Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

REGLAN (NDA-017862)

(METOCLOPRAMIDE HYDROCHLORIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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02/09/2026 (SUPPL-64)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: TARDIVE DYSKINESIA

Metoclopramide, including REGLAN Injection, can cause tardive dyskinesia (TD), a potentially irreversible serious movement disorder. In patients treated with metoclopramide, including REGLAN Injection, the risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dosage.
REGLAN Injection is contraindicated in patients with a history of TD.
Immediately discontinue REGLAN Injection in patients who develop signs or symptoms of TD.
In patients with diabetic gastroparesis, avoid a total duration of treatment with metoclopramide products, including REGLAN Injection, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD.
See WARNINGS.

4 Contraindications

Additions and/or revisions underlined:

REGLAN Injection is contraindicated:

in patients with a history of tardive dyskinesia (TD) or a dystonic reaction to metoclopramide. See WARNINGS.
whenever 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.
…

5 Warnings and Precautions

WARNINGS

Additions and/or revisions underlined:

Tardive Dyskinesia (see BOXED WARNING)

Metoclopramide, including REGLAN Injection, 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. Metoclopramide, including REGLAN Injection, may also suppress, or partially suppress, the signs of TD, and may delay the diagnosis of TD because it may mask the underlying disease process. The effect of the symptomatic suppression upon the long-term course of TD is unknown. TD may remit, partially or completely, if treatment with REGLAN Injection is discontinued.

In patients treated with metoclopramide, including REGLAN Injection, 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 in elderly patients, especially in elderly women, and in patients with diabetes mellitus.

Prevention, Mitigation, and Monitoring for TD

REGLAN Injection, contraindicated in patients with history of TD
Avoid use of REGLAN Injection in patients receiving concomitant antipsychotics due to the potential additive effects of TD.
Reduce the dosage of REGLAN Injection in the elderly. (see DOSAGE AND ADMINISTRATION, Renal and Hepatic Impairment).
Immediately discontinue REGLAN Injection immediately in patients who develop signs and symptoms of TD.
In patients with diabetic gastroparesis, avoid a total duration of treatment with metoclopramide products, including REGLAN Injection, for longer than 12 weeks. If longer-term use is unavoidable, routinely monitor for signs and symptoms of TD.
If patients have continued TD symptoms, consider TD treatment.

Other Extrapyramidal Symptoms
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 REGLAN Injection.
Extrapyramidal symptoms (EPS), such as acute dystonic reactions, occurred in patients treated with metoclopramide dosages of 30 mg to 40 mg daily. Such reactions occurred more frequently in adults less than 30 years of age and at the higher dosages used in prophylaxis of vomiting due to cancer chemotherapy. EPS occurred more frequently in pediatric patients compared to adults (REGLAN Injection is only approved in pediatric patients for small bowel intubation). Symptoms can occur in the first 24 to 48 hours after starting metoclopramide. Symptoms included involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions were present as stridor and dyspnea, possibly due to laryngospasm. Diphenhydramine hydrochloride or benztropine mesylate may be used to treat these adverse reactions. Avoid REGLAN Injection in patients receiving other drugs that can cause EPS (e.g., antipsychotics).
Parkinsonian symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like facies), have occurred after starting metoclopramide, more commonly within the first 6 months, but also after longer periods. Symptoms generally have subsided within 2 to 3 months after discontinuation of metoclopramide. Avoid REGLAN injection in patients with Parkinson’s disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms. If treatment is unavoidable, use REGLAN Injectionfor the shortest duration of treatment and periodically reassess the need for continued treatment. Routinely monitor for signs and symptoms of Parkinson’s disease.

Motor restlessness (akathisia) has developed and consisted of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. If symptoms resolve, consider restarting at a lower dosage.
Neuroleptic Malignant Syndrome
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 REGLAN Injection 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:

Immediate discontinuation of REGLAN Injection and other drugs not essential to concurrent therapy (see PRECAUTIONS – Drug Interactions).
Intensive symptomatic treatment and medical monitoring.
Treatment of any concomitant serious medical problems for which specific treatments are available
…

PRECAUTIONS
Additions and/or revisions underlined:
Hypertension
In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; avoid REGLAN Injection in patients with hypertension or patients taking monoamine oxidase inhibitors (see PRECAUTIONS – Drug Interactions).
There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. REGLAN Injection is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Discontinue REGLAN Injection in any patient with a rapid rise in blood pressure.
Fluid Overload
…
Adverse Reactions with Rapid Intravenous Administration
Intravenous injections of undiluted REGLAN Injection should be made slowly allowing 1 to 2 minutes for 10 mg since a transient but intense feeling of anxiety and restlessness, followed by drowsiness, may occur with rapid administration.
…
Anastamotic Dehiscence
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Effects on the Ability to Drive and Operate Machinery
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8 Use in Specific Populations

Pregnancy

Additions and/or revisions underlined:

…

Fetal/Neonatal Adverse Reactions

Metoclopramide crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with material administration during delivery. Monitor neonates for extrapyramidal signs.

Nursing Mothers

Additions and/or revisions underlined:

Metoclopramide is excreted in human milk. C Monitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia.

Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of REGLAN Injection has been established as a single dose to facilitate small bowel intubation in pediatric patients in whom the tube does not pass the pylorus with conventional maneuvers.

The safety and effectiveness of REGLAN Injection has not been established in pediatric patients for the following:

relief of symptoms associated with diabetic gastroparesis
prevention of nausea and vomiting associated with emetogenic cancer chemotherapy
prevention of postoperative nausea and vomiting
to stimulate gastric emptying and intestinal transit of barium where delayed emptying interferes with radiological examination of the stomach and/or small intestine.
…
Geriatric Use
Additions and/or revisions underlined:
Metoclopramide is known to be substantially excreted by the kidney, and the risk of adverse reactions, including TD, may be greater in patients with impaired renal function (see WARNINGS – Tardive Dyskinesia).
…
Other Special Populations
NADH-Cytochrome b5 Reductase Deficiency
…
CYP2D6 Poor Metabolizers
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 REGLAN Injection. Avoid REGLAN Injection in patients who are poor CYP2D6 metabolizers. If use in unavoidable, monitor for adverse reactions.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

Additions and/or revisions underlined:

…

Tardive Dyskinesia and/or other Extrapyramidal Reactions

REGLAN injection may cause tardive dyskinesia or other extrapyramidal symptoms, parkinsonian symptoms, and motor restlessness. Instruct patients to immediately contact their healthcare provider if symptoms occur. See WARNINGS.

Neuroleptic Malignant Syndrome

Serious neuroleptic malignant syndrome (NMS) has been reported in association with concomitant treatment of metoclopramide with another drug associated with NMS. Advise patients to report all prescription and over-the-counter medications to the healthcare provider. Instruct patients to seek medical attention if symptoms occur.

Depression and/or Possible Suicidal Ideation

Symptoms of new onset or worsening depression as well as suicidal ideation have been reported in patients taking metoclopramide. Instruct patients to contact their healthcare provider if any of these symptoms occur.

Drug Interactions

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. Advise patients to report all prescriptions and over the counter medications to the healthcare provider.

Effects on the Ability to Drive and Operate Machinery

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.

MEDICATION GUIDE

Additions and/or revisions, please refer to label for complete information.