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What should I avoid while taking metoclopramide tablets?</span> </p> <ul class="Disk"> <li>Do not drink alcohol while taking metoclopramide tablets. Alcohol may make some side effects of metoclopramide tablets worse, such as feeling sleepy.</li> <li>Do not drive, operate machinery, or do other dangerous activities until you know how metoclopramide tablets affect you. Metoclopramide tablets may cause sleepiness or dizziness.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What are the possible side effects of metoclopramide tablets?</span> </p> <ul class="Disk"> <li> <span class="Bold">Tardive dyskinesia (abnormal muscle movements). See “What is the most important information I need to know about metoclopramide tablets?”</span> </li> <li> <span class="Bold">Other changes in muscle control and movement, such as:</span> <ul class="Circle"> <li> <span class="Bold">Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). </span>These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age.</li> <li> <span class="Bold">Parkinsonism.</span> Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking metoclopramide tablets.</li> <li> <span class="Bold">Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia)</span>. Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet.</li> </ul> </li> <li> <span class="Bold">Neuroleptic Malignant Syndrome (NMS).</span> NMS is a very rare but very serious condition that can happen with metoclopramide tablets. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.</li> <li> <span class="Bold">Depression, thoughts about suicide, and suicide.</span> Some people who take metoclopramide tablets become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken metoclopramide tablets have ended their own lives (suicide).</li> <li> <span class="Bold">High blood pressure. </span>Metoclopramide tablets can cause your blood pressure to increase.</li> <li> <span class="Bold">Too much body water.</span> People who have certain liver problems or heart failure and take metoclopramide tablets may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet.</li> <li> <span class="Bold">Increased prolactin</span>. Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking metoclopramide tablets.</li> </ul> <p> <span class="Bold">Call your healthcare provider and get medical help right away if you:</span> </p> <ul class="Disk"> <li>feel depressed or have thoughts about hurting or killing yourself</li> <li>have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating</li> <li>have muscle movements you cannot stop or control</li> <li>have muscle movements that are new or unusual</li> </ul> <p>The most common side effects of metoclopramide tablets include:</p> <ul class="Disk"> <li>restlessness</li> <li>drowsiness</li> <li>tiredness</li> <li>lack of energy</li> </ul> <p>You may have more side effects the longer you take metoclopramide tablets and the more metoclopramide tablets you take.</p> <p>You may still have side effects after stopping metoclopramide tablets. You may have symptoms from stopping metoclopramide tablets such as headaches, and feeling dizzy or nervous.</p> <p>Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of metoclopramide tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">How should I store metoclopramide tablets?</span> </p> <ul class="Disk"> <li>Store metoclopramide tablets at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Keep metoclopramide tablets in the bottle it comes in and away from light. Keep the bottle closed tightly.</li> </ul> <p> <span class="Bold">Keep metoclopramide tablets and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">General information about the safe and effective use of metoclopramide tablets.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use metoclopramide tablets for a condition for which they were not prescribed. Do not give metoclopramide tablets to other people, even if they have the same symptoms that you have. They may harm them.</p> <p>You can ask your pharmacist or healthcare provider for information about metoclopramide tablets that is written for health professionals. For more information, call 1-888-838-2872.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">What are the ingredients in metoclopramide tablets?</span> </p> <p> <span class="Bold">Active ingredient: </span>metoclopramide hydrochloride</p> <p> <span class="Bold">Inactive ingredients</span>: corn starch, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Manufactured In Croatia By: <span class="Bold">Pliva Hrvatska d.o.o. </span>Zagreb, Croatia<p class="First">Manufactured For: <span class="Bold">Teva Pharmaceuticals, </span>Parsippany, NJ 07054</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Read this Medication Guide before you start taking metoclopramide tablets and each time you get a refill. There may be new information. If you take another product that contains metoclopramide (such as metoclopramide injection, metoclopramide orally disintegrating tablets, or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about metoclopramide tablets?</span>\n</p>\n<p>\n<span class=\"Bold\">Metoclopramide tablets can cause serious side effects, including:</span>\n</p>\n<p>\n<span class=\"Bold\">Tardive dyskinesia (abnormal muscle movements). </span>These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping metoclopramide tablets. There is no treatment for tardive dyskinesia, but symptoms may decrease or go away over time after you stop taking metoclopramide tablets.</p>\n<p>Your chances for getting tardive dyskinesia increase:</p>\n<ul class=\"Disk\">\n<li>the longer you take metoclopramide tablets and the more metoclopramide tablets you take. You should not take metoclopramide tablets for more than 12 weeks.</li>\n<li>if you are older, especially if you are an older woman.</li>\n<li>if you have diabetes.</li>\n</ul>\n<p>It is not possible for your healthcare provider to know if <span class=\"Bold\">you</span> will get tardive dyskinesia if you take metoclopramide tablets.</p>\n<p>Call your healthcare provider right away if you get movements you cannot stop or control, such as:</p>\n<ul class=\"Disk\">\n<li>lip smacking, chewing, or puckering up your mouth</li>\n<li>frowning or scowling</li>\n<li>sticking out your tongue</li>\n<li>blinking and moving your eyes</li>\n<li>shaking of your arms and legs</li>\n</ul>\n<p>See the section <span class=\"Bold\">“What are the possible side effects of metoclopramide tablets?” </span>for more information about side effects.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What are metoclopramide tablets?</span>\n</p>\n<p>Metoclopramide tablets are a prescription medicine used in adults:</p>\n<ul class=\"Disk\">\n<li>for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.</li>\n<li>to relieve the symptoms of slow stomach emptying in people with diabetes.</li>\n</ul>\n<p>Metoclopramide tablets are not recommended for use in children.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Do not take metoclopramide tablets if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking metoclopramide tablets or a medicine that works like metoclopramide tablets.</li>\n<li>have stomach or intestine problems that could get worse with metoclopramide tablets, such as bleeding, blockage or a tear in the stomach or bowel wall.</li>\n<li>have a type of tumor that can cause high blood pressure such as pheochromocytoma.</li>\n<li>have epilepsy (seizures). Metoclopramide tablets can increase your chance for seizures and make them worse.</li>\n<li>are allergic to metoclopramide. Metoclopramide tablets can cause serious allergic reactions. Stop taking metoclopramide tablets right away and get emergency help if you have any of these symptoms:<ul class=\"Circle\">\n<li>swelling of your tongue, throat, lips, eyes or face.</li>\n<li>trouble swallowing or breathing.</li>\n<li>skin rash, hives, sores in your mouth, or skin blisters.</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Before taking metoclopramide tablets, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>have diabetes. Your dose of insulin may need to be changed.</li>\n<li>had problems controlling your muscle movements after taking any medicine.</li>\n<li>have Parkinson’s disease.</li>\n<li>have a type of tumor that can cause high blood pressure (pheochromoctyoma).</li>\n<li>have kidney or liver disease.</li>\n<li>have or had depression or mental illness.</li>\n<li>have high blood pressure.</li>\n<li>have heart failure or heart rhythm problems.</li>\n<li>have breast cancer.</li>\n<li>drink alcohol.</li>\n<li>have seizures</li>\n<li>are pregnant or plan to become pregnant. Metoclopramide tablets may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking metoclopramide tablets.</li>\n<li>are breastfeeding or plan to breastfeed. Metoclopramide can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take metoclopramide tablets or breastfeed.</li>\n</ul>\n<p>Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n<p>Metoclopramide tablets may affect the way other medicines work, and other medicines may affect how metoclopramide tablets work.</p>\n<p>Tell your healthcare provider before you start or stop other medicines.</p>\n<p>\n<span class=\"Bold\">Especially tell your healthcare provider if you take:</span>\n</p>\n<ul class=\"Disk\">\n<li>another medicine that contains metoclopramide, such as metoclopramide injection or metoclopramide oral solution</li>\n<li>a medicine for Parkinson’s disease</li>\n<li>a blood pressure medicine</li>\n<li>a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI)</li>\n<li>an anti-psychotic medicine, used to treat mental illness such as schizophrenia</li>\n<li>insulin</li>\n<li>medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics</li>\n</ul>\n<p>If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.</p>\n<p>\n<span class=\"Bold\">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take metoclopramide tablets?</span>\n</p>\n<ul class=\"Disk\">\n<li>Take metoclopramide tablets exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.</li>\n<li>Metoclopramide comes as a tablet you take by mouth.</li>\n<li>You should not take metoclopramide tablets for more than 12 weeks.</li>\n<li>Take metoclopramide tablets at least 30 minutes before each meal and at bedtime.</li>\n<li>If you take too many metoclopramide tablets, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while taking metoclopramide tablets?</span>\n</p>\n<ul class=\"Disk\">\n<li>Do not drink alcohol while taking metoclopramide tablets. Alcohol may make some side effects of metoclopramide tablets worse, such as feeling sleepy.</li>\n<li>Do not drive, operate machinery, or do other dangerous activities until you know how metoclopramide tablets affect you. Metoclopramide tablets may cause sleepiness or dizziness.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of metoclopramide tablets?</span>\n</p>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Tardive dyskinesia (abnormal muscle movements). See “What is the most important information I need to know about metoclopramide tablets?”</span>\n</li>\n<li>\n<span class=\"Bold\">Other changes in muscle control and movement, such as:</span>\n<ul class=\"Circle\">\n<li>\n<span class=\"Bold\">Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). </span>These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age.</li>\n<li>\n<span class=\"Bold\">Parkinsonism.</span> Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking metoclopramide tablets.</li>\n<li>\n<span class=\"Bold\">Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia)</span>. Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet.</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Neuroleptic Malignant Syndrome (NMS).</span> NMS is a very rare but very serious condition that can happen with metoclopramide tablets. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.</li>\n<li>\n<span class=\"Bold\">Depression, thoughts about suicide, and suicide.</span> Some people who take metoclopramide tablets become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken metoclopramide tablets have ended their own lives (suicide).</li>\n<li>\n<span class=\"Bold\">High blood pressure. </span>Metoclopramide tablets can cause your blood pressure to increase.</li>\n<li>\n<span class=\"Bold\">Too much body water.</span> People who have certain liver problems or heart failure and take metoclopramide tablets may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet.</li>\n<li>\n<span class=\"Bold\">Increased prolactin</span>. Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking metoclopramide tablets.</li>\n</ul>\n<p>\n<span class=\"Bold\">Call your healthcare provider and get medical help right away if you:</span>\n</p>\n<ul class=\"Disk\">\n<li>feel depressed or have thoughts about hurting or killing yourself</li>\n<li>have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating</li>\n<li>have muscle movements you cannot stop or control</li>\n<li>have muscle movements that are new or unusual</li>\n</ul>\n<p>The most common side effects of metoclopramide tablets include:</p>\n<ul class=\"Disk\">\n<li>restlessness</li>\n<li>drowsiness</li>\n<li>tiredness</li>\n<li>lack of energy</li>\n</ul>\n<p>You may have more side effects the longer you take metoclopramide tablets and the more metoclopramide tablets you take.</p>\n<p>You may still have side effects after stopping metoclopramide tablets. You may have symptoms from stopping metoclopramide tablets such as headaches, and feeling dizzy or nervous.</p>\n<p>Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of metoclopramide tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store metoclopramide tablets?</span>\n</p>\n<ul class=\"Disk\">\n<li>Store metoclopramide tablets at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Keep metoclopramide tablets in the bottle it comes in and away from light. Keep the bottle closed tightly.</li>\n</ul>\n<p>\n<span class=\"Bold\">Keep metoclopramide tablets and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of metoclopramide tablets.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use metoclopramide tablets for a condition for which they were not prescribed. Do not give metoclopramide tablets to other people, even if they have the same symptoms that you have. They may harm them.</p>\n<p>You can ask your pharmacist or healthcare provider for information about metoclopramide tablets that is written for health professionals. For more information, call 1-888-838-2872.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in metoclopramide tablets?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient: </span>metoclopramide hydrochloride</p>\n<p>\n<span class=\"Bold\">Inactive ingredients</span>: corn starch, dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">Manufactured In Croatia By: <span class=\"Bold\">Pliva Hrvatska d.o.o. </span>Zagreb, Croatia<p class=\"First\">Manufactured For: <span class=\"Bold\">Teva Pharmaceuticals, </span>Parsippany, NJ 07054</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration.\n" }

Rev. E 8/2021

{ "type": "p", "children": [], "text": "Rev. E 8/2021" }